My understanding was that strokes caused brain cell death, and that there was no coming back from that, but my neurologists would speak of 'bruised' brain cells, and that after weeks or months or even years you can see recovered function. UCLA's work here is targeting this disconnection and the lost rhythm in the surviving, distant networks. However there is, as yet, NO concievable intervention that could recover function from cell death at that center of the infarct.
My understanding is that while brain cell death (outside of the hippocampus, at least) cannot regenerate, the connections and networks can.
But neurons regenerating connections between each other is, afaik, been pretty mainstream for awhile. The brain can't generate new cells, but it can rewire the connections between them, is what I understand. From reading the article, it seems to only claim rewiring connections, not regenerating cells.
There are a ton of upcoming drugs that help stimulating rewiring, for instance:
I'm not sure why this being disagreed to without any response. There are studies related to this out on PubMed. The effects do not seem huge, but they do seem to be significantly better than placebo. And at least those studies are in humans as opposed to the main article of this post that is only in mice.
Note that none of these address neural regeneration (after concussions, as claimed by oneshtein) because I'll leave that for the supporters to demonstrate.
I won't talk about Lion's Mane specifically, but there is a ton of science about things that induce neurotrophic growth factor, which some claim Lion's Mane to do, and research in concussions, depression, and Alzheimer's disease/dementia. These drugs are for the most part pretty new and quite expensive. Interestingly a lot of them are NMDA agonists, which... a drug you have heard of that works on that receptor is Ketamine, which has become popular for depression - leading a divergence of theories for why it works for depression - the most common being there is some therapeutic value in the dissociative state/"hallucinations", while a minority have claimed that it's actually the NMDA agonist property that is triggering neurotropic growth factor to repair brain damage, and the disassociation is a side effect.
You say all of these things and claim "there is a ton of science", but I ask for scholarly links to learn more. I don't trust anyone's word at face value on empirical topics, and I also don't know where to begin looking. "There are studies related to this out on PubMed." Show me! Phrases like this annoy me greatly.
Yeah, psychology studies are weak like that. Here is one with links to many other in vivo and in vitro studies, including some dealing with NGF and stroke (mice and rats). Quality varies.
I imagine because it reads like one of those "Big Medicine won't let you have access to stuff that works!" conspiracy theories, and also that it won't actually foster new brain cell growth.
It's ashame stuff gets strawmanned like that. It's not like there's a secret cabal restricting access. It's just there are many things with limited research because there's no money in it. Both the meds in the article and the lions mane studies show promising results in rats/mice. Anyone can guess which one will get more money because one is patentable and the other is not.
A lot/most of the neural regeneration drugs are still very much on patent, and very very very expensive, and a lot of insurance doesn't cover them.
While there may be some conspiracy stuff there, "big medicine" saying you need to pay $20k/yr out of pocket for something will definitely lead people to find alternatives.
The original paper did not say that a huge percentage of their brain was missing [1], that was the journalist's flourish based on their own misunderstanding.
Tissue can be compressed, stretched, reorganized, or displaced especially to compensate for a congenital condition - the patient's brain had a lifetime to adapt to hydrocephalus, which pushed on the other brain tissue. The gray cortical shell is clearly visible in those images and their volume on a scan is not representative of neuron count or synaptic capacity.
There are far more dramatic cases of brain damage and neuroplasticity that reorganizes major functions, but there are a lot of caveats.
My understanding is that brain is composed of way more neurons than required, for resiliency. So if it gets a "bruise" in some part, when even a large portion of the cells are dead -- it can still function at 100%. Like a programmer without a finger. The problem is visible only when all the cells in some part are dead.
That's why crows, with their low brain mass are pretty clever (and why all arguments equating brain size and smartness are wrong).
Crows (and certain other bird species) have a peculiar forebrain (different in structure but similar in function/evolution to the neocortex in mammals) with neuron counts rivalling primates. So the nr of neurons still matters, but likely not across the entire brain.
Yep. And my point is that too many people seem to judge intellect by brain size or mass. Something like "Neanderthals must've been smarter than Sapiens, because their brains were larger". Or "chimpanzees are smarter than gorillas because gorillas have very small brains", which is all true, except for the word "because" (gorillas are leaf-eaters, so they did not have evolutionary pressure to be smarter, no need in more complex hierarchies, and maybe less proteins for the brain).
Obviously an M1 chip is “smarter” in terms of raw accuracy for eg matrix computations than any equivalent wetware despite being much? smaller. Performance per watt at least at that task has to be an ocean of a difference.
my understanding is that extream migrators actualy consume (use as energy) parts of there own brains durring there epic flights, and other species do something similar in the winter and regrow parts of there brains every spring.
It is true that they can shrink some organs to reduce weight and store extra fat, but the brain is not one of them. Would be pretty bad, because brain cells can't regrow like e.g. a liver can.
There've been some interesting new developments in cell therapies over the last few years. Bemdaneprocel from BlueRock Therapeutics is now into Phase 3 trials for Parkinson's, for example. The essential idea is to implant some dopaminergic neuron precursors to grow new cells in place of cell death. Still a long way from the kind of general stroke treatment you're describing, but regenerative neuroscience is looking pretty promising.
