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.
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 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:
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.
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.
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.
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.
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.
"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.
> 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.
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.
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.
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.
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.”
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.
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.
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.
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.
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.
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.
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.
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
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?
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.
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...
Could this treatment also help with other neurodegenerative diseases?
> “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.
> 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.
... 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.
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.
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.
Not to take away from your point about psilocybin but the mushroom brought up, lions mane, is not hallucinogenic.
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.
Not necessarily neurogenesis, but evidence of neuroplasticity: https://news.ycombinator.com/item?id=48030098
Cardiovascular exercise and strength training. Both are thought to contribute to neurogenesis, even in healthy people
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.”
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
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.