Abstract TP246: The Role Of Pericytes In Ischemic Stroke

Abstract

Stroke is one of the leading causes of death worldwide. Loss of blood flow, typically from a blood clot that occludes the cerebral vasculature, causes ischemia, tissue death, and long-term cognitive deficits. Following stroke, the blood-brain barrier (BBB) is damaged, causing leakage of ions, molecules, toxins, and immune cells into the brain. Pericytes are a perivascular cell that is important for neurovascular growth and stability, and have been reported to both aid vascular regrowth and transdifferentiate into pro-inflammatory cells after ischemic injury. However, markers used to identify pericytes non-specifically label other cell types, making it unclear whether these studies are specifically identifying pericytes. In order to understand how pericytes adapt to ischemic injury, we modeled stroke in mice with distal middle cerebral artery occlusion (dMCAO) and lineage traced these cells with two novel pericyte markers: TBX18 and Atp13a5, allowing us to track ischemia-induced changes in pericytes and their progeny. We discovered that pericytes in the ischemic core die over the first three days following injury, while surviving pericytes proliferate in response to injury, and investigated how pericyte identity changes with histology and single cell RNA sequencing.