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Researchers looking for new ways to treat human brain injuries and other cognitive disorders are finding answers.

Studying, hibernating, Arctic ground squirrels.

The optimal therapy for somebody who has a brain injury is to either stop fever or to cool the body.

And the best way to do that is through the same mechanism that the ground squirrels do to turn down the thermostat.

We'll hear from scientists about these and other medical breakthroughs that could come from understanding the extremes of hibernation.

Right now on Alaska, insight.

Good evening.

Hibernation is an incredible biological process undergone by countless species across the planet.

Alaska is home to a number of animals that hibernate.

And today, we'll discuss how work to understand these processes is and can be applied to human medicine.

But before we get to that discussion, we'll start off with some of the top stories of the week from Alaska Public Media's collaborative Statewide News Network.

The Biden administration has approved the Willow Development, a major ConocoPhillips project in the National Petroleum Reserve on Alaska's North Slope.

The decision comes after a contentious battle over the project's approval.

Alaska's congressional delegation and state leaders were united in supporting the project, along with numerous Alaska Native corporations and organizations in the Arctic.

While conservation groups, as well as the city and tribe of New Exit, the closest community to the project, were opposed.

Conservation groups filed a lawsuit Tuesday against the federal government seeking to stop the project.

The American Civil Liberties Union has filed a lawsuit against the Alaska Department of Corrections for the second time this year.

The new lawsuit alleges that the doc has been forcing a man serving prison time in Seward to take psychotropic medications against his will for years, well beyond their legal authority.

The ACLU is asking the court to let the man mark Andrew's get due process to properly argue against being medicated and to strike down the corrections policy on involuntary medication as unconstitutional.

Department of Law spokesperson Patti Sullivan says by email to Alaska Public Media that one of its attorneys will respond to the suit through the court process.

And Anchorage's municipal election is now underway.

With nearly 200,000 ballots mailed to registered voters this week, the ballots are long this year, with questions on some filling up all four sides of two ballot cards.

The mix of questions varies from area to area and includes Anchorage Assembly and school board races, plus 15 ballot propositions.

Ballots can be mailed, dropped at a secure drop box or left at one of the municipalities vote centers on or before April 4th.

For more information on the candidates, you can find our candidate comparison tool as well as the full versions of these stories and many more on our website.

Alaska Public dot org.

Or by downloading the Alaska Public Media app on your phone.

Now on to our discussion for this evening, the ongoing research into hibernation and the potential for applications in human medicine.

Arctic ground squirrels are extreme hibernate.

They can take their body temperatures to freezing levels and can stay dormant for up to eight months.

Researchers at the University of Alaska, Fairbanks, are studying these tiny creatures to understand how their bodies can survive on the edge of life.

And as Alaska Public Media's Kavitha George reports, the squirrels may hold clues to treating injuries, fighting aging and curing diseases in humans.

This this little squirrel just came out of the freezer, but it's not dead.

And scientists like Sarah Rice want to know why there's no cardiac arrest, There's no stroke.

They're obese, but there's no ill effects.

There's no bone loss.

This is an Arctic Ground's world, and during hibernation, it can chill its body down to the freezing point, 32 degrees Fahrenheit.

It's the only mammal that we know can get that cold and they wake up and they're just fine in the springtime.

Here at the university of Alaska, Fairbanks, researchers are trying to understand the biological mechanisms that allow squirrels to withstand such extreme conditions and bounce back completely healthy.

They found that when the squirrels hibernate, they cycle in and out of a deep sleep called torpor.

They're in torpor for weeks at a time where their super, super cold, the heart beats maybe five times a minute.

They breathe once a minute and they're just inactive.

Arctic ground squirrels are found all over Alaska, Siberia, and parts of Canada.

They hibernate because harsh winters limit their ability to find food for much of the year.

But every few weeks, they slowly warm their bodies to make glucose, proteins and immune cells.

Basically, everything their bodies need to do to keep living.

So how do they do it?

If researchers here can figure it out, it might help them develop drugs that could mimic hibernation in humans.

Biologist Kelly Drew says hibernation might help patients with critical brain injuries, like someone who's just had a stroke.

The optimal therapy for somebody who has a brain injury is to either stop fever or to cool the body.

And the best way to do that is through the same mechanism that the ground squirrels do to turn down the thermostat.

