#Excitotoxicity

[blueoaknx]

Mitochondrial Dysfunction Drives Cognitive Decline

Introduction

Mitochondria, often referred to as the powerhouses of the cell, are crucial organelles responsible for energy production through adenosine triphosphate (ATP) synthesis. Beyond their well-known role in energy metabolism, mitochondria regulate a wide range of cellular processes, including calcium homeostasis, reactive oxygen species (ROS) generation, and apoptosis. When mitochondria malfunction, the consequences can be far-reaching, especially for energy-intensive organs like the brain. Recent research highlights mitochondrial dysfunction as a central factor in cognitive decline, contributing to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. This article explores the mechanisms by which mitochondrial dysfunction impacts cognitive function and discusses potential therapeutic strategies.

The Brain's Energy Demands and Mitochondrial Function

The human brain, despite accounting for only about 2% of body weight, consumes approximately 20% of the body’s energy. Neurons, the primary cells of the nervous system, rely heavily on mitochondrial ATP to sustain synaptic activity, ion gradient maintenance, and neurotransmitter synthesis. Efficient mitochondrial function is critical for maintaining neuronal health and connectivity, which are foundational for learning, memory, and other cognitive processes.

Mechanisms of Mitochondrial Dysfunction in Cognitive Decline

Reduced ATP Production: Mitochondria produce ATP through oxidative phosphorylation (OXPHOS) in the electron transport chain (ETC). Damage to ETC components, often caused by genetic mutations or oxidative stress, can reduce ATP production. Energy-starved neurons may fail to maintain synaptic function, leading to cognitive impairments.

Excessive ROS Generation: While ROS are natural byproducts of mitochondrial activity and play roles in cell signaling, excessive ROS can damage mitochondrial DNA (mtDNA), proteins, and lipids. This oxidative damage exacerbates mitochondrial dysfunction, creating a vicious cycle that contributes to neuronal degeneration.

Impaired Calcium Regulation: Mitochondria help buffer intracellular calcium levels, which are critical for neurotransmitter release and synaptic plasticity. Dysfunctional mitochondria may fail to regulate calcium, leading to excitotoxicity—a condition where excessive calcium causes neuronal injury and death.

Mitochondrial Dynamics: Mitochondria constantly undergo fission (division) and fusion (joining) to adapt to cellular demands and maintain their integrity. Imbalances in these processes can result in fragmented or overly fused mitochondria, impairing their function and transport within neurons.

Mitochondrial Transport Defects: Neurons have long axons and dendrites that require efficient transport of mitochondria to regions of high energy demand, such as synaptic terminals. Dysfunction in mitochondrial transport mechanisms can disrupt synaptic activity and contribute to cognitive decline.

Mitochondrial Dysfunction in Neurodegenerative Diseases

Alzheimer’s Disease (AD): Mitochondrial dysfunction is a hallmark of AD. Amyloid-beta plaques and tau tangles, characteristic of AD, have been shown to impair mitochondrial function. Elevated ROS levels and reduced ATP production exacerbate neuronal loss and cognitive decline in AD.

Parkinson’s Disease (PD): PD is associated with mutations in genes like PINK1 and PARKIN, which regulate mitochondrial quality control. Impaired mitophagy—the process of removing damaged mitochondria—leads to their accumulation, contributing to dopaminergic neuron degeneration and motor as well as cognitive deficits.

Huntington’s Disease (HD): In HD, mutant huntingtin protein interferes with mitochondrial dynamics and function, resulting in energy deficits and increased oxidative stress. These mitochondrial abnormalities contribute to the progressive cognitive and motor decline observed in HD patients.

Diagnostic and Therapeutic Approaches

Biomarkers of Mitochondrial Dysfunction: Advances in molecular biology have identified potential biomarkers, such as altered mtDNA levels, ROS, and metabolites associated with mitochondrial pathways. These biomarkers can aid in early diagnosis and monitoring of neurodegenerative diseases.

Pharmacological Interventions:

Antioxidants: Compounds like coenzyme Q10, vitamin E, and MitoQ target mitochondrial ROS, reducing oxidative damage and preserving mitochondrial function.

Mitochondrial Biogenesis Enhancers: Agents like resveratrol and PGC-1α activators promote the production of new mitochondria and improve mitochondrial health.

Calcium Modulators: Drugs that stabilize calcium levels, such as memantine, may protect neurons from excitotoxicity.

Gene Therapy: Gene-editing tools like CRISPR/Cas9 offer potential to correct mtDNA mutations or enhance the expression of genes involved in mitochondrial quality control. For example, boosting PINK1 or PARKIN expression could improve mitophagy in PD.

Lifestyle Interventions:

Dietary Interventions: Ketogenic diets and intermittent fasting have been shown to enhance mitochondrial function by promoting efficient energy utilization and reducing ROS.

Exercise: Regular physical activity stimulates mitochondrial biogenesis and reduces oxidative stress, offering neuroprotective benefits.

Sleep Optimization: Adequate sleep is essential for mitochondrial repair and the clearance of damaged proteins, such as amyloid-beta.

Future Directions in Research

Understanding the interplay between mitochondrial dysfunction and cognitive decline opens new avenues for research and therapy. Emerging technologies, such as single-cell transcriptomics and advanced imaging, allow for detailed exploration of mitochondrial dynamics in neurons. Additionally, the development of mitochondria-targeted drugs and nanotechnologies holds promise for precise therapeutic interventions.

Conclusion

Mitochondrial dysfunction plays a pivotal role in driving cognitive decline and is implicated in the pathogenesis of various neurodegenerative diseases. Addressing mitochondrial health through targeted therapies, lifestyle modifications, and early diagnostic measures offers hope for mitigating cognitive impairments and improving quality of life. As our understanding of mitochondrial biology deepens, so too does the potential for innovative treatments that could transform the landscape of neurodegenerative disease management.

[helenwhiteart-blog]

On oxalates, glutamates, autism and DNA

As alluded to in another post last month, I was recently forced to reconsider whether many if not most of my ongoing issues of increased pain, sleep issues and more are related to ongoing issues with oxalates (a topic I covered in a post a couple of years ago at the point I first found out about, and began to tackle them in my diet). Without repeating myself, oxalates are anti-nutrients found in…

[thefactsofthematter]

not to nerd out on main but i fucking love mnemonics

[z-nightshade]

orv x aoo incorrect quotes pt.2 BC yeah.

Han Sooyoung: so... How long does the human body stay alive after decapitation?

Chopper: Decapitation is quickly fatal to humans and most animals. Unconsciousness occurs within seconds without circulating oxygenated blood. Cell death and irreversible brain damage occurs after 3–6 minutes with no oxygen, due to excitotoxicity.

Han Sooyoung: *Quickly scribbling out notes*

---

Zoro: So they call you Demon King of Salvation, huh? But they call me the King of Hell, so doesn't that mean you're my subordinate? *Is secretly very curious as to why but has too much pride to ask*

Kim Dokja: You wish, algae boy. *Is also secretly very curious as to why and has too much pride to ask*

---

Yoo Joonghyuk: *Is kind, cares about people, wants to save the world, wears a long billowing coat a cape!*

Luffy: OHMYGOD!! A REAL LIFE HERO WOWOWO JOIN MY CREW!!

---

In addition, Yoo Joonghyuk being very giddy about being called bro by Franky but hiding it.

Kim Dokja and Han Sooyoung joining the Sunny D Cassandra fanclub book club and finding some very familiar stories being written out along with great original works.

Cass in the corner: this is so embarrassing wtfff >///<

Han Sooyoung: I'm surprised you didn't question me asking that

Chopper: *thinking about all the unhinged medical questions Cass has asked him in the past* It's not the weirdest question I've head

Cass: *watching these two idiots jump around asking each other what they want to know and face palming. They know that they'll have to be the one to explain for anything the get done* Why can't people just voice out their wants and desires?

(hypocrite)

Luffy about Yoo Joonghyuk: Wow!!!! Cass look!!! A real life hero!!!!

Cass: I know! Isn't he cool!

Yoo Joonghyuk: *brooding silently bc he doesn't know what to do in front of such open and genuine admiration*

Yoo Joonghyuk and Cass are both mentally melting into goo in the corner for very different reasons. It's just more obvious to tell that Cass is bc they look very dazed and flustered whenever someone compliments their writing

[unification]

it's significantly easier for me to think today, i think i've worked out a little combo for when post sickness neuroinflammation hits:

i took 15mg dxm + 2mg naltrexone last night. usually i feel out of it several days with dxm, but not this time. i'm guessing it's because of naltrexone blocking my mu + delta opioid receptors. this is huge for me, the reason i put off taking dxm when my pots+csf/me gets bad is because i don't want to be unable to think clearly for the next few days also applied a 17.5 mg nicotine patch. i've been using these for a while now but haven't posted about it. basically nicotine activates neuronal nicotinic acetylcholine receptors which regulate microglial activity (resident immune cells of the CNS) inhibiting secretion of proinflammatory molecules and upregulates glutamate transporters enhancing glutamate clearance from the synapse and reducing excitotoxicity.

[nixmcretro]

Me, Myself and Progesterone

I touched on progesterone (P4) in my last transgender update post. I am not quite sure if progesterone is working in the way I want it to. My biggest annoyance with it is feeling like my brain is on fire just before trying to sleep.

Rewind to late February 2024, for almost three weeks my progesterone dose was doubled to 400 mg of oral, micronised, compounded progesterone – 200 mg twice a day. That’s up from the 200 mg once at night.

I had also ceased finasteride. And finasteride interferes with the progesterone (oral) pathway conversion to neurosteroids such as allopregnanolone. This is because finasteride blocks *most* of the activity (~70%) of the 5-alpha reductase (5AR) enzyme. In turn, reducing levels of allopregnanolone – or at least slowing their conversion to neurosteroids.

My sleep quality has been pretty broken for a while now. Look at those orange blocks. And here I was looking forward to some of the benefits from progesterone. Anxiolytic? Yes please! Sleep improving? Definitely!

Instead I get this whole brain fire thing and feel like I’ve taken an anxiogenic. That got me thinking, brain on fire? Throw in some formication and it’s what feels like a glutamate rebound or surge. Excitotoxicity perhaps?

I’ve experienced similar feelings while withdrawing from pregabalin (decreases glutamate levels) and trusty old diazepam (increases GABA levels). Definitely that same feeling though. It appears that taking what I would consider a small dose (2 mg) of diazepam negates the insomnia pretty well. Even though diazepam isn’t a terribly good choice for sleep. It takes me from being a wired insomniac to sleeping beauty in about an hour.

Another interesting side effect I am seeing a lot more of is dissociation. Ordinarily, I would only experience this while in high stress, high anxiety situations but recently I’m noting it a lot more just doing chores around the house – which is a little concerning.

Regardless, it seems that something is messing with my GABAergic system and metabolites of progesterone fit the bill. Armed with my two-thirds of a biomedical science degree I went digging for more information on the metabolites. Up above is an image from my last health blog post. Note the action of finasteride on progesterone – blocking allopregnanolone (THP) and isopregnanolone.

I wonder if moving to a more potent 5AR blocker, such as dutasteride, would reduce the side effects of a higher dose of progesterone? A question for my endocrinologist I suppose. I restarted my finasteride to at least partially block some of the following progesterone metabolites. Let’s look at the metabolites a little closer and how they act.

Allopregnanolone (Tetrahydroprogesterone or THP) Positive allosteric modulator 9 hours

Pregnanolone Positive allosteric modulator 1 – 3.5 hours

Isopregnanolone Negative allosteric modulator 14 hours Targets allopregnanolone only

Epipregnanolone Negative allosteric modulator Half-life unknown

Alright, so a bunch of neurosteroids are doing a bunch of things. A few are being blocked, but also produce negative side effects when they weren’t blocked. Hormones are messy. Where does that leave me? I guess I am left questioning whether I should be taking progesterone at all. At minimum a dose reduction is definitely called for. I will probably return back to 200 mg and see what symptoms, if any, follow.

My search revealed some interesting data with overlap in symptoms shared with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) in cisgender women. 

PMDD is believed to be caused by fluctuations in gonadal sex hormones or variations in sensitivity to sex hormones.

If sensitivity to level shifts is reason for the negative side effects, then single or even twice daily doses are probably not enough to smooth out the levels of neurosteroids for me, allowing me enter a withdrawal state, perhaps? Brain on fire? This paper offers some great insight into the mechanisms behind it all with some interesting side notes on SSRIs.

Interestingly, SSRIs increase allopregnanolone levels in the brain, rapidly and at low doses, as demonstrated in rodents as well as in patients with depression.

Could this be one of the reasons why I can’t tolerate SSRI/SNRIs? At the very least, it’s some food for thought. Worth noting that the original study has been questioned a little further along in the paper. Let’s circle back to those progesterone levels again. From Wikipedia

Progesterone levels tend to be less than 2 ng/mL prior to ovulation and greater than 5 ng/mL after ovulation.

