Squirrel biology may hold an unlikely fix for avoiding brain damage in stroke patients

On paper, there’s next to nothing we can learn from squirrels. Barring an appetite for nuts, there seems to be precious little we have in common – but it’s this sense of difference which may offer an unlikely lifeline to stroke patients.

When squirrels hibernate, scientists from the National Institute of Neurological Disorders and Stroke (NINDS) discovered, a cellular process called SUMOylation accelerates, offering protection to the squirrel brains. Brain cells which would normally whither and die when deprived of their usual blood flow survive the full length of the hibernation period.

Most strokes are caused by a blood clot which prevents oxygenated blood from reaching the brain. Doctors operating on stroke patients have to remove the clot as quickly as possible – the longer they take, the more likely it is for brain cells to have died, and for the sufferer to live with permanent disability if they survive at all. Of the 100,000 or so people who have strokes in the UK every year, around two thirds will leave hospital with some kind of disability.

By mimicking the squirrel hibernation process, the researchers reasoned, could they buy the doctors more time to work on the clot without consequences for the patient’s health?

“If we could only turn on the process hibernators appear to use to protect their brains, we could help protect the brain during a stroke and ultimately help people recover,” said study author Joshua Bernstock, a graduate student at NINDS.

And that’s what the researchers discovered – at least in animals. From an initial list of 4,000 molecules, the team used computer modelling and further tests to narrow the shortlist down to eight which might help kickstart the SUMOylation process. Of these, two were found to boost SUMOylation in rat cells, while keeping the brains alive in the absence of oxygen and glucose: an enzyme called ebselen and 6-thioguanine.

As the latter is a chemotherapy drug with known side effects, ebselen was selected – and it successfully made the jump from rats to mice, successfully boosting the SUMOylation process in the rodents with an injection to the brain.

“For decades scientists have been searching for an effective brain-protecting stroke therapy to no avail,” explained Dr Francesca Bosetti, program director at NINDS.
“If the compound identified in this study successfully reduces tissue death and improves recovery in further experiments, it could lead to new approaches for preserving brain cells after an ischemic stroke.”
This could be an enormous breakthrough, though as ever rodent brains offer a very different experience to human ones. All the same, it’s hard not to be hopeful. “As a physician-scientist, I really like to work on projects that have clear relevance for patients,” Bernstock said.

“I always want outcomes that can lend themselves to new therapeutics for people who are in need.”