Clots that restrict the flow of blood to the brain cause ischemic stroke. Even after a clot is gone, about half of capillaries remain constricted—at least in mice—even though blood flow is restored in larger vessels. Researchers have found that free radicals in blood vessels lead to this constriction. That discovery may help pinpoint a new treatment target for ischemic stroke, the most common type.
“Since adequate oxygen supply is critically important to the brain tissue trying to recover from the ischemic episode, we decided to study what caused these constrictions and how it could be relieved,” says researcher Turgay Dalkara of Hacettepe University in Turkey. Their findings were published online Aug. 30 in Nature Medicine.
The investigators focused on pericytes. Located in capillary walls, these cells regulate capillary flow by contracting and relaxing. The researchers used high-powered microscopes to study mouse retinas, which have capillaries rich with pericytes. When they created ischemia-like conditions in the retinas, the pericytes remained contracted for hours after blood flow was restored in other vessels.
“Pericytes were not known to play such a negative but important role before,” says Dalkara. The researchers observed a similar effect in anesthetized mice after marking capillaries with molecules that glowed under the ultraviolet light of a fluorescence microscope.
The sustained pericyte constriction was caused by free radicals produced in blood vessel walls. “Oxygen and nitrogen radicals are very toxic,” Dalkara says. He notes that when blood flow is restored in vessels larger than capillaries, free radicals are produced in excess amounts.
The researchers addressed that problem by injecting the mice with chemicals that suppress the production of the free radicals. When they prevented that toxicity, the pericytes relaxed and allowed blood to flow through the capillaries.
After a stroke, that increased oxygen supply could be crucial for brain tissue survival. “We want to develop methods to study the problem in stroke patients with the available imaging technologies,” says Dalkara. “But it seems not an easy task.”