What were my most recent levels again? 9.1 nmol/L or should I say 2.6 ng/mL (freedom units). That’s at 200 mg once daily at night, measured in the trough. I really need to ask myself, do I want to have symptoms of PMS/PMDD? Is that even a question that needs to be asked?

Looking at the levels on Table 1 in this paper give an idea where my levels line up. If you factor in the short half-life of most of the metabolites, once daily dosing is probably a bad idea. Ideally, I should look into getting the dose split to 100 mg twice daily.

Of course I have to be mindful of negative risk such as the androgen backdoor pathway. This has the potential to generate unwanted androgens like DHT – which will affect the hair on my head. That’s why the finasteride is here to stay until most means of testosterone generation is removed from my system…

It’s not all bad though. Finasteride competes with progesterone for the 5AR enzyme – which results in even less 5AR being available for testosterone -> DHT conversion. Another point worth considering is that progesterone has a positive effect on bone-building cells (osteoblasts). This can help with avoiding or reducing effects of osteoporosis.

Touching on side effects I’ve noticed, Progesterone should increase libido. Which is something I do not want due to past trauma. However, I wonder if the finasteride side effects are at play here. Again, I don’t consider them negative side effects either.

Other oddities I’ve also noticed my facial hair has become darker at the higher progesterone dosing at 400 mg. My upper lip now has dark black hairs, that’s new and unwanted. It might be useful for IPL treatment. But now there’s shadow on my upper lip I never had before. It isn’t just the thinning of skin either. The hairs are black instead of blonde.

One big uncertainty is that I’m not sure what my levels of estradiol will be at the next blood test. Are the 200 mg of pellets doing their job properly? Or did they fail? Does the dose need to be increased?

For now, I’ve been supplementing the implant with the remainder of my 2 mg estradiol pills while the pellets stabilise. One pill gives me ~85 pmol/L in estradiol levels. I’ve only just ran out of those so now I’m adding in some of the estradiol gel (Sandrena branded). These gave ~200 pmol/L estradiol per dose according to my most recent blood tests. In theory with one a day, I should be guaranteed to be in the late follicular phase – regardless of the implant levels.

Anyway, that was one heck of an info dump. I think that sums everything up that has been on my mind lately.

TL;DR 400 mg oral progesterone makes my brain go on fire. Progesterone metabolite levels shifting around are very activating for me. I will now target cisgender progesterone levels in the late follicular phase. Hormones are complicated. One size fits most seems to be at play when it comes to progesterone. Nothing like some trial and error! 🙃

[common-misconceptions-daily]

Alcohol does not necessarily kill brain cells.[737]Alcohol can, however, lead indirectly to the death of brain cells in two ways. First, in chronic, heavy alcohol users whose brains have adapted to the effects of alcohol, abrupt ceasing following heavy use can cause excitotoxicity leading to cellulardeath in multiple areas of the brain.[738] Second, in alcoholics who get most of their daily calories from alcohol, a deficiency of thiamine can produce Korsakoff's syndrome, which is associated with serious brain damage.[739]

[butchrupertgiles]

ok post cancelled because the notes are. deeply annoying. but im getting the last word:

- msg allergies are not real they have never been clinically proven.

- if msg allergies were real, 'no added msg' would not be an allergy warning. this is because overactice antibodies don't care if the allergen is 'added' or just in the food. this one has been so overlooked I can't tell if you didnt read the post properly, or just don't have food allergies and don't get how they work. also, have you noticed this doesnt happen with any other allergen? like, rocky road or trail mix that doesnt have peanuts doesnt say "no peanuts" in a big rosette on the label.

ok on to the researched bit:

- 'msg symptom complex' is called that because people self-identified msg as the exposure causing their symptoms(1). However, clinical studies failed to find a link between msg consumption and 'msg symptom complex' in patients who self-identified as reacting to msg. there is *only* anecdotal data for this. (source)

- in the 1990s the US FDA commissioned FASEB to investigate the possibility of a danger in msg. the only test that returned evidence of danger was making subjects consume 3 grams of msg with no food (typical addition of msg to food is 0.55 grams) (source)

- The study indicating a link between aspartame, msg, and fibromyalgia symptoms had a sample size of 37. This was reduced to 31 because six subjects saw no symptom benefit from the aspartame-msg exclusion diet. (source) The msg challenge dose was 5 grams, for 3 consecutive days, which is a very extreme amount, with a condition that is known to be exacerbated by dehydration (msg does contain sodium. less than table salt but still.). The study also relied on a theoretical basis of excitotoxicity, which means too much glutamate in the diet affecting neurotransmitters. However, in a diet containing msg normally, msg would be a small portion of glutamate consumed daily (0.55g from msg, 13g from food). (source).

- As much as I looked, I couldn't find any real data that demonstrated msg was more prevalent in asian foods than other cuisines. it is present in east asian cooking, yes, in particular in sauces and marinades, but its unclear how this compares to, for instance, italian food, which uses tomato and parmesan cheese extensively (both of which contain significant amounts of MSG). (source) It seems like the link was made because MSG was first isolated by Japanese chemist Ikeda Kikunae. Notably, China and Japan are different countries with different cuisines, although the stigma is primarily attached to Chinese food, stemming from a 1968 letter published in the New England Journal of Medicine that was, again, entirely anecdotal and based on one patient's self-identified exposure (whenever he ate Chinese food) and speculation (MSG is the ingredient causing this reaction). (source)

The long and the short of it is every issue people report with MSG is either attributable to the generally high sodium intake of people who eat a lot of takeaway food, or the nocebo (2) effect, either from knowing they're consuming MSG specifically or from assumptions about Chinese food containing an exceptional quantity of it. Yes, even your mother who swears she's allergic. Even your cousin who swears he gets the sweats from Chinese food. They might not be lying - the nocebo effect is a powerful thing and a high sodium diet isnt great for you (although msg can reduce sodium intake if it replaces table salt, as it requires less sodium for a similar flavour benefit) - but they are wrong.

(1) also its called that because msg fearmongerers worked out the name "Chinese restaurant syndrome" made them look racist and insane

(2) the placebo effect's evil twin

if i had no added MSG i wouldn't be proud of that. i wouldnt advertise it

[nshtn]

Wesker is a man of no half-measures whose risks are calculated. You are one of his finest researchers, growing on him like a moss.

He should reward your hard work in his name, shouldn't he?

You reach bubbling, dangerous fever pitch when you ask him to indulge a little fantasy of yours - good doctor, bad doctor... unfortunately for you, he has much grander, lavish ideas than that. He also has every chemical substance manufactured in the last thirty years at his disposal.

This is a trust fall, and Wesker inflicts the rise and the plunge; will you sink or swim? Do you trust him with a butterfly needle?

11.6k, tags: medical - medfet;dubious science experiments;gloves;iv / needles;labcoat;pharmacokinetics, intox - consensual aphrodisiac;fantasy drug, nsft - blood;biting/marking;dom wesker sub reader;edging;sadomasochism;overstim;penetration, themes of obsession, PW(much)P/reader uses gn pronouns & female genitalia - technically an in-universe 'continuation' of Mind the Gap.

1st fic of C Complex. | 2nd | AO3

This had been planned for longer than you could think of – in some way, at least, floated as an idea that had become more and more coherent the longer you knew the mysterious virologist until you found yourself sitting in a medical bed somewhere within the confines of your workplace, closed off from the rest of its’ office-spaces and lab-units.

You’d thought that he’d use the opportunity, when you’d first brought it up, to bully you, but instead he’d made a tentative hum and raised his pointer finger to his chin, shades trained on you as a single eyebrow arched with the heady temptation of the power that he’d hold over you if he did it.

God… you trusted him with that? To play God over you in his own right? To take the reigns of your mind – to inject you with a drug, far above pharmaceutical standards, and use it as an aphrodisiac while maintaining your consciousness?

You were very stupid or very brave, or, the third option: very desperate. He found that his thoughts warred over which of the three you presided on – surely, you had at least some awareness of the truly terrible amount of blood that stained his hands, so what made you trust the world’s best virologist (...and phlebotomist – Excella not withstanding) with decommissioned medical equipment and TRICELL’s finest supply of Cellegelyn Hydrochloride?

Was it because you trusted him with something far more superficial – your daily dose of medication – though he’d show you the swirling liquid each time? He wouldn’t now; oh no, he’d leave it in the air and see if that would make you squirm a little.

With the perceived safe danger of it. With the thoughts that would cloud your mind, and your own reaction to them. Oh, he’d prepared – he was no man of half measures.

Filthy minx. He supposes you did tame him, however – his violent urges spared you, replaced with an intense need for you to provide him stress-relief when you were within his presence. The self control it took not to run tongue over bare skin and bite when he was stressed out of his mind… you knew, didn’t you, little devil?

L-deprenyl. Enantiopure from Deprenyl, unnecessaries trimmed for your body’s convenience and your mind’s sanity – you were getting the best of the best, something that wasn’t even considered marketable. He wasn’t looking for your complete, stolen submission under the duress of a sunken mind; he wanted your willing, pleading submission handed to him as the MAO-B affinity bled into MAO-A. The infusion system would drip-feed your pliant, greedy vein far past the tipping point of a pharmaceutical dose.

In theory, this would be a slow build-up and the ride of a lifetime – literally, considering the inflictor. The excitotoxicity, though, was fine-tuned compared to the sledgehammer of a much rougher, barbaric chemical that prodded dopamine, serotonin, and norepinephrine out of unwilling receptors mindlessly... Oh, no, this was measured; this would trigger within the context of the situation. If you didn’t want it, then it wasn’t going to force your hand. And that was the real magic of it, wasn’t it? To see you squirm with how badly you’d want him to control you… to watch you beg for his touch, for more, for less; it hardly mattered, he just wanted to feel the rawness of your need – as long as you wanted him.

Only him, though.

Perhaps that was what made you desire this so strongly from him specifically? You could’ve asked someone else, but you’d delegated it to him.

You were always quick to fluster when he’d do anything that might tease at the seams of your mind and unfurl the fringes of your deeper feelings – you weren’t very good at hiding them, no. But that was something so appealing about you: undeniably book-smart even to him, yet your social defenses were lacking in the thickness of your mask. Your cheeks would pop with color at the slightest provocations – when he’d compliment your papers or handwriting, when he’d inject your thigh and run his nitrile-gloved fingers exaggeratedly over your bare skin, when he’d pull his labcoat’s arm up to his elbow and you’d watch, hungry-eyed and slack-jawed, at the way his veins shifted and his muscles tensed as he depressed the plunger of a syringe, bead at its’ tip swelling with the threat of spilling.

What an interesting little specimen… distracting thing. He was surprised he had yet to spill anything – a testament to the degree of his precision, he supposed. You’d make for a fine subject in testing the true unchained abuse potential of L-deprenyl.

Really, you should thank him for what he was about to do to you. There was a lot of other things he could do rather than fuck his finest researcher hopped up on a harmless discontinued psychostimulant. He had to admit it, too: he wanted you under him, surrendering and breathless, with a ferocious depth even he had not yet come to fully understand. None of the pieces of his set were intended for what he was about to do with them – it was its’ own breed of blasphemy, but something in that made his cock stir with the event that would transpire.

That Wesker would inject you and fuck with you until you were little more than a puddle that didn’t know what you wanted. Fucked-out under his touch, quivering and moaning long after his hands and hips would cease. Fuck, you’d be so cute like that.

And you couldn’t help it – there was an incredible intimacy in the needles he’d sank into your skin. You’d done them first, but then he’d took an interest and all-too-conveniently chided your skills in rotating your spots. Then he’d taken over for you, and it’d really only been downhill in the sheer depth of your bludgeoning crush since then: you had come to find that there was a radical intimacy he took to when he did it, always a sort of deftly placed respect for the needle he used as if a reverent tool, lack of clinical detachment clear in the way he’d languish in your squirming.

You kept coming back. You weren’t that socially maligned – he figured you must’ve liked it. Liked the attention, liked the gentleness from a man who could snap you. Yes, you liked when he played nice. And he had to admit it: you were remarkably tolerable. Or, at least, you’d grown to be.

That gave him pause sometimes. Since when had he grown so soft for another? It didn’t matter, though, did it? Who would stop him – Spencer? Marcus? Their precious Doctrine? Ha. No. Only their ghost. And he’d vanquished the idea of that when—

You were just… you were stubborn like that. An extremophile of your own, well aware of the danger and lambasting yourself in his presence regardless of blaring, bleary red. Though, after all, he’d hired you as a temp and you’d turned it into a permanent position through the deathly combination of your brains and your unwitting, accidental charisma. You reminded him of someone he used to know – someone who had been a lab partner, too... but you were soft where that man had been hard. You didn’t seem to hunger for power at all – you just wanted for connection, for knowledge (and he could’ve said that about the man he’d known at one point, too, but their lifetimes had corrupted them both beyond the grasp of a simpleminded humanity) – and Wesker could give you these things as easily as he could breathe.