One wonders if someday we might be able to resurrect the neural network from dead cells by somehow reviving the connections between neurons. I imagine that the connections stay, but become dormant when the neuron dies.
Strokes will never be preventable. You can mitigate them but a stroke isn't really a disease. It's a symptom.
An ischemic stroke (i.e. stroke due to a clot) caused by vascular or cardiac issues can be mitigated. A cryptogenic stroke however is idiopathic and therefore has no understood cause. These types of strokes make up 30-40% of all strokes. Unless we figure out their cause, there's no way to really prevent them.
But then there's also hemorrhagic strokes which are an entirely separate category that has causes and mitigations more or less diametrically opposed to those for ischemic strokes.
And of course those are just your broad painted categories and they are generally looked at as the start of a medical emergency but strokes happen all the time as a consequence of other medical emergencies.
Even if you could perfectly prevent strokes in generally healthy populations, those same people may still end up suffering from a stroke during a surgery or during/after a major accident or injury. No amount of preventative medication can prevent someone suffering a stroke caused by a brain bleed after a car accident. Likewise for someone with a crush injury, internal bleeding, or broken bones that end up throwing a clot which makes it into the brain.
So any advancement in halting and reversing damage from a stroke will be a massive boon for emergency medicine until the end of time. Unless of course we somehow find a way to cure/render humans immune to blunt force trauma or lacerations.
Sure you can. Just not with any technology on the horizon. But there is conceivable technology (e.g. medical nanotechnology) that could prevent strokes or stop them as they are happening.
Like detecting constriction or loss of integrity of blood vessels, and doing the corresponding intervention.
The saddest thing here is not that it requires some future nanotechnology, but is achievable at the present scientific level, yet too expensive to develop, and wouldn't see FDA permission in a decade or two anyway.
it is more like that the brain learns to use other regions or neurons to do the tasks of the dead brain cells. The brain cells that are dead due to ischemia are dead and will usually be collected by microglia and after some time there are defects in the brain where the ischemia was.
If you've read Ted Chiang's "Understand," you'll understand why this headline made my eyes pop out. For those who haven't, it's in the "Stories of Your Life and Others" collection, which includes the short story that the film Arrival was based on.
I'm a big fan of Ted Chiang's "Understand" short story, but I think your way over hyping the study there: more neuron growth does not even generally translate to higher intelligence and can often introduce a variety of degenerative effects because pathways are not being grown a an organized systematic way through natural process of experience adaptation.
Thanks for the hint. I'd always thought the movie was inspired by Vonnegut's Slaughterhouse 5. The premise was the same, and even the aliens looked somewhat similar. Vonnegut jokingly described them as an upside down toilet brush.
> This type of neuron helps generate a brain rhythm, termed a gamma oscillation, which links neurons together so that they form coordinated networks to produce a behavior, such as movement. Stroke causes the brain to lose gamma oscillations. Successful physical rehabilitation in both laboratory mice and humans brought gamma oscillations back into the brain and, in the mouse model, repaired the lost connections of parvalbumin neurons.
>Carmichael and the team then identified two candidate drugs that might produce gamma oscillations after stroke. These drugs specifically work to excite parvalbumin neurons.
Asking while being total layperson here - can we generate those gamma oscillations by an [may be implanted] electronic device?
Edit: and google search to help, judging by the dates seems to be a pretty fresh field :
"... by pairing robotic rehabilitation with a clinical-like noninvasive 40 Hz transcranial Alternating Current Stimulation, we achieved similar motor improvements mediated by the effective restoring of movement-related gamma band power, improvement of PV-IN maladaptive network dynamics, and increased PV-IN connections in premotor cortex. "
It also sounds like getting an exoskeleton for such patients can be helpful not only to perform immediate tasks, it also can be a part of the restoring process.
"DDL-920 is a potent, selective and brain permeable negative allosteric modulator (NAM) of the γ-aminobutyric acid type A receptors (GABARs), inhibits parvalbumin (PV) expressing interneurons (PV+INs) and consequently enhances γ-oscillations both in vitro and in vivo."
My understanding was that psychedelics have proven to be effective at opening up a “critical period” where a brain can rewire itself like when in childhood. Wonder if this is related.
> “The goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation,” said Dr. S. Thomas Carmichael, the study’s lead author and professor and chair of UCLA Neurology. “Rehabilitation after stroke is limited in its actual effects because most patients cannot sustain the rehab intensity needed for stroke recovery.
Sounds truly amazing, I have known two people who had severe strokes - one's PT was contingent on triaging resources to whoever was likely to recover more, another simply hated PT and speech therapy and often refused to participate or do the exercises. Even if it didn't help recovery a medicine like this would have reduced the stress of everyone involved.
Many different techniques for different types of stroke:
We can block certain arteries mechanically by inserting a tool, inject photosensitive agent then cause a targeted clot with a laser, inject clotting agent, choke, inject blood vessel dissolving agent and re-inject its own blood.
I understand why we research this but I just could not do it.
One of our family friends just could not continue draining monkeys of blood for biochemistry research. I have been to his lab. The monkeys would panic whenever their cages were touched.
I can one needs a level of sociopathy or psychopath to continue this kind of research.
As you write, we all have our own balances. I'd suggest there are ethical reasons against those.
As a society we have investigation review boards, laws, and other conventions.
