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Can immune cells’ anomalous presence in brain explain delayed post-stroke dementia?

bees in the bonnetAbout every 40 seconds, someone in the United States has a stroke. About one in three of those people will eventually suffer from dementia if they live long enough, even if there's been no initial damage to brain structures involved in memory and cognition. That's a mystery.

In a recent study in The Journal of Neuroscience, Stanford neurologist and stroke expert Marion Buckwalter, MD, PhD, points a bony scientific finger at a major likely reason why having a stroke doubles a person's risk of incurring dementia within the next decade.

The culprit, surprisingly, seems to be a type of normally very beneficial immune cells that under ordinary circumstances have no business being in the brain. These trespassers, called B cells, are best known for generating antibodies that fight off invading pathogens. As I wrote in my release on the new study:

The antibodies that B cells produce are normally of great value to us. They circulate throughout blood and lymph, and bind to microbial invaders, gumming up the pathogens' nefarious schemes and marking them for destruction by other immune cells. Occasionally, B cells wrongly begin generating antibodies that bind to the body's own healthy tissues, causing certain forms of autoimmune disease, such as rheumatoid arthritis. Rituxan, a drug approved by the Food and Drug Administration for this condition, is actually an antibody itself: Its target is a protein found on the surface of every B cell. Use of this drug depletes B cells in the body, relieving the symptoms of rheumatoid arthritis and other B-cell-mediated disorders.

The blood-brain barrier, which tightly controls what enters and what leaves the brain, can be disrupted by a stroke, permitting the anomalous appearance of B cells there. Buckwalter and her colleagues showed that in mice experiencing strokes, the affected brain region - immune-cell-free at least one week later - started filling up with B cells until, at seven and twelve weeks post-stroke, there were "tons" of them, she told me. Around the same time, these mice started showing signs of dementia that hadn't been at all evident a mere week after the stroke.

But in mice of a strain that is genetically incapable of producing B cells, no such cognitive loss occurred. Not only that, but giving plain old ordinary mice Rituxan five days after a stroke prevented this post-stroke dementia.

Then Buckwalter and her team looked at preserved, autopsied brain-tissue samples from people who had had stroke and dementia. Once again, they observed inordinate numbers of B cells in the majority of these brains, suggesting that humans, too, can experience late but lasting infiltration of rampaging B cells into our brains after a stroke.

So maybe giving a Rituxan-like B-cell-depleting compound to these people within that first week after their stroke could stave off dementia.

This wouldn't by advisable for all stroke patients. You don't want to wipe out somebody's B cells (usually, they're good guys) unless they are causing trouble. And, as seen in the autopsied tissue samples, not all stroke sufferers' brains fall into that category.

But, Buckingham noted, Rituxan or something like it could work a double shift as both a therapeutic and a diagnostic. Rituxan pretty much binds only to B cells (a prelude to killing them), so tagging the drug with an imaging agent that could be picked up by, say, an MRI scan might tell clinicians which stroke patients have, or don't have, B's in their bonnets.

Previously: Targeted stimulation of specific brains cells boosts stroke recovery in mice, Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed and Brain sponge: Stroke treatment may extend time to prevent brain damage
Photo by _annamo

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