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.
jmalicki 34 minutes ago [-]
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:
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.
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.
asdff 2 hours ago [-]
There is nothing to resurrect. They get digested by the microglia.
steve_taylor 3 hours ago [-]
Perhaps, but I think that by the time we're that far advanced, strokes will be entirely preventable.
OneDeuxTriSeiGo 2 hours ago [-]
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.
MattCruikshank 7 hours ago [-]
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.
jadbox 6 hours ago [-]
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.
TheGRS 6 hours ago [-]
I just read this a few months ago and it was my first thought as well! Like Flowers for Algernon taken to its extremes.
naxios_official 7 hours ago [-]
[flagged]
hank2000 2 hours ago [-]
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.
"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."
> “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.
nose 4 hours ago [-]
Could this treatment also help with other neurodegenerative diseases?
0xWTF 7 hours ago [-]
... 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.
somewhatgoated 7 hours ago [-]
Isn’t that where all drugs start out?
But yea the headline doesnt tell the full story
cwillu 3 hours ago [-]
“…in mice” isn't a criticism of the science, it's a criticism of the popularization.
martinbfine 2 hours ago [-]
Neuralink.
KnuthIsGod 7 hours ago [-]
Potentially life changing for male mice...
bawolff 7 hours ago [-]
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.
bena 6 hours ago [-]
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.
whatshisface 4 hours ago [-]
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.
bawolff 1 hours ago [-]
> 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.
bawolff 3 hours ago [-]
> 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.
anarticle 2 hours ago [-]
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."
650REDHAIR 7 hours ago [-]
You’re right.
Let’s just skip straight to human trials.
functionmouse 7 hours ago [-]
very happy for those mice
nubg 7 hours ago [-]
How do they test this on mice? Do they trigger brain seizures in them?
Traubenfuchs 6 hours ago [-]
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.
trhway 5 hours ago [-]
> 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.
seabass-salmon 8 hours ago [-]
[dead]
caycep 7 hours ago [-]
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.
dirtbagskier 8 hours ago [-]
[dead]
mlmonkey 8 hours ago [-]
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?
toasty228 8 hours ago [-]
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
SilentM68 7 hours ago [-]
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.
rexpop 7 hours ago [-]
This is why we cannot abide scabs.
SilentM68 3 hours ago [-]
I see your point :)
rexpop 3 hours ago [-]
Self-respect is an act of charity.
throwforfeds 8 hours ago [-]
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.
grvdrm 6 hours ago [-]
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.
caycep 7 hours ago [-]
Of note, cautionary tale is too much neurogenesis is brain cancer...
dymk 7 hours ago [-]
No, brain cancer is brain cancer.
caycep 5 hours ago [-]
which is poorly differentiated cells undergoing unchecked neurogenesis...
1 hours ago [-]
SilentM68 3 hours ago [-]
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.
oharapj 1 hours ago [-]
You mean placebo? Not sure that Dunning-Kruger is applicable here
sysreq_ 8 minutes ago [-]
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.
contingencies 3 hours ago [-]
[flagged]
Rendered at 04:10:13 GMT+0000 (Coordinated Universal Time) with Vercel.
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.
https://www.cbc.ca/radio/asithappens/as-it-happens-thursday-...
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...
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.
https://academic.oup.com/brain/article/148/6/1862/8052899?gu...
"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
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.
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.
Does that mean it will neccesarily work? No, of course not. But its still exciting to see progress being made.
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.
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.
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.
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."
Let’s just skip straight to human trials.
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.
>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.
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.
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.
https://en.wikipedia.org/wiki/Omberacetam
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
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.