There is a sizable set of people that like to outsource (want it done but not to do it) which seems dishonest, like the town butcher in Buddhism bring a bad karma sink.
In the particular non-hypothetical case I mentioned, the lab monkeys were a little too close to human babies in their behavior and appearance. That did not help at all.
Those who do not want partake in specific class of animal testing should also recuse themselves off the fruits of that class of experiments.
I think savvy universities want PIs who are savvy enough to realize that the point of these is to boost measurable visibility like citation count and h-index, so the headline of a news release boosting the article doesn't matter. They can always blame a copy editor for the headlines. It could read "world peace solved with moon juice." The provost would only care if it generated negative feedback. So it's the PR department's job to juice it as much as possible without getting blowback.
It really depends on how much the company wants to invest. If it really worked, then it would be relatively straightforward for them to put together a Phase II. Not cheap, but relatively straightforward. Or at least it would have been when we had a functioning FDA
Also, the other definition in question is what the UCLA PR person means by "repairing brain damage". As far as I can tell from the paper - the "drug" part was using some neurotransmitter blockers on brain cells on a Petri dish to see if they could change gene expression or oscillatory firing patterns matching recordings in mice undergoing "physical therapy". They did not actually test to see if the stuff grew new brain cells or dendritic connections.
Mice are used only partly because they share a considerable amount of DNA with us. But they're mostly used because they're cheap. Both in financial and ethical costs.
They live for about two years, and breed in about three months. They are disposable. Over 100 million are killed each year in various labs across the country.
And for all of this, only about 5% of medicine that show positive animal results make it to market in some fashion. So basically, the best thing we can say about a mouse-tested drug is that "this most likely won't make things worse". But that's like a low bar.
I think there's some kind of fallacy where you can look at five drugs, all of which came from a pool of 100 promising candidates, then look at the next 100 candidates and say for each one individually that it is not worth celebrating. I call it the, "rounding to zero" fallacy.
In reality, if you have 100 5% chances of a cure for a previously incurable illness, you can celebrate each chance a lot.
> In reality, if you have 100 5% chances of a cure for a previously incurable illness, you can celebrate each chance a lot.
These numbers are obviously entirely made up, but its worth noting that 100 5% chances of a cure, means you have at least 1 cure with (1-(.95)^100) = 99.4% probability.
If you are curing an incurable disease with 99.4% probability, celebrating a lot would be an understatement.
> And for all of this, only about 5% of medicine that show positive animal results make it to market in some fashion. A mildly positive result is a neccesary but not sufficient condition to make a marketable drug.
I'm surprised its that high tbh. And i suspect it would be a similar low number if we tested on humans instead of animals.
And yes, being able to test early stage ideas cheaply is critical to innovating. We use mice in biology for the same reason we use computer simulations in other fields.
Anyways, if we took your numbers of 5% chance at face value, that means there is a 1 in 20 chance of this press release turning into a real drug that saves real people's lives. Personally i dont think the chance is actually that high, but if it was that would only further my point that this is a milestone worth celebrating.
Hi, sorry, this is so disingenuous of a statement I cannot pass by it without commenting. My bona fides are 10y of lab work, specifically in bioenergetics. I can tell you that 5% is a dramatic UNDERESTIMATION on the value of animal models for medicine at large.
This is ignoring at least these benefits: surgery, development, genetic studies, grafts, anesthesia, and many MANY more. Some non-drug related, some drug adjacent, and they definitely have downstream benefits to humans.
I really don't like when bioscience articles land here in HN because they are always commented on with:"in mice", as if to say nothing we see from mouse work works. Well, not everything is software and this kind of work takes years, if not decades. It is real science unfortunately which means that most of it doesn't work! Science, and bioscience specifically, are not efficient systems. In general, the things you do are hard and probably won't work. That doesn't mean you give up.
Animal models are not great, but they are the best progression we can do right now from cell models. And as for being disposable, there are controls on how animals are used in labs in the US: every institution that has animal experimentation has an IACUC (institutional animal care and use committee) that every research proposal must go through, and they do not a rubber stamp your proposal. They want to know why you can't use cell models, and why you can't do it with less or even no animals.
It would be nice if people were a bit more even handed when these types of articles come by. I think HN can do better.
An adage from the lab: "If what we did always worked it would be business, not science."
If you don't sleep 8+ hours a day every single day, exercise regularly, live in a place with clean air, eat clean food, don't drink alcohol, etc. you're losing your time, no amount of supplement will make up for our modern way of life, you're going to optimise the 0.1% while missing the 99.9% that matters
That is true, but keep in mind that routine is very difficult to do for someone that makes their living running the rat race, with stress, no time, responsibilities, worry, untreated health problems, etc. If you have the money, job security, then you'll have peace of mind. That will then allow one to live that kind of optimized lifestyle.
There's (minimal) research on psilocybin doing just that. One of the tragedies of prohibition is that we just weren't able to study these psychedelic compounds easily for 50+ years.
Have any sources? I’d love to read what you are thinking about.
I haven’t used psilocybin in a clinical setting but have gone through an alternative psychedelic-assisted therapy process. Very interesting results and many positives.