No, it wasn’t hard to be a chameleon to someone who barely cared whether you even wore the mask these days. He dreaded to admit it to himself, but you were terribly, awfully, horribly amicable. Maybe that was a negative observation – to get along with him? Did you possess a superego? Oh, what was he saying – of course you did. Yours was just better than everyone else’s, like his.

Anyway, your daily injection was just your medicine, nothing more than a routine with a sprinkling of powerplay from him – but now? Now it didn’t have to be. Now he could take it to the next level.

You tap your leg against the bed with an air of mild impatience. You’d like it better that way: he could stop pretending he had any degree of detachment. He wasn’t any more subtle than you. Did he think he was?

A shiver of anticipation ran up your spine as Wesker approached, light gray labcoat, black turtleneck, black pants, distinct lack of a tactical belt a sore thumb in his appearance and what he had planned as he leaned his frame into your personal space.

“Hello there,” he punctuated, simply. His gloved fingers reached out and two digits slithered from the edge of your jawline to the fat of your neck, where they pressed in your soft flesh until your chin tilted to meet the intensity of his gaze at an odd angle. It wasn’t entirely comfortable – though perhaps that was intentional. “Are you… ready for your treatment?” A statement more than a question – and dripping with sin you both knew, thin veneer of professionalism no cover.

So very abrupt, though. You’d have to adjust.

“Oh, yes, Doctor Wesker,” you quipped back, finding it somewhere in you – heart thumping a beat faster – to bring your hand up to settle at his chest. He’s far quicker than you with his own, grabbing your sluggish wrist in his hands, a sliver of skin peeking from his labcoat and muscles taut with the strength of his grip. “Ah ah ah,” he tuts, chiding gently as he lets your hand down at your side, “touching is my job. You wouldn’t want to render me jobless, would you?”

In any true professional environment, this would shatter his medical license irrevocably. And yet… and yet, with this knowledge, you huffed a laugh and a hot, bothered breath in one. “Of course not.”

Wesker responds with an appraising look, gentle upturn in the corners of his mouth approvingly. “Good. Good.”

A moment of silence passes as he cases you, adjusting his shades, letting them drift down the bridge of his nose with the aid of gravity until he’s certain they’ll nearly fall off. You sit up a little in the bed as he lets go of your jaw, fingertip slinking away. Then, he removes the offending pair himself, tucking them in a breast pocket when it doesn’t go as he planned.

No matter – that magmatic gaze is fully trained on you, now, no degree of separation from which to cloak itself in. Both parties run deep with unspoken desires, it seems.

“Any doctor will tell you that all operations start with preparation of the patient,” he begins, smile dripping away into a natural disguise of cool neutrality as he reaches behind your bed and pulls a holter monitor out, placing it on your stomach and bending over you – your nose filling with the oddly compelling scent of dark, earthy-sweet vetiver, black orchid and the sanitized dichotomy of ozone – to fetch three leads.

You bring your hands out to help him, but his free hand darts out to them, warm glove brushing your digits to remind you to still yourself silently.

You flush a little. You’re not used to this level of Wesker’s unbidden attentions or this degree of enforced helplessness – and it was only going to become more prominent as the night passed. You’d expected a little when he’d unexpectedly agreed to this – but he’d really… he’d gone above and beyond your… your simple idea.

Loyal to a fault, you raise your arms above your head and he pulls your gown up, chest exposed to cold and bare air. Goosebumps raise as he trails his fingers ever-so-lightly, gaze trained on your soft, supple, easily-broken skin. He makes a noise of further approval as he attaches the leads to the holter monitor and slips one under one breast, the cold sinking in and making you shiver a sound of your own that makes you clear your throat.

How uncouth. He hadn’t even gotten started and your tiny mind was already his playground.

“So eager,” he croons out-of-character, voice low and dripping timbre and a little grit as he places the other cold lead.

The third has his hand sliding with an indecent slowness up your bunched fabric, deliberately placing the last of the leads high on your chest so he can swipe his wandering digits across the canvas of you.

“You want this treatment, don’t you?” It’s consent wrapped in the easily-swallowed pill of his role as the good doctor.

But, god, how you wanted the bad doctor to come out.

“Yes, I’ve…” you quibble, “I’ve wanted it for so long.” You avert your gaze with a shyness one part real and two parts theatrical. You should’ve been an actor, the way his eyebrows twitch from their normal cinch a little before they settle again. To pull that out of a man who prided himself on his degree of control… or to know that he laxed his walls around you… both contributed equally to the reverence that had him hanging the stars in your eyes.

Like a tiger that bared its’ teeth upon you but never truly bit down. A monster of a man in the palm of your hands, offering some hidden facet of himself for you to cast your adoration upon.

The trust alone from the closed and thorny mind of a razor-sharp intellect could make you moan a little. You instead tilt your head at him, and Wesker’s vision creeps up into your own. If you were truly guileless, you might’ve thought his lens contained a degree of insecurity with the weight of your silent affectations, like you might not like what you’d find.

As if this meant something to him. You cast it out of your mind – there’s no way. But perhaps you don’t notice that he stiffens and then relaxes with a breath a little too deep.

“You’re going to get it, don’t worry,” it’s a sultry hum, and he’s holding down the power button on the device laying on your stomach until it powers on. Three lead mode. He’d even charged it. Damn.

You both fall into a comfortable silence as he turns on the infusion system – a TC Atlantis, a collection of many features in one and no doubt a climbing expense to license that was pristine and unblemished by the horrors that it was steeped in – and sets it to 80. You wonder to yourself the degree of what this machine has seen in its’ time, what stories it would tell if it could. The flow it’s set to seems slow...

You trust him with it out of necessity. You lend him the same trust he’s lending you in this moment, and perhaps you are a fool for it – but that’s part of the fun, the not explicitly knowing. You squirm a little, pressing your legs together with the intention of drawing him from what he’s doing.

Wesker’s hand strays from the machine, now set, to your leg, giving it a curt pat as he returns dutifully to it. You still caught him, but he was nothing if not a careful and well-disciplined man.

But the wisp of warmth that swirls around in your abdomen curls and inflames as Wesker hooks up a harmless bag of saline – with a little potassium, he might add – to the machine, hitting a setting at the bottom before he turns to you. “Now, just let me fetch your… analgesic,” he offers, a stumble in the search for words that fit his current role as he briefly reaches out for your hand and gives it an ever-so-polite squeeze.

You flash him a knowing smirk. “Take your time,” you reply gently, though you both know that the wait is torture.

The virologist stalks off momentarily with the sound of his black boots clicking like heels against the pristine, sanitary tile, and you are left to stew in your curiosity. A frown tugs at you. The Atlantis is set to a custom name instead of what it should really be, merely labeled ‘pain relief’. That must’ve been what he’d been gently tapping in.

Is the effort a matter of pride? It seems like so much.

You look around you and it all truly sets in as you curiously bring your arm up to you, careful not to disturb the holter monitor – a mean eighty six beats per minute and a wonderful ninety eight percent saturation – as you move the bracelet with your fingers, admiring his work. It’s an admission bracelet to a fake hospital, but your name, birth date, weight, eye color, and gender are all perfectly correct – and he’d never taken birth date or weight from you. Something about that makes the curl of warmth in you tighten a little. The stakes increase – the danger – and what you know he knows.

About… about you. What else does he know? The unknown fills itself with contextually relevant info that makes your cheeks burn a small deal before he’s even done a thing. How did he get that information?

But Wesker returns before you can continue to dwell beneath the surface of it. You let go of the bracelet before he can notice, your curious eyes searching the small bag and insertion needle – its’ tip as small as he can afford to go, a butterfly needle a nicety in the name of your creature comforts.

“Which arm?” he says, leaning forward and right back into your space a little. You mock up a ‘hmm’ before you offer the one closest to the Atlantis. The damn bag had its’ label removed. Some part of you feels outclassed by this and demands brattiness to make up for it, but the threat of getting stuck wrong has you on your best behavior. “This one, please, sir,” you drawl.

He tosses a glance straight at you, eyes teeming with a darkness to their gaze that sends a shiver down your spine. Do you know? Do you know the fire with which you are constantly playing with? You stoke a flame you can’t hope to vanquish, you lovesick fool… but he doesn’t voice the projection he’s heaped upon you.

He doesn’t compress it either, curiously – but it drains away nonetheless as he breaks two of his fingers from one of his black nitrile gloves, fingers breaching the material. He pulls an overly-convenient isopropyl alcohol pad from his labcoat and generously rubs the tips of his fingers with a bit too much attention and panache before he brings the same pad to your offered inner arm, sliding it entirely from there – “Do you prefer insertion… here?” – all the way to your inner wrist, where he rubs it a little more insistently until your mouth goes dry, massaging the alcohol in – “or here?”

God, he plays with his food, doesn’t he?

And he plays so well, so gently, little circles against the sides of your wrist as your inner nerves adjust to his touch, making your body twitch a little. So pliant, so easy that he can’t help himself… “I-I don’t-- I don’t mind,” you stutter, flexing your fingers a little as he brushes against such sensitive, smooth skin.

That makes him let out a huff of a laugh with a short pause.

Still so eager – even now. The lamb walks to slaughter itself… “The veins here are easier to see,” he lies coolly, pinprick cat eyes casing your reaction and the splotches of telltale color that rise in you at it. Aren’t you an odd one? His pointer finger brushes it intently, rolling it back, and forth, and back, and forth along the tendon it sits, pushing it down a little like a tensile cord in faux demonstration that makes your breath hitch.

Fuck, you really are a devil. Are you a masochist?

“It responds very well,” Wesker adds, then, emphasis on ‘very well’ as his gaze falls back to real concentration as he fetches his needle, one extra dab of alcohol at your wrist for extra-extra-sure as he uncaps it. You hold your breath. He holds the needle close to your hand. “Don’t ball your fist – that’s schlock.” Ah, Wesker always used such… odd eloquence – old and regal. Apparently, according to him (he’d told you, at least) Umbrella taught him a lot of them. But it’s befitting of someone with his status, somehow. Right now, he’s both antagonist and protagonist. “Mhm,” you nod, keeping your arm still.

He stops, then, free hand wrapping around the side of your arm that faced down to trap your wrist in place as his other hand closed in with the needle, those slit eyes of his intently calculating where to stick you to get a clean hit. Or if he even should – if he should intentionally miss and dig and see if you squirm, or how much of a social misstep it would be to selfishly indulge in his own sadism.

But he chooses not to play with an unknown variable, giving a little huff at his unspoken desire to make you hurt so well before he leans in a little more. Then, like that, he strikes – it’s over swiftly, needle breaking your tender skin and ravaging the vein wall. A tiny click sounds out as the sharp is disposed, and a tinier tube that leads out is the only remainder of the action.

...huh? All that lead up and… “Wow. That was… I didn’t expect that,” you say, blinking a little despite yourself. You can’t help it – you expected it to be more… more painful. He chuckles, and it morphs at its’ tail end from something lighthearted to painfully dark.

“Perhaps I should forget a little,” is all the doctor offers you from the unwoven threads of his thoughts, deep and wizened by the ports he’s placed in times past. “Would you like that next time, my patient?” You give a tiny gasp as the situation is re-acquainted with you, the elusive ‘my’ making your brain twirl. It doesn’t mean anything, of course it doesn’t, but it’s another part of a grand set aimed at the warmth slowly spreading through you. “I think you could s-stand the humbling,” you shoot back, smirking.

Alas, he brings reality into you by pressing a little on the insertion point, which causes you to instantly cringe with the uncomfortable digging sensation. Ouch.

“Hm? What’s that?” he purrs out, smug, and he does it again as an experiment, viperous eyes digging past your own with unrestricted glee. You suck in a breath and hiss through it, but his other two fingers are applying enough pressure that trying to pull your arm away won’t work without injury to the wall itself. “Fuck, that is an odd sensation,” you growl out, eyelids crinkling.

Wesker chuckles. It breaks off into a manic, deep bark of a giggle that is somehow as much powerplay as it is oddly, inescapably genuine. You’re… your facial expression simply caught him – like an ant with light bearing down on it or… or something. He’s in control of the situation, he can spare the emotion, he reasons away.

“What a dirty mouth,” he says. And before you can object, he leans forward and your lips brush – then meet – a quick, chaste kiss before he pulls back. “Mm. Spreading your disease,” he quips, shaking his head a little at his own virologist humor. That one could use a little more tinkering, he thinks.

“A-Ahuh,” you say, eyes lidding a little as you move your head forward just enough to try and re-capture his thin, soft, frustratingly far lips. He punishes you for your greediness by reminding you of his grip on that fucking point and, in spite of yourself, you moan a little, and then your horrified expression nearly kills him again.

“So responsive,” he croons, belittling, letting go of it entirely before he gets carried away; he doesn’t want to collapse anything. Then again, he could restick your other arm...

