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Muting an inflammatory loudspeaker on immune cells shrinks acute stroke damage

Selectively subduing a set of cells that migrate to the brain after a stroke occurs could meaningfully treat the stroke even days later.

Selectively turning down the volume of a "siren" that spurs some angry immune cells to migrate into the brain soon after a stroke could meaningfully reduce symptoms, even days after the stroke
occurs, according to a study in Nature Immunology conducted by neuroscientist Kati Andreasson, MD, and her colleagues.

When the researchers suppressed the activity of a small set of immune cells in mice who'd had strokes, they saw what we'd all like to see more of after such an event: substantially reduced brain damage, better survival rates, and improved motor performance days later. From my news release about the study:

'This new approach worked,' Andreasson said. 'It might mean we can prevent a lot of the brain damage and functional losses that occur after a stroke just by targeting the immune response instead of damaged nerve cells or blood vessels.'

Strokes are the leading cause of disability in the United States because the accompanying brain injury is hard to undo or work around.

"It's a huge problem," Andreasson told me. The best treatments available now, clot-busting drug infusions and clot-removing surgery, are useful only for a fraction of those who experience strokes -- and in many cases only if these interventions are done within the first several hours afterward -- she said.

Again, from my release:

The great majority of strokes occur because a clot lodges in a blood vessel supplying the brain with oxygen and other nutrients. The sudden oxygen cutoff damages the brain tissue dependent on that blood vessel. Once circulation resumes, inflammation-generating breakdown products of dead or dying cells are carried off from the injured brain to distant sites in the body, drawing the attention of immune 'first responders' called myeloid cells that reside mainly in the spleen -- effectively a barracks for immune cells -- and bloodstream. The brain junk jams many of those myeloid cells into inflammatory gear, inducing them to migrate to the brain in search of trouble. .... Inflammation in the brain persists for several days after a stroke, further damaging tissue and compounding patients' loss of function.

But here's the good news: Myeloid cells uniquely feature, on their surfaces, a molecule that acts as an inflammatory loudspeaker. Turning down its volume softens the inflammatory disposition of the immune cells. Andreasson's team learned of an experimental drug that seems to be able to do that -- and it worked, at least in mice.

The next step, of course, is to get it into people who've had strokes and see if it works for us humans, too.

Photo by Kristina Flour

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