There's not a lot, unfortunately. This paper is a literature review and the claims are weak, but there's something there that should be investigated further: https://pmc.ncbi.nlm.nih.gov/articles/PMC12392120/
Paul Stamets has evangelized psilocybin + lions mane + niacin for years in a microdosing format, but again, the research is lacking largely due to prohibition.
For sure, and lions mane is one of the three things Paul Stamets has been talking about for years to take in combination with niacin and psilocybin (microdose) to support neurogenesis. Low doses of psilocybin have only very mild perceptual changes, much less than smoking weed or drinking alcohol (for me). But again, there's not much science on it which will hopefully change.
I've read online that "Bacopa Monnieri" is a particularly strong and researched herbal supplement for cognitive maintenance, enhancement and neuroprotection, with the potential of supporting neurogenesis.
I've not tried that stuff since money is hard to come by these days. There have been a few human studies.
I’ve been researching potential solutions to stimulate neurogenesis, specifically looking for a combined approach that maximizes the beneficial effects of several powerful herbs while prioritizing safety and remaining affordable to the sub-middle class.
After some research and consultation with AI tools (obviously), I’ve narrowed down a promising blend of ingredients: Bacopa, Curcumin (with piperine – black pepper extract – to improve absorption), Lion’s Mane, Gotu Kola, NGF (delivered via eye drops or another method), Hericium Erinaceus, Marine Collagen, and Dimethylaminoethanol Bitartrate (DMAE).
The investigation has made it clear that truly effective neurogenesis isn’t just about boosting NGF levels. It requires a holistic strategy – carefully balancing metabolic pathways, antioxidant defenses, gut health, and inflammation modulation. Creating a supportive environment for neuronal survival, growth, and communication is key, and that includes addressing factors like stress management.
Perhaps one of the Bio-themed Tech bros on this forum might consider taking on this type of research endeavor. Or maybe there's an Eddie Morra-themed Tech bro that might have more "Limitless" how-to advice on the matter because the above to-do list is definitely, above my paygrade :)
Alpha-GPC and Uridine Monophosphate appear to have some effect, though minor. Also not exactly neurogenesis, but adjacent stuff. Evidence is complicated, there seems to be a signal but it's a weak effect.
It’s not as bad an analogy as you make it sound. It is more like “fire is what makes our factories run, and oil fuels fire. So let’s douse our factories in gasoline to speed things up.”
Nicotine is the only psychoactive substance proven to increase intellectual function. Rote neurogenisis does not - much in the same way height isn’t a proxy for IQ. Stimulants like Adderall, Caffiene, etc are Dunning-Kruger by proxy.
Maybe a better term is “stimulant-induced metacognitive miscalibration”. An induced a state of overconfidence similar to Dunning-Kruger - even thought the underlying mechanism is different.
You perceive the idea as great not because you suddenly understand it better or know more. You think the idea is great because of the dopamine flooding your brain. And much like Dunning-Kruger, even thought you might think you did better, real world results don’t match your expectations.
My understanding was that strokes caused brain cell death, and that there was no coming back from that, but my neurologists would speak of 'bruised' brain cells, and that after weeks or months or even years you can see recovered function. UCLA's work here is targeting this disconnection and the lost rhythm in the surviving, distant networks. However there is, as yet, NO concievable intervention that could recover function from cell death at that center of the infarct.
This talks about connections.
My understanding is that while brain cell death (outside of the hippocampus, at least) cannot regenerate, the connections and networks can.
But neurons regenerating connections between each other is, afaik, been pretty mainstream for awhile. The brain can't generate new cells, but it can rewire the connections between them, is what I understand. From reading the article, it seems to only claim rewiring connections, not regenerating cells.
There are a ton of upcoming drugs that help stimulating rewiring, for instance:
https://www.nia.nih.gov/news/new-drug-candidate-targeting-sy...
https://pmc.ncbi.nlm.nih.gov/articles/PMC8190578/
https://www.medicalnewstoday.com/articles/324410
etc.
There is lots of neural regeneration in the brain at the cellular level. The science on this is changing quickly.
But even though there are new brain cells growing, that does not mean you can reform lost structure.
Lion’s mane mushroom and extracts are used by boxers to repair their brains. But it cannot be patented.
I'm not sure why this being disagreed to without any response. There are studies related to this out on PubMed. The effects do not seem huge, but they do seem to be significantly better than placebo. And at least those studies are in humans as opposed to the main article of this post that is only in mice.
Please post specific articles for others to critique. I find poor quality studies. Low sample size, self-reported questionnaires, low effect sizes.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10675414/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12018234/
https://pubmed.ncbi.nlm.nih.gov/20834180/ I smell P-hacking.
Note that none of these address neural regeneration (after concussions, as claimed by oneshtein) because I'll leave that for the supporters to demonstrate.
I won't talk about Lion's Mane specifically, but there is a ton of science about things that induce neurotrophic growth factor, which some claim Lion's Mane to do, and research in concussions, depression, and Alzheimer's disease/dementia. These drugs are for the most part pretty new and quite expensive. Interestingly a lot of them are NMDA agonists, which... a drug you have heard of that works on that receptor is Ketamine, which has become popular for depression - leading a divergence of theories for why it works for depression - the most common being there is some therapeutic value in the dissociative state/"hallucinations", while a minority have claimed that it's actually the NMDA agonist property that is triggering neurotropic growth factor to repair brain damage, and the disassociation is a side effect.
