OPCs are known to respond early and robustly to white matter ischemic lesions common to the aging human brain.31,49,50 The peri-infarct white matter at the margin of the ischemic lesion, often referred to as the white matter penumbral region,51 is where reparative remyelination can be activated.31 In DIO mice, the stroke-responsive OPC lesion area is 30% larger, and this expanded penumbral region is marked by increased endothelial CXCL5 expression, potentially explaining why more stroke-responsive OPCs are seen at the lesion periphery. The gene discussed is CXCL5; the disease is Stroke.