Drew's small team of scientists is working on creating a drug to chemically turn down the body's thermostat like squirrels do in hibernation.

They're focused on certain receptors in the brain called adenosine A1.

Our hope is that a drug that stimulates A1 receptors in human brains could be part of an effective treatment for stroke or other brain injuries or even promote brain health as we age.

The other thing that cooling and rewarming does to the brain is it also creates these regeneration of synapses and maybe even neurons.

And so for things like mental.

Health.

I think cooling and rewarming could be remarkable because it promotes plasticity.

Same with neurodegenerative diseases like Alzheimer's.

So far, Drew says, the drug has shown promising results in rats and pigs.

The drug testing process is long and rigorous.

If it works, it could be 5 to 10 years before it has final FDA approval for human use.

Drew says NASA has even shown an interest in the potential to put astronauts in a hibernation like state to aid space travel.

The seven month trip to Mars would be a lot more pleasant in a hibernation bubble for Alaska.

Insight, I'm Kavitha.

George.

Joining me tonight to help us better understand the hibernation research and how that science may help humans in the future is Dr. Kelly Drew.

Dr. Drew is the director of the Center for Transformative Research and Metabolism at the University of Alaska Fairbanks.

And I was just in the video we saw.

And Dr. Oivind Toien, or even Toien is a research assistant professor at UAF Institute of Arctic Biology.

Welcome, both of you for being with us this evening.

And Dr. Drew, I want to start with you.

When did this research with Arctic grown squirrels start and how surprising were the findings that these small animals can drop to freezing temperatures yet suffer no damage?

Of research on hibernation has been happening here in Alaska for over 60 years.

Most of it is conducted by people, physiological ecologist, we call them.

They're biologists that are interested in animal adaptations.

And so Brian Burns, I think it was 1989, he published a paper in Science that showed that the ground squirrels can drop their body temperature below freezing.

But his work builds on decades of work here in Fairbanks.

So that's the exciting thing.

And I think what really adds rigor to the biomedical applications is that the long, many years of basic science, understanding what the animals do and their physiology in somewhat of a descriptive way.

But now we understand that.

So we can say, Wow, they know how to do that.

I guess if we knew how to do that, we could use that for human applications.

And breaking down the centers research.

You study hibernation to learn what's happening in the body during that state to see how it might apply to human medicine.

Humans aren't hibernate.

So how could the hibernation offer help to humans?

Well, there's a number of things.

You know, the original The first application is for critical care, particularly to protect the brain.

But there's the adaptations are so relevant to things like obesity and aging, like the video referred to.

So it's really the process of rewarming from hibernation, where a lot of the plasticity happens for brain and regeneration.

And then the aspect of going into hibernation is all regulated by this seasonal reprograming of metabolism.

So that seasonal reprograming allows the animals to get fat prior to hibernation.

And understanding those mechanisms could certainly be applied to humans because if you understand how they get fat, then you understand how the brain promotes fattening and then you can reverse that if you don't want to be fat.

So there's just a lot of applications.

And what else did I miss or even.

Well, I wanted to to to turn to you, Dr. Toein.

And when when Dr. Drew was talking about fat, I immediately think of bears, because we know that bears get pretty fat when they go to hibernate.

You study the physiology of animals, mostly bears.

Describe what that involves and what in particular you're studying with bear hibernation.

Thank you.

We are particularly interested in how bears suppress metabolism.

The difference between bears and articles is we think that both it's important to study both.

But.

But bears have and are hibernating at a temperature that is much closer to what a normal human would have.

And thereby we do not have all the complications by managing a very low body temperature so that they still suppress their metabolism metabolism.

That's the process that sustains life and consumes oxygen.

And in many clinical cases, like cardiac arrest and stroke, the oxygen supply to the tissues have been restricted and locked and thereby.

But if we can then decrease the amount of the oxygen consumed by the tissues, then one could avoid injury and improve the outcome much better.

What level of cold can there survive compared to Arctic ground squirrels?

That's a great question, but what we do know that is that bears they seldom want to go well, we are scientists, I would say 30 degrees C, but they normally hibernate at a temperature of about 90 Fahrenheit.

So that's the average.

But they actually have very they have all day temperature and costly through hibernation.

