Abstract DP197: Blockade of VCAM1 or VLA4 promotes normal cerebrovasculature and prevents cognitive decline late after stroke

Introduction: Infarct-induced neurodegeneration occurs chronically after stroke, doubling the risk of dementia. Vascular cell adhesion molecule 1 (VCAM1) facilitates blood-brain barrier (BBB) opening and immune cell diapedesis by binding very late antigen 4 (VLA4). We hypothesized that elevated VCAM1 persists after stroke and contributes to vascular dysfunction and cognitive decline. Methods: VCAM1 was measured in plasma from 106 humans with chronic stroke (median 10 mo) and 212 healthy controls matched for age, sex, and sample storage time using two SomaLogic aptamers. Adult (3 mo) and middle-aged (10 mo) C57BL/6J male&female mice (N=9-10/group) underwent permanent middle cerebral artery occlusion and were dosed with anti-VCAM1, anti-VLA4 or isotype control every 3 days beginning 4 days after stroke. Barnes maze and novel object were performed at -1, 1 and 6 weeks, and scRNASeq was performed on immune and endothelial cells at 10 weeks. We quantified vessel length, pericyte (CD13) coverage of vasculature (CD31), tight junctions (ZO-1), and extravascular fibrinogen with immunostaining. Results: VCAM1 was elevated in plasma of humans with chronic stroke by 10-13% (p