Perlecan Regulates Pericyte Dynamics In The Repair Process Of The Blood-Brain Barrier Against Ischemic Stroke

Introduction: The blood-brain barrier (BBB) breakdown occurs when the integrity of BBB components is lost as a consequence of ischemic stroke. Perlecan, a major heparan sulfate proteoglycan of basement membranes, is expressed by endothelial cells (ECs) and is adjacent to pericytes (PCs), suggesting supportive functions in the BBB. Recent studies highlight the importance of PCs in the process of repairing BBB functions, which are triggered by the upregulation of platelet-derived growth factor receptor β (PDGFRβ). We hypothesized that perlecan may play a protective role in BBB maintenance through the interaction with PCs during the repair process of the BBB disruption. Methods: We induced a 60-minute middle cerebral artery occlusion (MCAO) in adult conditional perlecan-deficient (Perlecan-/--Tg) mice in a C57BL/6 background, which express the perlecan transgene only in cartilage to rescue the perinatal lethality of Perlecan-/- mice. Recombinant perlecan C-terminal domain V (DV) was used for in vitro assays....