Researchers are looking for the best ways to improve current therapies and advance research in ischemic stroke. Ischemic stroke occurs when a blood clot blocks or narrows an artery leading to the brain. A new study in mice by the University of Pittsburgh (Pitt) demonstrates that a unique subset of white blood cells gives fast-acting and lasting protection against ischemic stroke in mice.
Their findings are reported in the Journal of Clinical Investigation in a paper titled, “Neuroprotection against ischemic stroke requires a specific class of early responder T cells in mice.”
“Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms,” wrote the researchers. “We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection.”
“The beauty of CD8+TRLs is in their fast response. They confer very potent protection to the brain, which can last a long time,” said co-corresponding author Xiaoming Hu, MD, PhD, associate professor of neurology at Pitt and a U.S. Department of Veterans Affairs (VA) investigator. “Most importantly, these cells are easily accessible because they circulate in the blood before they enter the injured brain.”
“Creating shelf-stable and ready-to-use CD8+TRLs or developing a cocktail of neuroprotective signaling molecules released by those cells once they reach the brain could present effective future therapies against stroke and offer hope to hundreds of thousands of patients who are ineligible for treatments available to them currently,” said co-senior author Jun Chen, MD, PhD, professor of neurology at Pitt and a U.S. Department of VA investigator.
The researchers showed for the first time, that the CD8+TRLs enter the brain much faster than any other regulatory immune cells. Within 24 hours after researchers depleted these special CD8+TRLs from the bloodstream of stroke mice, the size of the brain region affected by ischemia expanded by 50% compared to animals whose CD8+TRL levels remained intact.
The researchers also observed that mice who received a transfusion of purified CD8+TRLs prepared in the lab fared better and recovered faster than those who were untreated for over five weeks.
“Despite the efforts of thousands of people devoting their careers to finding treatments that could benefit stroke patients, therapy options are minimal,” said Chen. “I have been working in this field for more than 30 years, and this is the first time I feel that I am seeing the light at the end of the tunnel, promising future clinical translation that will benefit patients.”