You say all of these things and claim "there is a ton of science", but I ask for scholarly links to learn more. I don't trust anyone's word at face value on empirical topics, and I also don't know where to begin looking. "There are studies related to this out on PubMed." Show me! Phrases like this annoy me greatly.
You posted links earlier, which suffices.
I posted them in the GP comment
Yeah, psychology studies are weak like that. Here is one with links to many other in vivo and in vitro studies, including some dealing with NGF and stroke (mice and rats). Quality varies.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5987239/#B18
Thank you for sharing.
I imagine because it reads like one of those "Big Medicine won't let you have access to stuff that works!" conspiracy theories, and also that it won't actually foster new brain cell growth.
It's ashame stuff gets strawmanned like that. It's not like there's a secret cabal restricting access. It's just there are many things with limited research because there's no money in it. Both the meds in the article and the lions mane studies show promising results in rats/mice. Anyone can guess which one will get more money because one is patentable and the other is not.
A lot/most of the neural regeneration drugs are still very much on patent, and very very very expensive, and a lot of insurance doesn't cover them.
While there may be some conspiracy stuff there, "big medicine" saying you need to pay $20k/yr out of pocket for something will definitely lead people to find alternatives.
There are people who are missing huge percentages of their brain from injury or other issues and lead a seemingly normal life.
https://www.cbc.ca/radio/asithappens/as-it-happens-thursday-...
The original paper did not say that a huge percentage of their brain was missing [1], that was the journalist's flourish based on their own misunderstanding.
Tissue can be compressed, stretched, reorganized, or displaced especially to compensate for a congenital condition - the patient's brain had a lifetime to adapt to hydrocephalus, which pushed on the other brain tissue. The gray cortical shell is clearly visible in those images and their volume on a scan is not representative of neuron count or synaptic capacity.
There are far more dramatic cases of brain damage and neuroplasticity that reorganizes major functions, but there are a lot of caveats.
[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
Was expecting an article about
https://en.wikipedia.org/wiki/Hemispherectomy
It's wild to me that this can have effectively no impact on a person's cognitive ability.
My understanding is that brain is composed of way more neurons than required, for resiliency. So if it gets a "bruise" in some part, when even a large portion of the cells are dead -- it can still function at 100%. Like a programmer without a finger. The problem is visible only when all the cells in some part are dead.
That's why crows, with their low brain mass are pretty clever (and why all arguments equating brain size and smartness are wrong).
Just my layman understanding.
Crows (and certain other bird species) have a peculiar forebrain (different in structure but similar in function/evolution to the neocortex in mammals) with neuron counts rivalling primates. So the nr of neurons still matters, but likely not across the entire brain.
Yep. And my point is that too many people seem to judge intellect by brain size or mass. Something like "Neanderthals must've been smarter than Sapiens, because their brains were larger". Or "chimpanzees are smarter than gorillas because gorillas have very small brains", which is all true, except for the word "because" (gorillas are leaf-eaters, so they did not have evolutionary pressure to be smarter, no need in more complex hierarchies, and maybe less proteins for the brain).
Obviously an M1 chip is “smarter” in terms of raw accuracy for eg matrix computations than any equivalent wetware despite being much? smaller. Performance per watt at least at that task has to be an ocean of a difference.
my understanding is that extream migrators actualy consume (use as energy) parts of there own brains durring there epic flights, and other species do something similar in the winter and regrow parts of there brains every spring.
It is true that they can shrink some organs to reduce weight and store extra fat, but the brain is not one of them. Would be pretty bad, because brain cells can't regrow like e.g. a liver can.
There've been some interesting new developments in cell therapies over the last few years. Bemdaneprocel from BlueRock Therapeutics is now into Phase 3 trials for Parkinson's, for example. The essential idea is to implant some dopaminergic neuron precursors to grow new cells in place of cell death. Still a long way from the kind of general stroke treatment you're describing, but regenerative neuroscience is looking pretty promising.
---
[1] https://www.bluerocktx.com/bluerock-therapeutics-announces-p...
One wonders if someday we might be able to resurrect the neural network from dead cells by somehow reviving the connections between neurons. I imagine that the connections stay, but become dormant when the neuron dies.
There is nothing to resurrect. They get digested by the microglia.
Ah, I didn't know that existed. TIL
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Perhaps, but I think that by the time we're that far advanced, strokes will be entirely preventable.
Strokes will never be preventable. You can mitigate them but a stroke isn't really a disease. It's a symptom.
An ischemic stroke (i.e. stroke due to a clot) caused by vascular or cardiac issues can be mitigated. A cryptogenic stroke however is idiopathic and therefore has no understood cause. These types of strokes make up 30-40% of all strokes. Unless we figure out their cause, there's no way to really prevent them.
But then there's also hemorrhagic strokes which are an entirely separate category that has causes and mitigations more or less diametrically opposed to those for ischemic strokes.
And of course those are just your broad painted categories and they are generally looked at as the start of a medical emergency but strokes happen all the time as a consequence of other medical emergencies.
Even if you could perfectly prevent strokes in generally healthy populations, those same people may still end up suffering from a stroke during a surgery or during/after a major accident or injury. No amount of preventative medication can prevent someone suffering a stroke caused by a brain bleed after a car accident. Likewise for someone with a crush injury, internal bleeding, or broken bones that end up throwing a clot which makes it into the brain.