So it's not a stable temperature, actually.

But but that's a lot more moderate.

We know they can tolerate low temperature before they go into it and get problems like getting cardiac arrest.

There were some early experiments.

And then on bears that are going to be euthanized and they didn't get caught.

Areas below before it got down to about 25 degrees C, so about ten degrees, ten Fahrenheit lower than sort of 24 net lower actually than would be normal for a bear, actually.

So they are much more tolerant to low temperatures.

So nice.

But still they cannot go down to the low temperatures set and articulate.

And if you are going to use cooling and rewarming for in these human applications for treatments of injuries or or stroke, heart attack, is it a figuring out how to have a drug that recreates what's happening rather than actually cooling people down and rewarming them?

Because that would take quite a bit of conditioning, wouldn't it?

So for the humans to be able to reach that low temperature.

Yeah, that's all it takes time for sure.

And so if we have a drug that works as a cellular level and could almost instantly decrease metabolism, that could be a very efficient treatment, actually, theoretically.

Of course, we don't have that term at the moment.

Dr. Drew, pick it up there.

Let's talk a little bit about the fact that ground squirrels don't suffer tissue damage when their temperatures drop below 32 degrees.

And could understanding this help with frostbite treatment in humans in the future?

Is it is it well understood why their tissues don't suffer damage?

Now, that's an area that is wide open that we have not had the bandwidth to tackle yet.

But it's a really good question.

The you know, the other question, you know, kind of that we've been talking about and the comparison with bears is that, you know, the ground squirrels are the fundamental feature of hibernation is they turn down their thermostat when they enter hibernation.

And then the ground squirrels get so cold that the low temperature contributes to that metabolic suppression.

Bears don't get so cold, so they offer the opportunity to identify by other mechanisms in addition to cold that contribute to the metabolic suppression.

And what that ultimately amounts to is taking away the side effects when you do cool people.

So cooling is already standard of care for critical care, for neuro critical care.

If you've had a cardiac arrest.

Standard of care is too cool for 24 hours.

So babies that are born with inadequate oxygen delivery are cool for three days down to the level that a bear will tolerate.

So about the same.

But that cooling, particularly in adult humans, causes a lot of complications that physicians have to struggle with, and it decreases the safety of cooling.

So this ability to coordinate that cooling rather than forcing it is expected to be beneficial.

Right now, there's a lot of controversy over cooling because of these side effects and some life threatening side effects.

So there have been clinical trials that suggest the benefit is not as great as what was first thought, although we know lots of examples.

For example, people who drown in cold water can be literally dead for hours and revived with minimal neurologic deficit, if none.

So it's just a matter of of being able to coordinate the processes in a way that the body can tolerate and and so this is the start.

So some of the work I do in or even has participated is looking at how the brain regulates this.

But then you can also look at the cellular level outside the brain and find other mechanisms.

And those are the ones that have not fully been identified.

And beyond heart attack and stroke described the prospects for addressing mental health concerns like PTSD.

What are you learning that could offer help for people experiencing trauma?

Well, you know, trauma and mental health often has to do with the the brain plasticity, what synapses are formed, what networks are active in ways that are not productive.

And so if you can rewire the brain, that could be protective, even with depression and antidepressant drugs, you know, they promote new neurons.

And so these processes that promote plasticity, new neuron growth and new synapses and new and rewiring can potentially be helpful for for mental health.

And another thing these animals do, both ground squirrels and bears, is they have this regenerative process properties not only in brain but also in muscle and potentially in bone.

So like or even referred to or I think the video referred to is they they don't eat or drink and they don't move for the hibernation season yet they wake up strong.

So this is also potentially relevant to treat frailty and sarcopenia.

These are two issues with aging.

And Alaska has the fastest growing aging population per capita than any other state.

So it really is a big challenge for Alaska because of the cost of long term care.

When people are affected by Alzheimer's or sarcopenia is loss of muscle with aging that can really contribute to frailty and other associated conditions.

So that's another application that we are working on here.

So I apologize.

So many exciting prospects for the future.

The ground squirrels get fat before they hibernate and they become insulin resistant.

Then after hibernation, they lose the fat.

Their insulin resistance is triggered.

Can you translate that into how that insulin process works for healthy humans?

And what could this research mean for treatment for diabetics?