But you can tell that he’s reluctant. You can nearly smell it on him – a shark that has snagged its’ tooth and barely restrains the desire to really pull. “It was the kiss,” you pout, eyebrows drawing together with a pitiful look that is befitting of your current position, if anything.

“Hm. Of course. Typical,” Wesker asserts. He might not even be joking – “Just how many kisses do you dispense on average, doctor?” You quirk one of those pity-brows.

He regards you, blinks a little at your comment, seeking its’ intent. Then, he relaxes – you’re not the jealous type. No, not like he’s becoming. The thought of your lips on anyone else’s makes him want to grab your shirt and make you the outlier. But, he has to admit it: you’ve already become a statistical anomaly in his world…

“Hmm. One or two, if I’ve deduced that they’re susceptible,” he admits, and the honesty surprises you. It makes sense, though – he’s married to business, but he’ll do what business demands to make deals.

You nod a little, nonchalantly.

The fire seeks to burn you, though – he seizes your shoulder instead of your shirt and presses his lips to yours again, a little more insistent. You gasp and he pulls back a little, but then he’s back on you, and you’re surrounded in his delicious scent, and he smells quite macabre like black orchids warring with the isopropyl and too much hand sanitizer, and it’s odd but beneath it all you can smell the diluted day’s sweat of him.

That makes you have to bite your own cheek not to chase the contact when he breaks it again, finally satisfied with having painted a more dazed expression on you.

More pressing matters await than the continuation of discussion, though, and Wesker forces himself to focus on something other than his urge to take and taste the object of his own bud of crawling, itching desire.

“Now,” he says, breaking the moment, “time to begin treatment.” He sounds a touch breathless and it makes the corners of your mouth turn up a little. Not so unaffected now, huh?

He looks back to the TC Atlantis and moves from nearly leaning into you to adjust it. You watch as he fiddles with the bag he’s got. He produces a small syringe – no steel tip this time, rubber – and attaches it to the end of the bag, pulling back the plunger with two fingers until it’s filled with a measure of white, unassuming liquid.

What could it possibly be? You hum a little, eyes narrowing. Knowing the man you’ve come to acquaint yourself with, it could be nothing but more saline – or it could be something insane, like… like ketamine. Or something like that. You hope not – that’s a bit much for you.

Wesker picks up on it, though his red slits remain focused on what he’s preoccupied with. “Having second thoughts, little lamb?” This new addition makes you swallow and avert your prying eyes. “I’d hope not,” he adds, a little darkly, “it’s a little late to be turning back, don’t you think?”

Because you won’t be, not soon, he thinks. But he doesn’t say that.

You churn with an eccentric mixture of sudden illumination to your situation and a surge of lust. No escape… Your breathing gets a little heavier and the corners of his mouth turn up. “I understand that this is hard for you,” he assures, though he’s put on all the theatrical professionalism of a patient’s advocate, “but please,” it drops from that into something serious as his eyes turn to yours, smile falling, “don’t worry – I’m an expert.”

And Wesker says it with such courage that you just nod. You are in too deep now. But, god, it feels good to be surrounded.

He pulls the syringe out, satisfied, and lines it up with one of the branches on your IV, screwing it in. Before he begins, though, he stops. “Are you ready?” The way Wesker says it, slow and dragged out, is as if you will be hit with something dreadfully strong. The calpain potential makes you tremble lightly.

“It’s… it’s nothing truly insane, right?” You look to him for safety, and he shelters your mind with a scoff, as if the mere notion escapes him. “Of course not. I am interested in how you’ll fare with it, though,” he admits, one hand brushing your hand to impart his presence. It’s shockingly intimate, somehow.

It’s also all you need to be bewitched by such a dangerous, cunning, calculating man. For all you know, this is a sick trap and you’re crawling onto his sacrificial altar. What if it’s… what if… but then Wesker’s making unbroken eye contact with you as he pushes on the plunger, looking at your eyes for anything, and you greet that with a whimper that makes him smile a little. It climbs into a very toothy little smirk, one canine peeking as the final Cellegelyn in the syringe disappears in you.

But you don’t feel different, and you blink. Do you have some kind of immunity? “Um…”

He doesn’t respond, he just nods a little, as if he knows, and he adjusts the bag and the speed of its’ draining �� he sets it up to mix with the saline on 100. That’s… a little quicker. “Mm, we’re just getting started,” he says, hint of something predatory emerging as the seconds eclipse.

You gulp and chuckle nervously. “Am I supposed t-t-to… to feel any d-different?” You can’t help it – you feel a tug of disappointment at the lack of anything noticeable. “Not necessarily. Not yet. Patience, patient,” he chides, holding a single gloved finger up at your worried protest. Wesker does something a little more like when the two of you are alone rather than as a doctor; he leans both of his arms against the side of your bed – which would, in your shared lab unit, be his chair, usually – and regards you.

There’s a sort of artificial softness imbued there. Is it weird if you find his effort endearing? It should scare you. You can, at least, cast out the thought that he somehow got his hands on a dose of uncharacteristically gritless Progenitor-based-something. If you’d mentioned your concern he would smack you, and you’re sure of that, too.

He interrupts to ask you a question. You see it, now – the desire behind that cold, creeping gaze. I want you, it says. He’s quiet, almost a silver, electric whisper. “What do you want?” It’s so charged.

You quirk a brow, but then you let the statement wash over you. What do you want? To continue. But what do you want? “I want you,” you say, nodding with certainty. He smirks, brows drawing together at that in approval.

“That’s it,” he compliments, and then he puts a hand on your stomach, brushing up and up your skin.

You shiver as he does. It feels… very nice. Then, he dips it beneath your gown again and traces over the leads he’s placed, hand climbing higher very slowly as he appraises you. The texture of the glove, warm and clinical, makes you huff. And then you whimper, and he gives a little ‘oh?’ and continues, dancing his fingertips along your sternum before he draws his hand back down, down, down, against your thigh, tips of his prim and proper nails brushing against your skin.

It feels really good – really, really good, and it makes you arch a little. Oh. “That… that feels n-nice,” you qualify, and your free arm twitches as it attempts to reach to him to guide him.

You stop yourself.

He doesn’t stop himself, though. He gives a tiny tug to that catheter with his free hand and you crinkle so beautifully as the sensation climbs through you, moaning a little, drawing your thighs together and clenching them gently – so helpless, so adorable. And all his to play with, now.

Putty.

“Struggling, lamb?” Wesker chuckles accusingly, letting go and sliding his hand up your arm instead, the touch erupting fresh goosebumps across your skin and making you lean into it as if starved. “Whatever you gave me is- is… y’know,” you avoid, beginning to flush more.

His touch is a lot – but it’s not enough, you want more. He chuckles a little more as you shoot him a very desperate glance.

“What ever happened to patience, hm?” But even as he says it, Wesker is sliding his hands over you and grasping at your grabbable hips, making you shift to allow him better access. “Feisty,” he breathes, digging his digits into them. You moan pathetically – the sensation is enhanced, spilling out from your hips and feeding your core like a direct connection you didn’t know you dialed. “T-That’s… nice…” you comment, eyes wrenched shut as you surrender yourself to more sensation.

The TC Atlantis clicks and filters more into your vein in the background. Everything is starting to feel like a pleasantry, just a little bit better than it should be – even just background noise that fills your ears, almost… musical.

Wesker acknowledges you with an affected sigh as a hand dips nearer to the corner of your thigh, massaging the flesh with deft, experimenting swipes of his fingers. You buck a little trying to encourage him to where, optimally, you’d prefer him, but your insistence is met with his resistance. “Not yet. But… soon.” He’s a little lax because he notices your eyes have dilated significantly.

You mewl in return, pleading at him – “How soon?” – and buck your hips a little.

“Soon,” Wesker repeats, a bit more snippy and sharp, letting go of your thigh a little hesitantly. You miss the warmth of it, your own desires laid bare as your brows press up together pleadingly even without the prosody of your speech.

He pushes down the bed’s arm and leans forward, then, forcing your lips against his own. It’s surprisingly sweet and needing of you, like the more he notices that you’re falling under the Cellegelyn, the more of himself climbs out from his chest.

From his shell.

You’re hopelessly addicted to that, grasping, perhaps, at the ghost of what you perceive as closeness, moving your lips on his own, digging your hands into the sides of your bed so you don’t try to lean forward to grab his – because you know, cognitively, that the intimacy will get you punished. He massages the pads of his thumbs at your hips all over again, hard,kneading sensitive flesh to the point of bruising as his tongue laps at your lower lip, and you open your mouth obediently, if sloppily, letting him in with a yelp.

Letting him all in. God, please. You moan into his mouth at his grip strength and you swear he drinks it in. You are massaging his ego so excellently. What an entertainment. He’s surprised at how fast it’s kicking in – aren’t you just dearly receptive? Some kind of polymorphism or something, perhaps? What a malleable little oddity.

Wesker’s tongue rolls against your own and even now, you notice it – it’s longer and leaner than a normal person’s, pressing into your wanting mouth with the strength of his need as you moan again into his own. He swallows the sound down, lips synchronizing with your own pair only enough that your mixing saliva doesn’t spill from you. You’re forced to swallow because you’re producing so much, and the sensations running through you make your legs furl and whimpers spring from you.

Your face is cherry red, and he stops kissing you to let you heave breaths in with a satisfied sound, only to nudge his nose up against yours in a tease before he leans back the rest of the way.

Wesker, of course, lacks the same embarrassing composure-drop – aside from a string of hair that peeks forward and the way his labcoat leans over your legs, he’s still perfectly normal. How frustrating. “And…” he sucks a breath in, himself, “...and how is the treatment progressing? How do you feel?”

His eyes are trained on yours, searching as he thumbs your hips with apparent absentmindedness, no longer the grip he had before, sparingly. Those pupils are so intense – and they always have been, but they’re even more intense now. They also gleam a little brighter, something you take great interest in as the cue that he’s feeling something and you’re not alone. It makes sense that he wears his shades so often, because without them, those eyes – and how bright or dim they are – are peepholes into a grander being.

You look a little dazed, but you manage to swallow a bit more, clear your throat and speak through the warmth that clamors through your guts, pawing insistently at the seams of your mind. It’s odd – your wits, you find, are still about you – at least partially. You don’t feel dumb. Perhaps you feel loose, but you’re not out of control. Everything just feels so good, and everything that makes you feel makes you feel so much.

You squirm... you’ve been doing a lot of that. It makes Wesker smirk with a self-satisfaction. “I-It’s going very well, d-d-doctor Wesker,” you reply, though you sound far more affected than you mean to. Or is that just the perfect representation of your slow, marching unraveling?

“Mhmm...” He stops crowding your space and pretends to immerse himself in thought, his voice deep and telling. Then, one of his wispy brows raise. “And what could I do to assist you further, hm?” His eyes flit to the holter monitor as he speaks. The way he looks at you, next, is suggestive, but it belies that you’re obviously not allowed to breach the unspoken rules of this game and beg him to fuck you.

Not yet, at least. There is time until the Atlantis has completed its’ infusion – the bag isn’t nearly empty. This doesn’t mean you can’t pathetically beg for other forms of contact, however.

So you puff a little and think really hard, and sustain your blush and roll your hips with the power of your powerlessness… “Please, I just… I just want you on me, just… touch me, p-please?” You look down, very ashamed at the way you sound and yet hopelessly turned on, and it makes Wesker’s eyes glint dangerously.

Your defenselessness is truly delicious. He really ought to keep you. He can imagine it, a fantasy he almost certainly cannot partake in: you in his lab, leashed and collared to his side, where he can take a break whenever he so feels the whim chase him to touch you. And you, whimpering and needy at every turn, always ready to give and give selfless stress relief like a good toy. So utterly human.

It should disgust him. Instead, your specific breed of naive humanity is like a fetish. You’re not bound to the ghost of a Doctrine, you’re not infected with any virus; your DNA is unblemished, untouched like a tap of pure, rippling potential. You’re so corruptible… and yet… and yet he cannot find it in himself to do that with any real, consequential permanence. God, he wonders if you’re compatible with… no, no, no.

Your moans would be a pleasant background chatter as he compares different strains under electron microscopes though, he thinks, instead of your mindful chattering. And you must see it in his eyes, the way they flare up as they gaze into your own with a deathly precision, because your spine feels a shiver climb up it and you let out a shaky whine.

You’re beginning to need him so badly that the emptiness in you aches.

“Keep talking,” he urges, one of his gloved hands shifting to slide over the fabric of the front of his pants, the other sliding over your body, seeming to really focus, with honed calculation, on the parts of you that draw the most sound from your throat.

You feel so lit alight with sensation this time that you writhe under him as his other hand draws, deliberately, over your sides – “Oh, g-god, why does it feel so- so-… hmmah,” – over each rib, across your hips and the outsides of your thighs, where he presses his digits inward teasingly as your core tightens – “F-f-fuck, Wesker, please, please,” – under your gown, which he bunches up and unbuttons to expose you to the air, making you whimper pathetically amidst the cacophony of your own groaning, his gloved fingers, two bare, pressing into your chest and your sternum and wrapping around your neck. You suddenly feel like you’re going to––

Wesker pauses. He’s leaning over you, gray coat draping across your legs, watching your face intently.