So any advancement in halting and reversing damage from a stroke will be a massive boon for emergency medicine until the end of time. Unless of course we somehow find a way to cure/render humans immune to blunt force trauma or lacerations.
Sure you can. Just not with any technology on the horizon. But there is conceivable technology (e.g. medical nanotechnology) that could prevent strokes or stop them as they are happening.
Like what?
Like detecting constriction or loss of integrity of blood vessels, and doing the corresponding intervention.
The saddest thing here is not that it requires some future nanotechnology, but is achievable at the present scientific level, yet too expensive to develop, and wouldn't see FDA permission in a decade or two anyway.
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it is more like that the brain learns to use other regions or neurons to do the tasks of the dead brain cells. The brain cells that are dead due to ischemia are dead and will usually be collected by microglia and after some time there are defects in the brain where the ischemia was.
If you've read Ted Chiang's "Understand," you'll understand why this headline made my eyes pop out. For those who haven't, it's in the "Stories of Your Life and Others" collection, which includes the short story that the film Arrival was based on.
I'm a big fan of Ted Chiang's "Understand" short story, but I think your way over hyping the study there: more neuron growth does not even generally translate to higher intelligence and can often introduce a variety of degenerative effects because pathways are not being grown a an organized systematic way through natural process of experience adaptation.
I just read this a few months ago and it was my first thought as well! Like Flowers for Algernon taken to its extremes.
Thanks for the hint. I'd always thought the movie was inspired by Vonnegut's Slaughterhouse 5. The premise was the same, and even the aliens looked somewhat similar. Vonnegut jokingly described them as an upside down toilet brush.
[flagged]
> This type of neuron helps generate a brain rhythm, termed a gamma oscillation, which links neurons together so that they form coordinated networks to produce a behavior, such as movement. Stroke causes the brain to lose gamma oscillations. Successful physical rehabilitation in both laboratory mice and humans brought gamma oscillations back into the brain and, in the mouse model, repaired the lost connections of parvalbumin neurons.
>Carmichael and the team then identified two candidate drugs that might produce gamma oscillations after stroke. These drugs specifically work to excite parvalbumin neurons.
Asking while being total layperson here - can we generate those gamma oscillations by an [may be implanted] electronic device?
Edit: and google search to help, judging by the dates seems to be a pretty fresh field :
https://journals.plos.org/plosbiology/article?id=10.1371/jou...
"... by pairing robotic rehabilitation with a clinical-like noninvasive 40 Hz transcranial Alternating Current Stimulation, we achieved similar motor improvements mediated by the effective restoring of movement-related gamma band power, improvement of PV-IN maladaptive network dynamics, and increased PV-IN connections in premotor cortex. "
It also sounds like getting an exoskeleton for such patients can be helpful not only to perform immediate tasks, it also can be a part of the restoring process.
It is this compound https://pubmed.ncbi.nlm.nih.gov/39106304/
DDL-920, which apparently looks like this: https://www.probechem.com/userfiles/product/PC-22875.gif
"DDL-920 is a potent, selective and brain permeable negative allosteric modulator (NAM) of the γ-aminobutyric acid type A receptors (GABARs), inhibits parvalbumin (PV) expressing interneurons (PV+INs) and consequently enhances γ-oscillations both in vitro and in vivo."
https://www.probechem.com/products_DDL-920.html
So my question does it work with Alzheimer's.?
My understanding was that psychedelics have proven to be effective at opening up a “critical period” where a brain can rewire itself like when in childhood. Wonder if this is related.
https://academic.oup.com/brain/article/148/6/1862/8052899?gu...
> “The goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation,” said Dr. S. Thomas Carmichael, the study’s lead author and professor and chair of UCLA Neurology. “Rehabilitation after stroke is limited in its actual effects because most patients cannot sustain the rehab intensity needed for stroke recovery.
Sounds truly amazing, I have known two people who had severe strokes - one's PT was contingent on triaging resources to whoever was likely to recover more, another simply hated PT and speech therapy and often refused to participate or do the exercises. Even if it didn't help recovery a medicine like this would have reduced the stress of everyone involved.
Could this treatment also help with other neurodegenerative diseases?
Do we consider strokes to be neurodegenerative? I would have expected them to be considered acute.
How do they test this on mice? Do they trigger brain seizures in them?
Many different techniques for different types of stroke:
We can block certain arteries mechanically by inserting a tool, inject photosensitive agent then cause a targeted clot with a laser, inject clotting agent, choke, inject blood vessel dissolving agent and re-inject its own blood.
I understand why we research this but I just could not do it.
I can understand.
One of our family friends just could not continue draining monkeys of blood for biochemistry research. I have been to his lab. The monkeys would panic whenever their cages were touched.
I can one needs a level of sociopathy or psychopath to continue this kind of research.
The benefits to humanity is substantial though.
So you do nothing on the trolley problem, eh?
Not to troll but it doesn't require disease to work through discomfort if you believe the outcome will be worth it.
Why not experiments on convicted criminals, inmates, prisoners of war, political prisoners ...
The line is somewhat arbitrary and personal. It makes sense to the person.
