Targeting Inflammation May Protect and Restore the Brain after Stroke

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An additional benefit of B4Crry is that it appears to stick around for only a few days, allowing the brain pick up its own protective mechanisms later on, Alawieh says. “That’s a big advantage,” he adds, “because we’re not depleting the brain of the immune component that it may need during recovery.”

Neurologist Alastair Buchan at the University of Oxford, who was not involved in the new study, says this is very intriguing approach. But he cautions that pinpointing exactly when and where to administer such a treatment in humans would be more difficult than it is in mice. Tissue in the human post-stroke brain may recover at different rates and therefore may not benefit from complement inhibition at the same time, Buchan explains.

Tomlinson—who co-founded Admirx, a company developing complement inhibitors for stroke and other disorders—is currently trying to make his team’s antibody compatible with humans so the experimental compound can proceed to clinical trials.

Downstream Effects

Even after acute stroke treatment continuing inflammation can damage the brain and impair behavior, potentially contributing to progressive cognitive decline. “It was only recently discovered that cognitive impairment after stroke occurs in a progressive fashion,” Fagan says. “We use to think it was stepwise, that cognition would decline [each time] you had another stroke.”

To address these long-term problems, some researchers are looking to target the inflammatory response days, weeks and even months after a stroke. The challenge, however, is that the role the immune response plays during these time periods is still unclear. Whereas brain inflammation is harmful when it occurs immediately after stroke, parts of the immune response that are activated later seem beneficial for recovery, says Arthur Liesz, a neurologist at Ludwig Maximilian University in Germany. “How different immune components behave in the chronic phase is still unknown,” he adds.

Indeed, some research hints that promoting the activity of certain immune-response components during this later phase could aid in recovery after a stroke. New findings, reported last month in Science Advances by neuropharmacologist Mikko Airavaara at the University of Helsinki and his colleagues, suggest increasing the presence of debris-gobbling cells a few days after stroke may have beneficial effects.

Airavaara and his team injected a neurotrophic factor (a type of molecule that helps neurons grow and survive) into the peri-infarct region—the brain tissue surrounding the site of a stroke—in rats. When this procedure was carried out a few days after an induced stroke, the animals exhibited some improvements in behavior. Further analysis pointed to a potential explanation: An increase in the expression of genes found in immune cells that consume debris indicated this cellular cleanup crew might be facilitating repair in the peri-infarct area. This work is still in the early stages, and Airavaara notes more research is needed to determine whether their compounds can help humans.

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