Like he’s looking at an anodized experiment encased in a tube. So clinical, cold, and utterly transfixed by the exponential disentanglement of your mind. Your psychology entrances him, laid bare and leaking.

Your eyebrows bunch up and a look of betrayal crosses you, and then you pout – embarrassment is far away in another land, you were so... “Don’t- don’t- why did you s-s-stop?”You almost feel like you’ll cry, bucking your hips incessantly into nothing, nothing at all. Since when had you been moving them? “Don’t stop, please, oh, please, p-please,” you prattle on, breathing shallowly. His grip increases a little and it falters.

“Why?” he asks, voice rough with need and accusatory, though he’s well aware of the answer – he just wants to force it out from you under the duress of all that dopamine, serotonin, and norepinephrine. Oh, yes, it’s long since leaked from one to another. But, fuck, you’re making him want to give in to his own basal urges and fuck you hard into the bed.

But he has more control than that. Plenty more restraint than you currently possess. It isn’t time yet – he knows what he’s doing. And when it is, he’s going to ruin you...

You actually sniffle. “I was so-- I was so c-c-close,” you manage to stutter out, your eyes seeking out his with a drugged desperation that makes his cock throb. “Is that so? … Really?” Wesker’s grip on your neck releases a little, and you lean your head and press the tiniest, defeated little kiss against the gray cuff of his labcoat in your addled confusion.

It releases completely and you swear he chuffs at you. “Well? Keep going, then.”

He slides his hands across your shoulders and dips them across your chest, digs them underneath your back and runs them along the sides of you. “Oh, thank you, thank you,” you babble breathlessly. You arch so beautifully, so wonderfully pathetic, and you sing and moan for him.

“So responsive,” he croons, “so powerless against me. Against the slightest little touch…” He demonstrates it by wrapping them across your stomach, pushing his hands deftly, each finger trailing themselves across each of your ribs in a dizzying pattern, each movement making you twitch and whine. So pitiable – such a far cry from your book smarts.

“Doesn’t this embarrass you?” But he knows it doesn’t – not now.

You can feel the lust in the coils of you tightening and pulsing with his touch like electric lightning. He dips one of his hands between your rolling hips – “Ohhhhh, yesssss,” – finally, middle finger running over you, and your labored breathing gives into rhythmic cries as you gush all over his hand, arching. “Wesker, oh, god, Wesker, oh, oh, fuck, f-f-fuuuuuuuckkkk, W-W-Wesk– Wesker… hhhhhah, ah, hhah, ah...”

He keeps it there, wriggles his digits about a little as you cry out so prettily for him. He keeps it until your gasping and moaning of his name (something he deigns for you to stop doing, such music to his ears) become the tortured rasps for him to stop. “Oh, GOD W-W-Wesk– Wesker it’s TOO much- T-TOO much,” you hiccup, legs pressing together, body writhing around even as he strokes you, sadism very clear in his catty, agitated gaze. “Please! Please, no m-m-more, no more, no more-more-more Wesker, W-Wesker, ple-e-eaaaase,” you beg through your teeth, free hand grasping at the other arm of the bed with a white knuckle grip.

Should he really give you mercy? You’d continue to say his name, a nice ring coming off your lips. “And here I thought you wanted me to touch you,” he muses, mock complaint going unheard to the higher regions of your mind. Your voice is as pretty begging to stop as it is to go… decisions, decisions… and he’s so indecisive, really, as you wriggle helplessly and squeak, dribbling even more on his fingers. It’s such sweet, embittered torture to your electrified nerves.

But then you start to cry, tears rolling down your cheeks as you plead and plead, and he ceases, stilling his hand but never pulling it away. “Fine.” It’s said sharp and final, but his expression is amused. The glove between your legs is covered in you – sticky strands that make the nitrile glisten wetly, truly a sight to behold.

His mouth is awfully dry. How lucky for you that you’ve got a bag of saline to keep you company. All he has is a heaping dose of your saliva.

You thank him breathlessly as you come down from your high, finding that it takes an abnormally long time. You’re so dizzy. Your body feels like it runs with pleasure in your aftershocks like an almost-painful livewire of lightness, your chest puffing so much and so quickly that the holter monitor – which has migrated to the side of the bed by now – beeps about your low oxygen saturation.

Wesker quirks a brow, his smugness wiped away at it and replaced with a little frown. He yanks his hand from you, which makes you stiffen before you relax, jelly-like, and he rips off his gloves, one of his hands finding your own to hold. “Easy, now,” he chides. But you want to yank your hand away – it’s so sensitive, and this is oddly intimate, so you twitch and whimper and...

The already-quirked brow climbs higher as his free hand pauses the TC Atlantis.

Wesker certainly thought that you had some kind of oddly strong reaction, but he hadn’t expected it to be to this degree or this fast – perhaps there were secrets to your mind he had yet to uncover about its’ inner workings? Things that your medical records simply didn’t divulge because nobody had ever looked. Intriguing. “Breathe with me, alright? In and out,” he splays your hand against his chest, underneath the fabric of his labcoat and over his turtleneck. Your hand slides a little, admiring even in your daze as you follow his command wordlessly, the holter monitor finally ceasing its’ siren.

“Good. Keep going, I’m nowhere near done with you,” he admits, humming a little from deep in his chest to occupy you away from his words save for the command inlaid. You continue, and eventually you find you’re no longer dizzy.

“So…” the virologist begins, his hands grasping your own to place it back on the bed, then darting away as if the potential connection scares him off – especially when your brain is lit alight with so much oxytocin. Your hand twitches after his, but then stills. This is Wesker, and this is a scene, not a normal man and a warm bed – but you still appreciate what you perceive as aftercare.

“How are you feeling now?” It comes out a little awkward, something that you’ve not quite heard from him in a long time, like he’s a little unsure of himself. You reckon he is, the way his eyes keep flitting to the monitor and then you, though when he notices your noticing he forces them to remain on you.

But he’s not terribly empathetic – he’s still roiling with arousal, evident in his own budding impatience.

“Better,” you nod, giving a weak smile as you shiver with a particularly strong aftershock.

He kicks off his boots very suddenly and climbs onto the bed with little grace, sitting on his knees and between your legs, once more regarding you. When you gasp, he gives a cocky, toothy grin, the predatory streak in them returning full force, no longer pressed down to comfort you. “What, did you think that was it? That I was going to make you cum without internal stimulation and let you free?” He giggles – and then it turns into a chuckle. The chuckle turns into a sadistic cackle of a laugh that shakes his shoulders.

“Oh, no, little bambi, you’re very far from home,” Wesker says, eyes narrowing with a mean look as he leans in to steal a little of the saline he’s been loyally feeding your vein. He grabs your jaw harshly and you squeak in delayed surprise as he pulls your chin forward and down, tongue relishing in the taste of you together as it tangles in your own dominantly, suckling and pulling sound from you as he lets his first clipped moan out.

You take the opportunity to swallow it and he forces your head back and against the bed for your attempt, lips so tightly packed against yours that you squirm under him.

He lets you up on his own time, pulling back as you cough and heave breaths in. Everything is so much right now that you already feel like he’s been touching you again, your hips twitching. It isn’t unnoticed, especially when your legs are flowing around his knees. “How convenient for me, you’re already ready again…”

“...but I suppose I’ll be a gentleman,” he croons, stroking his own ego as he pulls another pair of nitrile gloves on with a snap that makes you weak, tightening your knees around his waist as you hoist yourself a little in preparation. Just the feeling of shifting them makes you pant for a second – you’re fried.

“P-Please?” You shiver with anticipation and say the first thing that comes to your mind. You don’t know if you’re pleading for him to be easy on you or to prep you, honestly. You might be dripping wet, but you do need a little prepwork before he just s—

Wesker’s fingers are at your slit again before you can continue to dwell on it, his gaze tilting down and his brows furrowing in concentration as he experiments with your sensitivity, thumbing at your swollen clit a few times. You suck in a breath and your hips twitch – “A-ahhhh, god,”– and he parts his knees more to force them apart. That makes you full-body shudder, your hands grabbing at the cloth of his labcoat and squeezing it when he begins to move his thumb in a circular motion, other fingers sliding against your slit, one slicking itself up and driving into you.

You moan as he works it in and out of you in calculated strokes, eyes flitting from the holter monitor, your face, your glistening, fluttering hole. He grits his teeth and huffs, breath hot, face beginning to get flushed – something you realize even in your haze that you have never, ever seen before, the sight before you making your back arch and your fingers curl. He doesn’t quite realize that it’s his own appearance – debauched in his own way – that set you off, and he sets to hammering his finger in you with forceful insistence to make way for another digit.

You quiver and buck your hips disobediently, and you know you’re really in it now because he doesn’t even respond except to grunt, eyes narrowing as they land on you in meaningless warning before they refocus on your fluttering grip.

Fuck, you’ve got suction. He had expected Cellegelyn to loosen you up like a muscle relaxer, not leave you gripping his finger like you’re trying to milk it. You’re so goddamn hot, you know that? To debase you like this – to steal your intellect away and leave you the weak one writhing beneath him… it could become an addiction if he wasn’t careful.

Maybe all the little powerplays he’d pulled had been intentional to get to this very point. Had you ever considered that? Had you? “You have no idea what you’re entertaining, doll,” he growls.

The pet name, completely unexpected and new in the moment, makes you heave. Doll? “W-What?” you squeak, staving off the curdles of warmth that threaten to overwhelm you all for the sake of his own satisfaction and the potential at more of that. Oh, you’d be so good – you’d be the best doll, anything to keep this going. “F-Fuck, Wesker, feels so-- so good,” you mumble, barely coherent.

His nostrils flare at your damaged, telling cadence, and he slows his pace, which only makes you squirm a little more trying to force up some friction.

The squelching sound of your utter arousal is driving him mad. He needs to bury himself to the hilt in you sooner rather than later, lest he pop the button on his pants. The strain against them is starting to hurt, and the discomfort only serves to fuel him as he pushes a second finger in you, ceasing his thumbing so that you don’t overload before he’s got a chance to comfortably seat himself in your pink, blushing warmth.

You curse at the second insertion, but you stretch with beautiful ease. Your hands, though, are gripping his labcoat enough that it’s actually starting to pull him a little closer. You can smell him, and you can smell his cologne again, and the sensation of his fingers driving into you is making you whimper. Everything is crackling through your entire body and you want to curl up in a ball and hold onto the sensation for as long as you can. You sink your teeth into your lip to try and silence yourself even though it feels so good it’s almost burning with each deep stroke, and you bite yourself so hard you bleed.

You’ve released blood in the water.

The scent of copper tang makes him growl inhumanly, and his free hand doesn’t bother to disrobe of its’ filthy wet nitrile, wrapping around your back and pulling you forward with an unexpected strength as he continues to press into your walls with his other, tongue lapping along your lower lip and teeth lewdly. It makes you whine – it burns so good, and everything feels so good, and you white knuckle his labcoat as he lets go of you, shoving you back.

“Nghh, fuck, Wesker, I-I-I won’t––”

“No more fucking games,” he interrupts, shaking his head and puffing strands of hair out of his sightline. You nod, unable to answer him properly with your mouth. He’s beginning to lose his mask and his patience, and he fiddles with the button of his pants and pulls down the zipper, freeing himself.

You encourage him as he pulls his digits out, and you whine at the startling lack-of, greedy hole still clenching around the air. He wastes no time, smearing your natural lubricant over himself in pumps that make his mouth hang open enough for his elongated canines to be seen.

You let go of his labcoat and bring your hand to your mouth, biting your fingers to keep from babbling about how gorgeous he looks. But then you tear them away. It must be known, even at great personal cost, because how many people get to see him this way? Has anyone ever even told him? To bare another second in this world without him shouldering this knowledge will kill you, your addled mind is certain.

Or maybe it’s just the oxytocin surging through your veins and demanding you bridge minds. But you cannot deny yourself, consequences be damned.

“Y-You’re gorgeous,” you breathe, eyebrows raising in total earnest. You look so thoroughly smitten that he can’t help but lock eyes with you, and his very own fate in pretending this is merely a scene is ruined because his cock visibly throbs in his grip at your honesty.

He diverts his cat-like eyes, long lashes fluttering. Like this, he almost… almost looks bashful. Tendered. You nearly forget the situation before you feel his hot tip at your entrance and practically choke, so wet and bothered that it slides right in and he groans in turn.

“God, you’re still so tight,” he praises, ignoring whatever happened seconds ago, one hand gripping your hip, the other on the side of your thigh.

“You’re f-f-fucking… beautiful,” you say, eyes wide and blown out completely. Before you can continue your tirade to ruin his appearance of detachment, he punishes you by tightening his grip painfully, his cock driving into you to the hilt as you scream for a second. He curses alongside you, the noise surprising him, barking it out in equal at the way your walls quiver as they take him.

