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These Fast-acting Immune Cells Can Protect Our Brain After Stroke Onset – Says New Study

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Neurologists and immunologists from the University of Pittsburgh reported today in the Journal of Clinical Investigation that a unique group of white blood cells protects mice against ischemic strokes quickly and for a long time.

A new subset of CD8+ regulatory-like T cells, known as CD8+TRLs, has been discovered as the “first responders” to stroke in this study. The dying brain cells send out a unique “homing” signal that draws CD8+TRLs to the site of ischemic injury. Within 24 hours of the start of a stroke, CD8+TRLs reach the brain, where they release molecules that protect neurons directly and stop inflammation and secondary brain damage.

“The beauty of CD8+TRLs is in their fast response. They confer very potent protection to the brain, which can last a long time,” says co-corresponding author Xiaoming Hu. “Most importantly, these cells are easily accessible because they circulate in the blood before they enter the injured brain.”

According to co-senior author Jun Chen, “developing 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.”

Brain regions affected by ischemia in stroke mice

Every year, 800,000 Americans suffer from stroke, yet only 25% of those people will be qualified to receive one of the two FDA-approved treatments: tPA injections or mechanical thrombectomy, a surgical treatment in which the blood clot in the brain is removed with a stent retriever.

Many patients, especially those who live in country areas, are ineligible for those therapies since they must be given very soon after the stroke. The 600,000 people who are still living are treated symptomatically and are at a high risk of long-term health issues, such as mobility issues and, in some cases, speech and cognitive disorders. In addition to this, the therapy that breaks up blood clots in particular has some downsides, which further reduces the number of people who can benefit from such a therapy.

The immune system has a significant impact on stroke. When a blood clot gets stuck in a blood vessel, the brain sends a “SOS” signal to the immune system to start working. This quick immune reaction seeks to eliminate cell remnants, reduce brain injury, and jump-start repair procedures. However, the immune system’s functions are complex and diverse, and certain immune cell types may have specific advantageous or harmful effects on a damaged brain.

Chen, Hu, and their colleagues showed for the first time that CD8+TRLs get into the brain much faster than any other regulatory immune cells. The size of the area of the brain affected by ischemia in stroke mice increased by 50% within 24 hours of researchers depleting these particular CD8+TRLs from the bloodstream.

More encouragingly, mice who received a transfusion of lab-purified CD8+TRLs performed better and recovered more quickly than those who went untreated for more than five weeks. Therefore, these distinct CD8+TRLs function as early responders to mobilize defenses following stroke and may team up with other immune cells to preserve the brain for a considerable amount of time.

“Despite the efforts of thousands of people devoting their careers to finding treatments that could benefit stroke patients, therapy options are minimal,” adds 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.”

Image Credit: XIAOMING HU

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