Yeah, that's exactly it.

So we don't know we don't know anything about how they change their insulin sensitivity.

But if we did know that, absolutely, there would be a way to use that for therapeutics.

And part of it is if you understand how they do it, then you find the molecules in the body that are involved and then you can target those molecules with potential therapeutics.

So generally you take a big drug library of molecules you think would be relevant and then you screen against that.

So it's also understanding how they do it can develop into drug screening platforms to identify novel therapeutics.

Usually science, if I understand it correctly, is trying to disprove things challenging new theories and assumptions to see if they fall apart.

But this research sounds like it's more like solution science, studying what's working in animals and seeing how that might be applied to human health.

If I'm characterizing that correctly.

Is this a new approach and how do you see it expanding into other areas of medicine?

Yeah, it's absolutely a new approach, yet it's not really that new.

A couple of examples are like Velcro came about by understanding learning how bees the structure on the bees legs collect honey or collect pollen.

And then another example is the vampire bat that when the vampire bats, they drain blood out of their prey and they have enzymes in their saliva that prevents blood from clotting.

And those have been developed now for anti-clotting drugs.

So it's not completely new, but it certainly is it is still novel in terms of actual drug discovery, as is looking at how something is the problem has already been solved in these animals.

And so it's much easier to identify what already works rather than trying to look at a broken system and figure out how to fix it.

All right.

Thank you for that, Dr. Twin.

I want to turn to you now.

You had mentioned in an earlier interview that hibernation might be a basic part of an organism that has sort of gotten lost and doesn't function in animals that don't hibernate.

Why would this be part of the basic makeup?

And what species is this dominant function found in?

It's found among a very wide class of different animals.

And that's the reason why we say that it might be a very basic thing that could have existed from the very beginning.

You know, animals to start with were extra term, which means that they are following their body temperature, does not is not kept at a constant level, but it's all over the environment.

So and only in evolution do that because some animals become what they call wholemeal terms, which means we actually regulate body temperature at that level.

So so it is possible that they have the ability to harmonize is something that is rather lost among a number of animals than that something that's invented.

But that could it could also that's the in science.

There is also the concept of parallel evolution that the same thing could have evolved multiple times, but it seems rather unlikely that it's happened in so many different classes of animals on their own that most that hibernates are also primates, actually.

So I was just going to ask about that, that there are primates that hibernate.

Also tell us about which primates do and are you studying them in relation to humans?

The over colleagues.

I've been studying small lemurs in Madagascar, actually, and they hibernate in small tree trunks that can vary in size.

Some of them are in in because that older tree trunks are not too skinny and will vary with the temperature.

And the interesting other these lemurs have a vast array of different body temperature patterns.

Some of them will stay at a very constant level that looks like our to ground squirrel doesn't stay down indeed the whole time, but real arrows at regular intervals like every 2 to 3 weeks.

And we think that there are some restorative processes that has to happen during these arousal episodes.

Of them, ones that live in tree trunks that will vary with ambient temperature.

Well, actually, that actually goes about 30 degrees C, which is a level that the bears are at.

They will not.

So these are also the episodes that will just keep fluctuating their body temperature.

It on a daily time.

And we only have a few seconds left here.

I just wanted to ask about the prospect for the potential of perhaps a some sort of synthy torpor state where humans could be put in that in treatment for certain illnesses or injury or for sending astronauts into space.

Is that at all possible?

Well, I mean, that's what I'm working on primarily.

And it's I think it's I think it's going to be possible.

But but really the important point to understand is that as we peel these things off of what hibernation is, it's we're peeling these one at a time.

Hibernation is a very whole animal systems phenomenon.

And I think as we continue to study it, we'll understand that better.

And hopefully one day we'll be able to mimic the whole thing.

Well, thank you so much.

Thanks to both of you for being here.

As you heard this evening, the research into the physiological processes happening during animal hibernation may help humans live better lives in the future through innovative wound disease and trauma treatments.

And the prospect of synthetic torpor or an induced deep sleep state may also aid human space travel, making it safer and less traumatic for the astronauts.

That's it for this edition of Alaska INSIGHT.

Visit our website.

Alaska Public dot org for breaking news and reports from our partner stations across the state.

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Thanks for joining us this evening.

I'm Lori Townsend.

Good night.