But he doesn’t tell you to stop…

It’d be more noticeable if you weren’t desperately trying not to cum, thoughts difficult for you to grasp and direct as your nails dig into his labcoat. Urge was easier, but you wouldn’t deny him this now; not after he’d treated you to such an experience prior.

He picks up on it by the way your walls move around him, incessant, and he growls low, long and deep as if to force your body to submit to his demand to hold off. “Not yet, I hav-haven’t… had my fun,” he commands, chest expanding with a labored breath.

He’s wide, and it makes it all so much worse – no, so much better. You ball your fists until crescents are digging into your hands as he pulls back and then rocks forward a few times, each one making you whimper at its’ peak, and your whimpers only serving to further ingratiate you to faster rocking.

Wesker’s grip on your hip tightens as he rolls in and out of you smoothly, wet slapping filling the air. Skin-on-skin. His gaze finally returns to you. “Know what? You’re the fucking pretty one, taking me so well, fuck, I want to… hhah, keep you like this,” he babbles, both his hands gripping your hips tightly as he fucks your taut body back and forth on his length with the ease that Progenitor bestows upon him.

What he gets in return – the prize of your reply – is your broken moan tearing through the air. You’re leaking out of yourself, hardly capable of remembering your own name, less and less of it all springing to you with each successive thrust.

To be privy to such power makes your core pulse.

You’re trying so hard for him, but you can’t help how your body grows impossibly tighter, beginning to lose your grip on thought as you mumble. Your vision crackles with the weight of his throbbing length pistoning into your soft, gracious heat.

“Mmmah’gnna, g’nnaahh-hhahh,” you slur, trying desperately to warn him, your hands patting and grasping at his sides to convey the spirit of your meaning.

He just keeps going, spilling noises that match your own incoherence against a wall of unintelligible complimentary ramblefucking you never could’ve expected from such a cold man. “Mmnhh, sofuckinggoodforme, you gonna be so– FUCK, fucking good for me, huh? Gonna k-keep you, hnnh, gonna fucking keep– keep you– make you m-m-mine, allmineallmineallmine…” His prosody blears around the edges and tightens when he drives into you, slurs when you milk him and leaks emotion around seams that can no longer bare to keep themselves together in lieu of his frantic fucking. Cellegelyn was the best fucking choice for this he ever could’ve chosen, and he’d do it ten times over to feel your heavenly grip crushing the day’s stressors away.

He’s a genius.

Hopefully you aren’t paying attention to what he’s actually saying enough to see the startling, alarming bright red – and if you are, which he severely doubts (and even he is having great struggle to pay any heed to your admittance that you were dangling on the edge) you’d discount it as lustful rambling.

But your head is lolling, tongue out and panting desperately as your orgasm crashes over you for the second time tonight. Your pulsing, dribbling, gasping warmth hugs his in a rhythmic pattern, head drawn back in a silent scream as one hand pulls at your own hair with the intensity that bombs your nervous system with each quick, deep, hard stroke he’s mindlessly, mechanically performing.

He leans forward, suddenly, breath a hot gasp, mouth hanging open as he seeks your neck.

Wesker diverts only enough to avoid incidentally murdering you, lax mouth – and each glittering, monstrously inhuman canine shaped by something truly ancient you couldn’t hope to understand on the level he did – sinking into the tender, sweet flesh of your shoulder like the strike of a viper.

You cry out and he groans into your shoulder as his hips finally give way to stuttering as they fuck too deep and too quickly into your overstimulated heat, and then he paints your insides, one arm seeking your side to death-grip as his other digs his nails, intentionally, into the flesh of your hip, drawing blood as his hips jerk and he bottoms out in you with each hot spurt.

You feel so good squishing and squeezing around him, you’re such a good hole.

You’re still twitching as he pulls out of you, releasing your shoulder from his mouth only after gnawing into it a little more – which makes you sob and sniffle and kick and moan, your body transforming the pain into otherworldly pleasure beyond your understanding.

“Nnnnh… ooohhhh, ohhh goddd,” you breathe, legs shaking as your abdomen leaks a heady mixture of the two of you.

So fucked out... what an adorable, pleasant look on you. Or is that the hormones talking? Wesker doesn't dedicate the time to dissecting it, he lets it wash over him in the way his face – and brows, more notably – take on a certain rare peacefulness, an expression they don't normally occupy.

You can do nothing but watch, no strength to intervene as Wesker’s tongue licks languidly at the wound he’s made, rolling over the beads of heme-rich blood that leak from you, teeth stained with your essence and breath tainted with the scent of iron. No drop of his mark is left to waste – it is almost ritualistic, though some small corner of your mind clinging to sanity whispers that this isn’t something he normally does.

It’s not quite cuddling – more like he’s trapping you against him, though he’s polite enough to prop himself to the side to avoid crushing you underneath him (that’d be rather unfortunate). This doesn’t mean he ceases his mindful lapping, continuing despite how you wriggle a little beneath him – if anything, he seems to find amusement in countering it.

He’s let go of your hips and lessened the grip on your side at some point, though you don’t quite register when.

It altogether reminds you of a big cat with a carcass, licking and gnawing idly to pass the time, more than it does the cuddling and afterglow you’d associate with what followed sex. But, strangely, you find that you… enjoy it. Not fucked out enough to attempt real affection, your hands come up to grip themselves in lieu of your desire to grab one of his. He seems to understand this, an unexpected and gentle hum that rises out of his throat, deep and low and claiming, his degloved hands – when did he take them off? – smoothing the gown you’d nearly discarded over you, shielding most of your naked body from the world around it, though not your shoulder.

He smells a little like you and you smell a little like him, a mix you find endearing – one you believe you may not soon forget, wonder in the back of your mind on the debate of whether or not he’ll commit this to his memory, too. Did he have a snapshot memory? His intellect would lead you to believe that he might.

The sensation of his slender tongue against the bite makes you struggle not to let any more sounds escape you, breathing elevating a little with each gentle lave – but you struggle, more truthfully, not to make a feeble attempt to shove him off of you; there’s absolutely no way you’re going to be able to cover the rich, deep bite unless you wear a scarf. And everyone… everyone will know who bit you with the shape it’s made.

Wesker knows that, too. He’s indulging in the thought of it, actually, knowing it will inflame – and maybe cleaning the blood from it with himself rather than the third party of an alcohol wipe is a little more alien than it is human, a hunger for heme that is satiated by your very own supply. Dangerous, though, because it’s not the first time he’s tasted it from another person – though it’d never been under this context, he supposes.

How all of this plays out for your future working with him – working under him, next to him, that is – he’s certain it’ll lend itself to his finer manipulations very well, in fact.

You wonder yourself, vaguely, more in concepts than words, how long he’s going to be cuddly before he resurfaces as the cold, emotionless figure he presents to the world and stalks off. You didn’t take him for the type to stick around, so to get anything at all after the conclusion shocks you in a pleasant – and perhaps a bit thoughtful with the weight of implication – way.

“H-hi,” you say, vocals shaking a little as you begin to come back down from it all. Wesker’s throat bobs, chest puffing with the edges of a laugh at your greeting, as if waking from a dream. Conjugation still threatened to escape you.

He stops cleaning you and lays his head in his hand, magnificently dulled gaze boring into your own. “Hello,” he replies, clearing his throat to shake it of the blood that clings, swallowing the last of it, tongue licking his lips in savor of you. The sight kicks up the dust of your blush again, having recently calmed.

When did he tuck himself away? He looks entirely clean – and you, on the other hand, are an absolute wreck.

“Enjoying yourself?” Wesker chuckles impolitely, brow cocking at your disheveled appearance and the catheter still wedged in your wrist.

Oh… that’d have to come out. You give a curt nod, sit up (with one hand as your guide, which still feels awfully sensitive) and look around you for something to stem the inevitable bleeding when you pull it out.

He tilts his head a little, watching you.

“Do you need something?” It’s both smug – as he is the only one who can provide it, really – and truthful, as he’s not quite sure your wits are totally about you to be pulling on anything. So, as your free hand moves to your wrist, he reaches out and grabs it.

“I’ll take care of it,” he swiftly decides, voice gold-lined with what little of the natural and yet uncharacteristic softness remained. After all, you seem amicable to it.

You blink as it washes over you. One event would unfold after another, and your brain would process them all individually. This painted an odd dichotomy you allowed yourself to steep in if only for the coddling it provided: you can think, but it’s hard to speak. The remnants of a dissociative? But you certainly remember the experience.

“O-oh, okay,” you softly say, reply delayed by your condition and the gears in your mind that cowed to his purposefully gentled tone.

Wesker gingerly turns your other arm over and retrieves a bandaid – though you feel more than too old for those, the situation demands it of you in your clumsiness. He runs his digits along the area and kneads a little at the thin tape holding the catheter down, then knits his brows as he pulls it out in one swift motion, replacing its’ presence with a bandaid that he holds down with frightening strength, quite a bit more than is necessary, perhaps because he must curtail the urge to lave at that, too.

You close your eyes tight and his brow quirks. “You’re still that sensitive?” Then, the virologist leans in a little, a conspiratorial hint in his tone. “Could you be… exaggerating?” But he leans back out with an edge of playfulness and ease, almost showy, rather than caution or anger.

“No,” you shake your head, opening them once it’s over. He hums thoughtfully.

The time has come for Wesker and you to depart, and he shuffles around with the meaning to stand before your hand sluggishly tugs at the cuff of his coat. He turns to face you, though you see that he creeps with a subtle impatience.

“Just wanted to say… t-thank you,” you cough out, pushing yourself into a sitting position and stretching your legs as you mean to stand.

Your belongings were bagged nearby in a themed tote. The man had truly thought of it all.

He considers something for a moment, seeking beyond your words, before he relaxes his shoulders and stands up, dusting himself off with the intention to stalk away.

“Don’t thank me yet,” he chides, slit pupils glinting with something you cannot define that surpasses the weight of the red flags you’ve seen before as he turns away, perhaps intentionally, unclipping his shades from his breast pocket and pushing them up entirely.

Wesker begins to walk away. “Thank me when you understand the depth of my generosity…” - a line that you find climbs up your spine, but he adds one last bit as he rounds a corner, clack of his boots with his disappearance to clean up - “...or the consequences of it.”

(thanks for reading this massive 11k!! lil aftercare tune soup for your soul:)

[joncawleynews]

Cerebrolysin: Side Effects, Benefits, and Safety

Cerebrolysin is a prescription medicine derived from porcine (pig) brain tissue. It is marketed as a neurotrophic agent, meaning that it promotes the growth and survival of nerve cells. Cerebrolysin is used in various countries worldwide, primarily for the treatment of neurological disorders like stroke, Alzheimer's disease, dementia, and traumatic brain injury. However, the use of Cerebrolysin remains controversial due to its origin, potential side effects, and lack of strong evidence for its efficacy in some conditions.

Cerebrolysin is a neurotrophic agent derived from porcine brain tissue, used to treat various neurological conditions.

It is thought to work by promoting the growth and survival of nerve cells.

While its use in some conditions like stroke and dementia is supported by some evidence, its efficacy for others, like Alzheimer's disease, remains debatable.

Cerebrolysin can cause various side effects, including allergic reactions, nausea, headache, and dizziness.

The safety of Cerebrolysin in long-term use is unclear.

Due to its origin from animal tissue, it poses a potential risk for transmitting infectious diseases.

Always consult a healthcare professional before considering Cerebrolysin therapy.

What is Cerebrolysin?

Cerebrolysin is a prescription medication made from a hydrolyzate of porcine brain tissue. It's a complex mixture of peptides, amino acids, and other biomolecules. The exact mechanism by which Cerebrolysin works is not fully understood. However, research suggests that it might act by promoting the growth and survival of nerve cells through various pathways, including:

Neurotrophic activity: It enhances the synthesis and release of neurotrophic factors like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are essential for the development and maintenance of neurons.

Neuroprotection: Cerebrolysin might protect nerve cells from damage caused by oxidative stress and excitotoxicity.

Neurotransmitter modulation: It can influence the levels and function of various neurotransmitters like acetylcholine, glutamate, and GABA.

Uses of Cerebrolysin

Cerebrolysin is used to treat various neurological conditions, including:

1. Stroke:

Cerebrolysin has shown some promise in improving recovery after ischemic stroke, which occurs when a blood clot blocks an artery in the brain. Studies suggest that it may enhance neurological function, reduce brain damage, and promote recovery.

2. Dementia and Alzheimer's Disease:

Cerebrolysin is often used to treat cognitive decline in patients with Alzheimer's disease and other forms of dementia. Research shows that it might improve cognitive function, memory, and attention in these patients. However, the evidence is not consistent, and more research is needed to confirm its efficacy.

3. Traumatic Brain Injury:

Cerebrolysin is sometimes used to treat patients with traumatic brain injury to improve cognitive function and reduce neurological deficits. However, the evidence supporting its use in this condition is limited.