To be honest, I don't know what decision I will take if a trolley problem is jumped on me without prior notice.
As you write, we all have our own balances. I'd suggest there are ethical reasons against those.
As a society we have investigation review boards, laws, and other conventions.
There is a sizable set of people that like to outsource (want it done but not to do it) which seems dishonest, like the town butcher in Buddhism bring a bad karma sink.
Indeed.
In the particular non-hypothetical case I mentioned, the lab monkeys were a little too close to human babies in their behavior and appearance. That did not help at all.
Those who do not want partake in specific class of animal testing should also recuse themselves off the fruits of that class of experiments.
That lab sounds terrible.
In the only monkey lab I've been in, I witnessed deep mutual love between the animals and their keeper. The conditions you describe seem unnecessary.
Grey matter in the prefrontal increasing μg measurement with age.
... in male mice.
I think savvy universities want PIs who are savvy enough to realize that the point of these is to boost measurable visibility like citation count and h-index, so the headline of a news release boosting the article doesn't matter. They can always blame a copy editor for the headlines. It could read "world peace solved with moon juice." The provost would only care if it generated negative feedback. So it's the PR department's job to juice it as much as possible without getting blowback.
Isn’t that where all drugs start out? But yea the headline doesnt tell the full story
“…in mice” isn't a criticism of the science, it's a criticism of the popularization.
There are many drugs that don’t work on mice.
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It really depends on how much the company wants to invest. If it really worked, then it would be relatively straightforward for them to put together a Phase II. Not cheap, but relatively straightforward. Or at least it would have been when we had a functioning FDA
Also, the other definition in question is what the UCLA PR person means by "repairing brain damage". As far as I can tell from the paper - the "drug" part was using some neurotransmitter blockers on brain cells on a Petri dish to see if they could change gene expression or oscillatory firing patterns matching recordings in mice undergoing "physical therapy". They did not actually test to see if the stuff grew new brain cells or dendritic connections.
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People go on about this too much. Its the first step, it shows promise.
Does that mean it will neccesarily work? No, of course not. But its still exciting to see progress being made.
But it's not progress. Not really.
Mice are used only partly because they share a considerable amount of DNA with us. But they're mostly used because they're cheap. Both in financial and ethical costs.
They live for about two years, and breed in about three months. They are disposable. Over 100 million are killed each year in various labs across the country.
And for all of this, only about 5% of medicine that show positive animal results make it to market in some fashion. So basically, the best thing we can say about a mouse-tested drug is that "this most likely won't make things worse". But that's like a low bar.
I think there's some kind of fallacy where you can look at five drugs, all of which came from a pool of 100 promising candidates, then look at the next 100 candidates and say for each one individually that it is not worth celebrating. I call it the, "rounding to zero" fallacy.
In reality, if you have 100 5% chances of a cure for a previously incurable illness, you can celebrate each chance a lot.
> In reality, if you have 100 5% chances of a cure for a previously incurable illness, you can celebrate each chance a lot.
These numbers are obviously entirely made up, but its worth noting that 100 5% chances of a cure, means you have at least 1 cure with (1-(.95)^100) = 99.4% probability.
If you are curing an incurable disease with 99.4% probability, celebrating a lot would be an understatement.
In this example, they're all different diseases.
> And for all of this, only about 5% of medicine that show positive animal results make it to market in some fashion. A mildly positive result is a neccesary but not sufficient condition to make a marketable drug.
I'm surprised its that high tbh. And i suspect it would be a similar low number if we tested on humans instead of animals.
And yes, being able to test early stage ideas cheaply is critical to innovating. We use mice in biology for the same reason we use computer simulations in other fields.
Anyways, if we took your numbers of 5% chance at face value, that means there is a 1 in 20 chance of this press release turning into a real drug that saves real people's lives. Personally i dont think the chance is actually that high, but if it was that would only further my point that this is a milestone worth celebrating.
Hi, sorry, this is so disingenuous of a statement I cannot pass by it without commenting. My bona fides are 10y of lab work, specifically in bioenergetics. I can tell you that 5% is a dramatic UNDERESTIMATION on the value of animal models for medicine at large.
This is ignoring at least these benefits: surgery, development, genetic studies, grafts, anesthesia, and many MANY more. Some non-drug related, some drug adjacent, and they definitely have downstream benefits to humans.
Here's a survey paper with myriad examples: https://pmc.ncbi.nlm.nih.gov/articles/PMC9247923/
I really don't like when bioscience articles land here in HN because they are always commented on with:"in mice", as if to say nothing we see from mouse work works. Well, not everything is software and this kind of work takes years, if not decades. It is real science unfortunately which means that most of it doesn't work! Science, and bioscience specifically, are not efficient systems. In general, the things you do are hard and probably won't work. That doesn't mean you give up.
Animal models are not great, but they are the best progression we can do right now from cell models. And as for being disposable, there are controls on how animals are used in labs in the US: every institution that has animal experimentation has an IACUC (institutional animal care and use committee) that every research proposal must go through, and they do not a rubber stamp your proposal. They want to know why you can't use cell models, and why you can't do it with less or even no animals.
It would be nice if people were a bit more even handed when these types of articles come by. I think HN can do better.
An adage from the lab: "If what we did always worked it would be business, not science."
You’re right.
