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How inflammation and blood flow patterns clog small brain vessels after stroke treatment
When someone has an ischemic stroke, a clot blocks blood flow to part of the brain. Doctors can now remove the main clot in nearly all eligible patients using a procedure called thrombectomy. Yet up to half of these patients still don't recover well, because blood flow fails to fully return to the smallest vessels. This problem is known as "no reflow." We studied why this happens. Using live imaging of the brain in mice, computer modeling of blood flow, and blood samples from stroke patients, we found that two forces combine to clog these tiny vessels. First, after the clot is removed, blood begins flowing in new, converging directions that physically stretch and switch on a sticky blood protein called von Willebrand factor (VWF), which then traps platelets. Second, an inflammatory signal called IL-6, released during the acute phase of stroke, blocks the body's natural enzyme (ADAMTS13) that normally cuts VWF back down to size. Together these create ideal conditions for new microscopic clots. In patients, higher IL-6 tracked with higher VWF activity, and the highest VWF activity appeared in those with the worst outcomes. Blocking VWF, blocking IL-6, or restoring the cutting enzyme in mice all improved blood flow.