4. Other Neurological Conditions:

Cerebrolysin is also used in various other conditions, including:

Cognitive impairment in Parkinson's disease

Multiple sclerosis

Spinal cord injury

Peripheral neuropathy

Side Effects of Cerebrolysin

Like any medication, Cerebrolysin can cause side effects. These can range from mild to severe and may vary from person to person. Some common side effects include:

Allergic reactions: Some people may experience allergic reactions to Cerebrolysin, including rash, itching, hives, swelling, and difficulty breathing.

Nausea: This is a common side effect, especially when Cerebrolysin is administered intravenously.

Headache: Headaches can occur in some patients.

Dizziness: Some individuals may experience dizziness, particularly when standing up quickly after sitting or lying down.

Fatigue: Cerebrolysin can cause fatigue or tiredness.

Skin reactions: In some cases, skin reactions like redness, itching, or rash can occur at the injection site.

Safety of Cerebrolysin

The long-term safety of Cerebrolysin is unclear. While short-term use is generally considered safe for most patients, its long-term effects are not fully understood.

1. Risk of Infectious Diseases:

Because Cerebrolysin is derived from porcine brain tissue, there is a potential risk of transmitting infectious diseases. While rigorous screening and processing procedures are in place to minimize this risk, it remains a concern.

2. Drug Interactions:

Cerebrolysin may interact with certain medications, such as anticonvulsants and antidepressants. It's crucial to inform your doctor about all medications you are taking before starting Cerebrolysin therapy.

3. Pregnancy and Breastfeeding:

The safety of Cerebrolysin during pregnancy and breastfeeding is not established. It's important to consult with a healthcare professional to weigh the risks and benefits before using Cerebrolysin during these periods.

How to Use Cerebrolysin

Cerebrolysin is typically administered intravenously (IV) or intramuscularly (IM). The dosage and frequency of administration will depend on the individual's condition and response to treatment.

It's crucial to follow the doctor's instructions carefully and never exceed the recommended dose.

Effectiveness of Cerebrolysin

The evidence supporting Cerebrolysin's effectiveness in various conditions varies. While some studies show positive results, others show mixed or inconclusive findings.

Stroke:  The National Institute of Neurological Disorders and Stroke (NINDS) https://www.ninds.nih.gov/Disorders/All-Disorders/Cerebrolysin states that Cerebrolysin has shown some promise in improving recovery after ischemic stroke.

Alzheimer's Disease: The Alzheimer's Association https://www.alz.org/alzheimers-dementia/treatments notes that Cerebrolysin is often used to treat Alzheimer's disease, but more research is needed to confirm its efficacy.

Dementia: While some studies suggest that Cerebrolysin might improve cognitive function in dementia, more research is needed to confirm its effectiveness.

Alternatives to Cerebrolysin

Several alternative treatments are available for the conditions that Cerebrolysin is used to treat. These include:

Medications: There are various medications available to treat stroke, Alzheimer's disease, dementia, and other neurological conditions.

Cognitive therapy: This type of therapy can help improve cognitive function in patients with dementia and other cognitive impairments.

Lifestyle modifications: Making lifestyle changes like eating a healthy diet, exercising regularly, and managing stress can help reduce the risk and progression of many neurological conditions.

Frequently Asked Questions

1. Is Cerebrolysin available in the United States?

Cerebrolysin is not currently approved by the Food and Drug Administration (FDA) for use in the United States. However, it is available in many other countries.

2. How long does it take for Cerebrolysin to work?

The time it takes for Cerebrolysin to show its effects can vary depending on the individual and the condition being treated. It may take several weeks or months to see significant improvements.

3. What are the potential risks of using Cerebrolysin?

The potential risks of using Cerebrolysin include allergic reactions, nausea, headaches, dizziness, fatigue, and potential transmission of infectious diseases.

4. Can I stop taking Cerebrolysin suddenly?

It's important to discuss with your doctor before stopping Cerebrolysin therapy, as sudden discontinuation might lead to withdrawal symptoms or worsen your condition.

5. Is Cerebrolysin covered by insurance?

Insurance coverage for Cerebrolysin varies depending on the individual's plan. Check with your insurance provider to determine coverage.

6. Who should not use Cerebrolysin?

Individuals with a history of allergic reactions to porcine products or who are pregnant or breastfeeding should not use Cerebrolysin. It's essential to consult with a healthcare professional to determine if Cerebrolysin is appropriate for you.

Conclusion

Cerebrolysin is a controversial medication with potential benefits and risks. While some evidence supports its use in certain neurological conditions, further research is needed to clarify its efficacy and safety.

It's essential to discuss the potential benefits and risks with your healthcare provider before considering Cerebrolysin therapy. They can help you make an informed decision based on your individual needs and medical history.

[projectorthus]

I got hyperfixated on MSG once and so I know Way Too Much About It. When people try to use science to demonize it they say “glutamate causes excitotoxicity in the brain which damages the brain!” Yes glutamate causes excitotoxicity. But eating monosodium glutamate will NOT raise glutamate levels in your brain enough to cause that, if at all.

MSG is tasty as hell. If you feel like you’re sensitive to it, fine. Just don’t be a dick about it and pretend like its evil to everyone. It’s a seasoning. It naturally occurs in many fruits. And seaweed. It’s used in all sorts of fast food and chips, but somehow only Chinese restaurants get flack for using it. If you claim to be sensitive to MSG but you continue to eat doritos, pringles, KFC, etc, then you’re wrong.

Genuinely, I don’t know how else to get the word out, but I feel like if your home-cooked dinners don’t taste right, you're missing either paprika, sugar, butter, or chicken bouillon.

[heartheathblogs]

Understanding the Pathophysiology of Ischemic Stroke: A Detailed Insight

Understanding the pathophysiology of ischemic stroke involves a detailed examination of how this condition disrupts normal brain function. An ischemic stroke occurs when a blood clot or other blockage obstructs a cerebral artery, reducing blood flow to a specific area of the brain. This interruption in blood supply leads to a lack of oxygen and nutrients, causing brain cells to become deprived. As the affected neurons struggle to survive, they undergo a series of pathological changes.

Initially, the reduction in blood flow results in immediate cellular energy failure and the release of excitotoxic neurotransmitters, which further damages surrounding neurons. Inflammatory responses are triggered, leading to swelling and additional injury. The brain's inability to remove waste products due to impaired circulation exacerbates the damage.

As the stroke progresses, secondary injury mechanisms, including oxidative stress and apoptosis (programmed cell death), compound the damage. Understanding these processes is crucial for developing effective treatments, as targeting specific pathways involved in the ischemic cascade could potentially minimize brain damage and improve outcomes for stroke patients.

[avnnetwork]

Revolutionary Neuroprotective Medication Offers New Hope for Brain Health

Introduction

Brain health is a critical aspect of overall well-being, influencing everything from cognitive functions to emotional stability. As we age, the risk of neurodegenerative diseases such as Alzheimer's, Parkinson's, and multiple sclerosis increases, posing significant challenges for individuals and healthcare systems worldwide. In recent years, the development of neuroprotective medications has emerged as a revolutionary approach to preserving brain health and offering new hope for patients suffering from these debilitating conditions.

Understanding Neuroprotection

Neuroprotection refers to strategies and mechanisms that protect the nervous system from injury and degeneration. These strategies aim to preserve neuronal structure and function, prevent cell death, and promote recovery in the event of damage. Neuroprotective medications are designed to combat various pathological processes, including oxidative stress, inflammation, and excitotoxicity, which contribute to neuronal damage.

Key Mechanisms of Neuroprotection

Oxidative Stress Reduction: Oxidative stress results from an imbalance between free radicals and antioxidants in the body, leading to cell damage. Neuroprotective medications often include antioxidants to neutralize free radicals and reduce oxidative stress.

Anti-inflammatory Actions: Chronic inflammation is a common feature of neurodegenerative diseases. Neuroprotective drugs target inflammatory pathways to reduce inflammation and protect neurons from damage.

Excitotoxicity Prevention: Excitotoxicity occurs when excessive stimulation by neurotransmitters, particularly glutamate, leads to neuronal injury. Neuroprotective agents work to modulate neurotransmitter levels and prevent excitotoxic damage.

Mitochondrial Support: Mitochondria are crucial for energy production in cells. Neuroprotective medications aim to enhance mitochondrial function, ensuring neurons have the energy needed to maintain health and function.

Promotion of Neurogenesis: Some neuroprotective agents stimulate the growth and development of new neurons, a process known as neurogenesis, which can help repair damaged brain tissue.

The Evolution of Neuroprotective Medications

The journey to develop effective neuroprotective medications has been long and complex. Early efforts focused on understanding the fundamental mechanisms of neuronal damage and identifying potential targets for intervention. Advances in molecular biology, genetics, and pharmacology have significantly accelerated this process, leading to the discovery of several promising compounds.

Early Discoveries and Challenges

Initial neuroprotective strategies centered around the use of antioxidants and anti-inflammatory agents. While these approaches showed some promise in preclinical studies, translating these findings into effective treatments for humans proved challenging. One major hurdle was the complexity of the brain's biochemistry and the difficulty in delivering drugs across the blood-brain barrier (BBB). Visit https://rxeli.com/product/afobazole-fabomotizole-10mg-60-tablets/

Breakthroughs in Drug Delivery

Overcoming the BBB has been a significant focus of neuroprotective drug research. This selective barrier prevents many substances from entering the brain, making it difficult to deliver therapeutic agents effectively. Recent advancements in nanotechnology and molecular engineering have led to the development of novel delivery systems, such as nanoparticles and liposomes, capable of crossing the BBB and delivering drugs directly to target sites in the brain.

Innovative Therapeutic Targets

Researchers have also identified new therapeutic targets for neuroprotection. These include specific receptors, enzymes, and signaling pathways involved in neurodegenerative processes. By designing drugs that specifically interact with these targets, scientists can develop more effective and precise treatments for neurodegenerative diseases.

Promising Neuroprotective Medications

Several neuroprotective medications have shown significant promise in preclinical and clinical studies. These drugs target various aspects of neuronal damage and offer hope for treating a range of neurodegenerative conditions.

Antioxidant-Based Therapies

Antioxidant-based therapies aim to reduce oxidative stress and protect neurons from damage. Some compounds, such as resveratrol and coenzyme Q10, have demonstrated neuroprotective effects in animal models and small clinical trials. These agents work by neutralizing free radicals and enhancing the brain's antioxidant defenses.

Anti-inflammatory Agents

Inflammation plays a crucial role in the progression of neurodegenerative diseases. Anti-inflammatory agents, including certain nonsteroidal anti-inflammatory drugs (NSAIDs) and specialized compounds targeting inflammatory pathways, have shown potential in reducing neuroinflammation and slowing disease progression.

Neurotrophic Factors

Neurotrophic factors are proteins that support the growth, survival, and differentiation of neurons. Some neuroprotective medications are designed to mimic or enhance the activity of these factors, promoting neuronal health and function. For example, certain drugs aim to increase the levels of brain-derived neurotrophic factor (BDNF), a protein critical for neuronal survival and plasticity.

Mitochondrial Enhancers

Mitochondrial dysfunction is a hallmark of many neurodegenerative diseases. Medications that enhance mitochondrial function and energy production can help protect neurons from damage. These drugs often work by improving mitochondrial efficiency, reducing oxidative stress, and promoting cellular energy balance.

Synaptic Modulators

Synaptic dysfunction is a common feature of neurodegenerative diseases, leading to impaired communication between neurons. Synaptic modulators are drugs that aim to restore normal synaptic function and improve cognitive abilities. These medications often target neurotransmitter systems, such as the cholinergic and glutamatergic systems, to enhance synaptic plasticity and communication.

Case Studies and Clinical Trials

The development of neuroprotective medications involves rigorous testing in preclinical and clinical settings. Several drugs have advanced to clinical trials, offering valuable insights into their safety and efficacy.

Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta plaques and tau tangles in the brain. Several neuroprotective drugs targeting these pathological features are currently in clinical trials. For instance, certain compounds aim to prevent the aggregation of amyloid-beta and tau proteins, reducing their toxic effects on neurons. Early results from these trials have shown promise, with some drugs demonstrating the ability to slow cognitive decline in AD patients.

Parkinson's Disease

Parkinson's disease (PD) involves the progressive loss of dopaminergic neurons in the brain. Neuroprotective medications for PD focus on protecting these neurons and enhancing dopamine signaling. Some drugs aim to reduce oxidative stress and inflammation in the brain, while others target mitochondrial function to support neuronal health. Clinical trials have provided encouraging results, showing potential for these medications to slow disease progression and improve motor function in PD patients.

Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that damages the protective covering of nerves. Neuroprotective strategies for MS aim to reduce inflammation and promote repair of damaged neurons. Certain drugs target specific immune pathways to prevent neuronal damage, while others enhance neurogenesis to facilitate the repair of damaged tissue. Clinical studies have shown that these approaches can reduce the frequency and severity of MS relapses, improving the quality of life for patients.