Let’s just skip straight to human trials.
very happy for those mice
Neuralink.
Are there any supplements that can work for neurogenesis? I've heard Lions Mane extract can do this, but I'm not sure. Anybody know of anything?
If you don't sleep 8+ hours a day every single day, exercise regularly, live in a place with clean air, eat clean food, don't drink alcohol, etc. you're losing your time, no amount of supplement will make up for our modern way of life, you're going to optimise the 0.1% while missing the 99.9% that matters
That is true, but keep in mind that routine is very difficult to do for someone that makes their living running the rat race, with stress, no time, responsibilities, worry, untreated health problems, etc. If you have the money, job security, then you'll have peace of mind. That will then allow one to live that kind of optimized lifestyle.
This is why we cannot abide scabs.
I see your point :)
Self-respect is an act of charity.
There's (minimal) research on psilocybin doing just that. One of the tragedies of prohibition is that we just weren't able to study these psychedelic compounds easily for 50+ years.
Have any sources? I’d love to read what you are thinking about.
I haven’t used psilocybin in a clinical setting but have gone through an alternative psychedelic-assisted therapy process. Very interesting results and many positives.
There's not a lot, unfortunately. This paper is a literature review and the claims are weak, but there's something there that should be investigated further: https://pmc.ncbi.nlm.nih.gov/articles/PMC12392120/
Paul Stamets has evangelized psilocybin + lions mane + niacin for years in a microdosing format, but again, the research is lacking largely due to prohibition.
Awesome. Thank you.
Not necessarily neurogenesis, but evidence of neuroplasticity: https://news.ycombinator.com/item?id=48030098
Thank you.
Not to take away from your point about psilocybin but the mushroom brought up, lions mane, is not hallucinogenic.
For sure, and lions mane is one of the three things Paul Stamets has been talking about for years to take in combination with niacin and psilocybin (microdose) to support neurogenesis. Low doses of psilocybin have only very mild perceptual changes, much less than smoking weed or drinking alcohol (for me). But again, there's not much science on it which will hopefully change.
Cardiovascular exercise and strength training. Both are thought to contribute to neurogenesis, even in healthy people
I've read online that "Bacopa Monnieri" is a particularly strong and researched herbal supplement for cognitive maintenance, enhancement and neuroprotection, with the potential of supporting neurogenesis.
I've not tried that stuff since money is hard to come by these days. There have been a few human studies.
You can find more info here:
https://pubmed.ncbi.nlm.nih.gov/?term=bacopa+monnieri+cognit...
and here:
https://www.nccih.nih.gov/health/bacopa-monnieri
https://www.swansonvitamins.com/p/swanson-superior-herbs-bac...
Thank you for the link :)
I’ve been researching potential solutions to stimulate neurogenesis, specifically looking for a combined approach that maximizes the beneficial effects of several powerful herbs while prioritizing safety and remaining affordable to the sub-middle class.
After some research and consultation with AI tools (obviously), I’ve narrowed down a promising blend of ingredients: Bacopa, Curcumin (with piperine – black pepper extract – to improve absorption), Lion’s Mane, Gotu Kola, NGF (delivered via eye drops or another method), Hericium Erinaceus, Marine Collagen, and Dimethylaminoethanol Bitartrate (DMAE).
The investigation has made it clear that truly effective neurogenesis isn’t just about boosting NGF levels. It requires a holistic strategy – carefully balancing metabolic pathways, antioxidant defenses, gut health, and inflammation modulation. Creating a supportive environment for neuronal survival, growth, and communication is key, and that includes addressing factors like stress management.
Perhaps one of the Bio-themed Tech bros on this forum might consider taking on this type of research endeavor. Or maybe there's an Eddie Morra-themed Tech bro that might have more "Limitless" how-to advice on the matter because the above to-do list is definitely, above my paygrade :)
Noopept
https://en.wikipedia.org/wiki/Omberacetam
Supposedly NGF eye drops https://www.independent.co.uk/news/science/is-this-the-secre...
Alpha-GPC and Uridine Monophosphate appear to have some effect, though minor. Also not exactly neurogenesis, but adjacent stuff. Evidence is complicated, there seems to be a signal but it's a weak effect.
Of note, cautionary tale is too much neurogenesis is brain cancer...
No, brain cancer is brain cancer.
which is poorly differentiated cells undergoing unchecked neurogenesis...
That’s like saying a fire on an oil rig is the same as combustion in a car engine
It’s not as bad an analogy as you make it sound. It is more like “fire is what makes our factories run, and oil fuels fire. So let’s douse our factories in gasoline to speed things up.”
Nicotine is the only psychoactive substance proven to increase intellectual function. Rote neurogenisis does not - much in the same way height isn’t a proxy for IQ. Stimulants like Adderall, Caffiene, etc are Dunning-Kruger by proxy.
You mean placebo? Not sure that Dunning-Kruger is applicable here
Maybe a better term is “stimulant-induced metacognitive miscalibration”. An induced a state of overconfidence similar to Dunning-Kruger - even thought the underlying mechanism is different.
You perceive the idea as great not because you suddenly understand it better or know more. You think the idea is great because of the dopamine flooding your brain. And much like Dunning-Kruger, even thought you might think you did better, real world results don’t match your expectations.
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