This predictable and orderly process stands in stark contrast to the biological chaos that ensues when a person suffers an ischemic stroke.
When human brain tissues are suddenly starved of blood and the oxygen it carries, neurons respond by releasing large quantities of neurotransmitters.
To limit the impact of a stroke and its aftermath, time is of the essence—treatment can succeed only if symptoms are recognized quickly and a patient can be rushed to a hospital equipped to treat stroke patients rapidly and well. To stop this cascade of destruction, physicians have three options—administer a drug called tissue plasminogen activator to break up the clot, remove it with clot retriever devices, or use both of the above treatments.
These approaches can restore blood flow and a supply of life-saving oxygen to the brain. But the more time that has passed, the worse the ischemic and reperfusion injuries are when the blood returns, as the immune system unleashes immune cells called microglia that hurt healthy parts of the brain in their efforts to repair damaged tissue. She and her colleagues used a needle-thin probe to create tiny brain injuries—the closest simulation they could manage—both in Arctic ground squirrels that were hibernating and in those that were awake.
Brain tissue in normal-temperature squirrels showed a cascade of damage and an inflammatory response in the tissue surrounding the probe, much like what happens to a person who has a stroke.
But the intentional injury had significantly less impact in hibernating animals. Drew surmised that Arctic ground squirrels in this state are helped by some sort of neuroprotective compound. Hjalmar Bouma , a pharmacologist and resident in acute internal medicine at the University of Groningen in the Netherlands, discovered what that compound might be—and is investigating it for clinical applications to protect against organ injury and conditions such as sepsis.
As a medical student, Bouma had worked in the lab of Robert Henning , an anesthesiologist and pharmacologist at the university who was interested in hibernation as a way to protect organs during major surgery. For their experiments, Henning and Bouma used the Syrian hamster, a hibernating rodent native to the Middle East. The researchers compared hamster cells to kidney cells from rats as both sets of cells were chilled and rewarmed, simulating hypothermia and reperfusion.
The first clue about what set hibernating animals apart was olfactory. Bouma guessed immediately that the smell meant the presence of hydrogen sulfide. All of those foul-smelling cells survived for 24 hours after being chilled and thawed, while only half of the rat kidney cells lived that long. When the researchers added hydrogen sulfide to the rat cells, the chemical blunted the harmful effects of reperfusion in those cells as well. Not coincidentally in this context, oxidative stress also causes much of the damage during reperfusion after a stroke, adding to the effects of an overactive immune response.
But Syrian hamsters and other hibernators, including lined ground squirrels a cousin of the Arctic ground squirrel , produce hydrogen sulfide in abundance, and Bouma hypothesized that its purpose could be to protect cells from oxidative stress. Other studies added credence to that hypothesis. In her lab at the University of Wisconsin, Carey found evidence of oxidative stress in hibernating lined ground squirrels.
Arctic Ground Squirrel. But humans tend to shiver violently to maintain a normal body temperature, and shivering is a calorically expensive process that requires extra oxygen—just when, during a stroke, cells are oxygen-starved.
Reducing body temperature thus puts an even greater strain on metabolism and could make stroke damage worse. A second possibility would be to imitate the immune system changes that occur during hibernation. Moreover, the researchers also noted that these white blood cells have a reduced function, leading to a broader immunosuppression that affected all parts of the immune system and which may, in addition to the effect of hydrogen sulphide, serve to protect against organ injury. Tamping down the immune system might also help protect human patients, suppressing the collateral damage caused by overenthusiastic microglia immune cells, which attempt to clean up a stroke injury and hurt healthy cells in the process, says Mihai Podgoreanu , an anesthesiologist at Duke University.
But it could also leave patients at a higher risk of developing secondary infections. European Lesser Horseshoe Bat. Massive air conditions roar, blowing cold air over the rows and rows of cages. Using a red-tinted flashlight, he opens one up, and pulls out a plastic drawer. Inside, curled in a ball, packed in cotton, is a squirrel. It's cold to the touch, as Grahn picks it up, and places it on my palm. It feels more dead than alive. That condition interests the military, because if wounded soldiers could somehow be put in a squirrel-like state, their wounds would essentially stop bleeding; even seriously-injured patients could be kept alive for much, much longer.
Ordinarily, those wounds are enough to kill a rodent in 30 minutes or less. Cool stuff. But the problem, explains Hannah Carey , a professor at Wisconsin's School of Veterinary Medicine, is that no one has quite figured out exactly how the critters are pulling it off. Glucose-munching mitochondria, used to operating at very low levels, get all discombobulated, when they get a full meal, again.
When oxygen-deprived tissues start getting their 0 2 again, all kinds of nasty free radicals follow. They have this endogenous clock in their brain that tells them what time of year it is. This is likely for triggering their end of torpor: that reduced metabolism period.
But we also see a tremendous amount of plasticity when they actually emerge to the surface. And so we are interested in understanding how they determine what conditions are like on the surface when they are sequestered in their hibernacula with a meter of snow above them. Based on gender and age, Arctic ground squirrels select an extremely precise time to enter hibernation immergence chronology and to end hibernation emergence chronology.
Adult females enter hibernation before the end of July; meanwhile, their male counterparts continue to squirrel away food in a burrow, entering hibernation no later than October 1st. The males will awaken from hibernation earliest in the spring; to be reproductively competent they need to go through puberty every year, eating the extra food cached away in their burrow and undergoing testicular maturation. Females come to high body temperature say on the 28th of April, something like that, and come right above ground and they are impregnated within 24 hours.
They end hibernation. Gestation occurs over the next 25 days or so and then they move into lactation. And as soon as they gain back their body mass in July they enter hibernation.
Too cute. And that is unique across all hibernators and unique among vertebrates. We go ischemic which means the blood stops flowing or hypoxic not enough oxygen. In a human, or a rat for that matter, if you induce those same circumstances there will be terrible damage in just 5 to 10 minutes. Your heart will begin to die. We want to know how. During hibernation, everything slows down.
They might breathe only every few minutes. So Arctic ground squirrels are quite unique in that they have to generate heat to prevent themselves from freezing; they still do use a fairly substantial amount of energy. Arctic ground squirrels have adapted to live in the Arctic tundra and permafrost. That means to maintain a core temperature of
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