Future Directions in Neuroprotective Research

The field of neuroprotective research is continually evolving, with new discoveries and technologies driving progress. Several exciting directions hold promise for the future of brain health.

Personalized Medicine

Personalized medicine involves tailoring treatments to individual patients based on their genetic, biochemical, and clinical profiles. Advances in genomics and biomarker research are enabling the development of personalized neuroprotective therapies. By identifying specific molecular targets and pathways involved in each patient's disease, researchers can design more effective and individualized treatments.

Combination Therapies

Combining multiple neuroprotective strategies may offer synergistic benefits for brain health. Researchers are exploring combination therapies that target different aspects of neuronal damage simultaneously. For example, a drug that reduces oxidative stress might be combined with one that enhances mitochondrial function, providing a comprehensive approach to neuroprotection.

Regenerative Medicine

Regenerative medicine aims to repair or replace damaged tissues and organs, including the brain. Stem cell therapies and tissue engineering techniques hold promise for regenerating damaged neurons and restoring brain function. While still in the experimental stages, these approaches could revolutionize the treatment of neurodegenerative diseases in the future.

Advanced Drug Delivery Systems

Innovations in drug delivery systems are improving the effectiveness of neuroprotective medications. Nanotechnology, for instance, enables the creation of nanoparticles that can cross the BBB and deliver drugs directly to target sites. Additionally, advances in gene therapy are allowing for the delivery of therapeutic genes to specific brain regions, offering a novel approach to neuroprotection.

Artificial Intelligence and Machine Learning

Artificial intelligence (AI) and machine learning are transforming the landscape of drug discovery and development. These technologies can analyze vast amounts of data to identify potential neuroprotective compounds and predict their efficacy. AI-driven approaches are accelerating the discovery of new drugs and optimizing existing treatments, ultimately improving outcomes for patients.

Conclusion

The development of neuroprotective medications represents a revolutionary advancement in the field of brain health. By targeting the underlying mechanisms of neuronal damage, these drugs offer new hope for patients suffering from neurodegenerative diseases. From antioxidant-based therapies to advanced drug delivery systems, the future of neuroprotection is bright and full of promise.

As research continues to uncover the complexities of the brain and neurodegenerative diseases, the potential for neuroprotective medications to improve quality of life and extend cognitive health is becoming increasingly clear. While challenges remain, the progress made thus far provides a solid foundation for future breakthroughs in brain health.

[the2amrevolution]

Part of the problem is that CFS/ME is unlikely to be just one pathology. Its a syndrome - a collection of symptoms. Thats part of why I have never been satisfied with that answer and so have tried to keep up with research into its pathology and comparing things I've found to my own symptoms. Following that research is what led to me reading about MTHFR mutations, which led me to taking methylfolate, which led to me discovering I likely have both a methylcobalamin deficiency and pyridoxal-5-phosphate deficiency that are the root of my CFS, POTS, worsening MCAS, hypersomina, and other progressive symptoms.

MTHFR mutations affect between 1 in 3 and 1 in 10 people, depending on race and nationality. They cause a deficiency in methylfolate which raises homocysteine levels and has a similar effect to a B12 or folate deficiency, but with normal B12 and folate levels.

Cobalamin metabolism disorders are more rare, but they are also very easily missed because total B12 blood tests are normal. The most common cobalamin metabolism disorder causes a deficiency of the usable forms of B12, leading to elevated methylmalonic acid and elevated homocysteine as would be seen in a B12 deficiency from diet or malabsorption. More rare disorders, or currently unknown and so undiagnosed disorders, can cause just a deficiency of methylcobalamin which will have nearly identical symptoms to a methylfolate deficiency.

One research team has hypothesized that an autoimmune disorder affecting the production of adenosylcobalamin may be behind multiple sclerosis. Impaired B12 metabolism leads to defective myelin, which the immune system tries to clear out. Something similar happens with methylcobalamin deficiency. Only genetic cobalamin metabolism disorders are recognized currently, but there could be autoimmune forms as well.

Similarly, some researchers think MTHFR mutations may be behind the trifecta of hEDS, POTS, and MCAS where patients often also fit CFS/ME and fibromyalgia criteria. Methylfolate deficiency can cause methylcobalamin deficiency, and methylcobalamin deficiency also leads to faulty myelin. Methylfolate and methylcobalamin deficiencies also cause problems with how DNA is read to make proteins, leading to faulty collagen, more damaged enzymes, and a variety of other metabolic problems.

The degree of impairment of the enzymes involved would impact the degree of severity of the damage done to the body. A mild deficiency over time would cause a slow, steady increase in platelet count, worsening allergies/MCAS reactions (homocysteine can trigger mast cells), and a wide variety of neurological symptoms as myelin degrades from lack of methylcobalamin and homocysteine causes excitotoxity.

While researching this, I found that there may also be millions of people with a functional pyridoxal phosphate deficiency who have no idea and no doctor is going to know to look for it. The people at risk are those who take B6 supplements and anyone who takes replacement thyroid hormones, both T4 and T3.

Most B6 supplements are a form of the vitamin called pyridoxine hydrochloride. This form can't be used by the body as is, it has to be converted into pyridoxal phosphate first. However, if taken at dosages that overwhelm the conversion to PLP, the pyridoxine itself can bind to PLP receptors on enzymes and block their function.

Free thyroid hormones also bind to PLP receptors, and they do it readily. A study in the 1950s found giving thyroid hormones to rats significantly blocked PLP enzyme function, especially in the liver. Ingested thyroid hormones are free when absorbed by the intestines and sent to the liver, and from there they can bind to carrier proteins which keep them from going places they aren't supposed to. In order to stop the thyroid hormones from interfering with the PLP enzymes, you need to significantly increase how much PLP is in the blood. How much more exactly is unknown, but is likely proportionate to the hormone dosage. Without supplementation or a diet quite high in natural B6 sources (not fortified sources), the body will start to use up the PLP it has stored up in the past. How fast someone depleates their PLP stores depends on how much B6 they get from their diet and thyroid hormone dosage. Functional PLP deficiency has the same symptoms as B6 deficiency, but bloodtests for the vitamin will be "normal." The demand for the vitamin is greater, so standard deficiency screenings aren't going to be useful.

PLP deficiency can also cause elevated homocysteine. Since enzymes in the intestines and liver are the most affected, people may have changes in gastric motility and in liver function tests. Over time, as the stores of PLP run low, people would develop signs of an overall B6 deficiency including neuropathy, dry and cracking skin, mood and sleep changes (PLP is necessary to make serotonin, dopamine, and melatonin), systemic inflammation and oxidative stress (PLP is needed to make the bodies most abundant antioxidant), and liver damage or disease.

Theres also a number of genetic conditions that can affect PLP levels, and, theoretically, there could be an autoimmune impact of PLP metabolism, so people who aren't taking thyroid hormones or pyridoxine can still have a PLP deficiency with normal total B6. PLP levels can be specifically tested and would show low in most of those cases.

The best news about both methylcobalamin and PLP deficiencies is that they are treatable without a prescription. Methylcobalamin lozenges or liquid for sublingual administration (to avoid the first pass effect which would make the supplement useless for the specific conditions that cause low methylcobalamin) and pyridoxal-5-phosphate/P5P/PLP are both available for a fairly low price online. Both are water soluble with limited uptake to storage and no toxicity, so whatever isn't either used or stored will be excreted in urine.

I have had CFS since fall of 2015. I was diagnosed with Hashimoto's and began taking thyroid hormones spring of that year. The onset and progression of all of my symptoms match having either a methylfolate or methylcobalamin deficiency combined with a PLP deficiency.

Taking methylfolate when you dont have a deficiency will increase demand for methylcobalamin, and if you can't meet that demand you will get sicker. Thats what happened to me, even though I was taking a normal B12 supplement and had high serum B12 - thus indicating the methylcobalamin deficiency. I got a methylmalonic acid blood test which indicated no deficiency of adenosylcobalamin, which eliminated the more common cobalamin metabolism disorders. I'd rather be extra rare than have a trio of deficiencies though.

If you take methylcobalamin without a deficiency, nothing changes and you pee it out. If you take it and you have a methylfolate deficiency, nothing changes and you pee it out. If you take pyridoxal phosphate without a deficiency, nothing changes and you pee it out.

These supplements do not interfere with any medications. Thyroid hormones can impair PLP enzymes, but PLP has no effect on thyroid hormone receptors.

This means that methylcobalamin and PLP are easily accessible and safe supplements that people with CFS/ME, fibromyalgia, and/or hEDS trifecta can try even if they don't have access to a helpful doctor.

The remaining question is how long they take to have effect. I can tell you that the PLP helped me in a matter of days. Better energy, better executive function, and some improvement to sleep. The methylcobalamin will take longer to have impact as the major effect of the deficiency is damage to the nervous system.

My neurological symptoms primarily come from the lumbar region of my spinal cord and the reticular formation of my brainstem. I dont know of any way to predict what parts of the nervous system get affected most, but by listing out all of my symptoms and learning the functions of different parts, I was able to trace all of my neurological symptoms to those two places.

Based on other types of B12 deficiency and other adult-onset cobalamin metabolism disorders, treatment has the potential to lead to full healing of damage done in the course of the deficiency. Lasting damage seemed to mostly be in cases where patients presented with strokes, embolism, etc. which caused additional damage. Other patients have full recovery as long as they continue to have the form of B12 they need.

I've so far only been taking the methylcobalamin for less than a week. Thats not enough time to recover from 8 years of damage, unfortunately. Right now I just have to wait and not push my neurological limitations just because I have more energy and focus. I have some very objective symptoms that are what I'll be monitoring most, since others like chronic widespread pain are more easily influenced by other factors. Im hoping that I will be able to point to definite improvement of at least a symptom after a month, but it could take longer. There's honestly no way to know.

Now, disclaimer, I am not a doctor or any other licensed medical professional. I'm a disabled person with the resources to experiment on myself and the ability and education necessary to understand the science enough to connect the dots and weigh the risks. I weighed the risk of taking methylfolate, but I turned out to be an outlier with a 1 in 100 million condition rather than the 1 in 3 for my demographic (granted the 1 in 100 million may be wrong, but thats the approximate current diagnosis rate). However, since what I found indicates zero risk for trialing methylcobalamin and/or PLP, I feel comfortable sharing what I've learned and what I am doing. Its always a good idea to talk to a pharmacist about possible interactions and to talk to a doctor about any other conditions you may have, and taking any supplement is always at your own risk.

I also understand the desperation of people chronic pain, fibromyalgia, and/or CFS/ME for anything that may help their condition, and it is hard for me to keep information to myself while I wait to see how things go, when the information has the potential to start helping someone who may not be able to make it until I have everything in a clear presentation format and my personal results.

As I continue my own treatment trial, I will be reaching out to various doctors and researchers about this and sharing more about my history, research, and how things are going. I will also be working on having cited, edited, clear, and easy to distribute information rather than... this or "look into trying these supplements and just trust me" which sounds about as useful and trustworthy as "try yoga."

even if you did the barest minimum research, the Wikipedia page for chronic fatigue syndrome is so sad. it’s like “this is what we diagnose people with when we can’t find anything else wrong with them. but it’s definitely something physical because there are visible neurological changes seen in neuroimaging and weirdness with the immune system. full recovery rates are less than 5%. the most common treatment is CBT which ignores the fact it is a physical illness and tells sick people they’ll get better if they just stop thinking about being sick.”

[jhavelikes]

Tropoflavin, also known as 7,8-dihydroxyflavone, is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves.[2][3][4] It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB) (Kd ≈ 320 nM), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF).[5][6][7] Tropoflavin is both orally bioavailable and able to penetrate the blood–brain barrier.[8][9] A prodrug of tropoflavin with greatly improved potency and pharmacokinetics, R13 (and, formerly, R7), is under development for the treatment of Alzheimer's disease.[10][11] Tropoflavin has demonstrated therapeutic efficacy in animal models of a variety of central nervous system disorders,[7] including depression,[8] Alzheimer's disease,[12][13][14] cognitive deficits in schizophrenia,[15] Parkinson's disease,[5] Huntington's disease,[16] amyotrophic lateral sclerosis,[17] traumatic brain injury,[18] cerebral ischemia,[19][20] fragile X syndrome,[21] and Rett syndrome.[22] Tropoflavin also shows efficacy in animal models of age-associated cognitive impairment[23] and enhances memory consolidation and emotional learning in healthy rodents.[24][25] In addition, tropoflavin possesses powerful antioxidant activity independent of its actions on the TrkB receptor,[26] and protects against glutamate-induced excitotoxicity,[27] 6-hydroxydopamine-induced dopaminergic neurotoxicity,[28] and oxidative stress-induced genotoxicity.[29] It was also found to block methamphetamine-induced dopaminergic neurotoxicity, an effect which, in contrast to the preceding, was found to be TrkB-dependent.

Tropoflavin - Wikipedia