Adropin treatment shows promise to limit post-stroke brain damage in mouse study

By Michelle Jaffee

University of Florida neuroscientists have identified a new potential way to minimize brain damage caused by ischemic stroke: treatment using a synthetic form of adropin, a molecule naturally produced in mammals. Findings from the preclinical mouse-model study, published today in the journal Stroke, offer hope of adding to limited treatment options to thwart the worst effects of stroke.

portrait of doctor candelario-jalil
Eduardo Candelario-Jalil, Ph.D.

As stroke is most common in the elderly, the research team tested adropin on mice in an advanced stage of lifespan in an effort to make the method more translational to humans in future clinical trials, said senior author Eduardo Candelario-Jalil, Ph.D., an associate professor in UF’s department of neuroscience.

Ischemic stroke, the most common type of stroke, happens when blood flow in an artery supplying the brain is blocked by a blood clot or fatty deposits called atherosclerotic plaques. Adropin is a peptide, or a short chain of amino acids, discovered in 2008 and highly expressed in the brain; in normal aging, levels of adropin in the brain and plasma drop significantly, Candelario-Jalil said.

In the new paper, researchers tested the effects of adropin through two approaches: by altering the gene that encodes the natural form of adropin and also by delivering a synthetic version of the hormone intravenously.

“We found that treatment with adropin at the onset of reperfusion [restoration of blood flow] significantly reduced the amount of tissue that dies after a stroke,” Candelario-Jalil said. And more importantly, the animals performed better on sensorimotor and cognitive tests and recovery was faster in the adropintreated mice.”

With stroke, the quicker the intervention, the more tissue may be saved and the better chance of recovery or of limiting disability. There are two main current treatment options: a clot-busting drug called tissue plasminogen activator, or tPA, given by IV to eligible patients who arrive at a hospital within 3 tohours of a stroke; or surgery to remove or break up the clot.

In the new study, researchers examined the effects of adropin in mice aged 18 to 24 months after transient middle cerebral artery occlusion, a widely used model in experimental stroke studies. For the first approach, aimed at understanding the mechanism of adropin, they genetically deleted the gene that encodes it, resulting in a significant increase in tissue death and worsened neurological function. Conversely, when they increased the expression of adropin, they saw a dramatic preservation of tissue, they reported.

In another set of experiments, researchers delivered synthetic adropin in sync with restoring blood flow, mimicking the scenario of a stroke patient who has a clot removed either through tPA or surgery. They injected adropin four hours after stroke onset and found a significant reduction in tissue death and preservation of muscular strength and cognitive function, according to the paper.

Overall, the study is important because it unveils a novel protective role of a peptide that is endogenously produced, and that’s important because it could become like insulin for a stroke,a peptide that is biologically made in your body but somehow with aging and stroke is lost,” Candelario-Jalil said. “It’s a mechanism we don’t fully understand yet, but we hope we can actually reduce the susceptibility of the brain to stroke.”

He said the next step in this line of research is to investigate whether adropin confers protection in animal models of ischemic stroke with comorbidities such as diabetes and hypertension, which are conditions commonly seen in stroke patients. Rigorous testing of adropin’s effects in preclinical animal models is needed to precede any future human clinical trials of the novel therapy.    

Read the article in Stroke.