Researchers at Weill Cornell Medicine have revealed that stroke induces widespread shifts in gene activity within the brain’s tiny blood vessels, offering potential targets for future therapies aimed at mitigating stroke damage. The findings appear in the Proceedings of the National Academy of Sciences.
Most strokes are ischemic, caused by a blockage that interrupts blood flow in cerebral vessels. This interruption sets off inflammatory cascades that can harm small vessels as well, contributing to brain injury after a stroke. Capturing these microvascular changes had been technically difficult, which limited understanding of their role in stroke outcomes.
By applying advanced methods, the team tracked post-stroke changes in gene expression specifically within brain microvessels in mice and confirmed that some of these changes were also present in human microvessels from stroke patients. Overall, the study identified 541 genes whose activity shifted after stroke in both mouse and human brain microvessels.
A substantial portion of these genes connects to conditions such as encephalitis, vascular disease, and forms of vascular dysfunction that can cause leaks in the brain’s tiny vessels. Leaky microvessels reflect a compromised blood-brain barrier, a critical guard that normally limits which components of circulating blood can enter brain tissue.
Several molecules highlighted by the study are already being explored as targets for other diseases. The researchers’ work opens the possibility of repurposing existing drugs for stroke treatment and points to new directions for developing medicines that address microvascular inflammation and barrier integrity after stroke. These insights pave the way for therapies that could protect brain tissue by stabilizing microvessels and reducing secondary injury in the days and weeks following a stroke. (Weill Cornell Medicine study; PNAS, referenced in related scientific discussions)