Interleukin 4 Improves White Matter Repair After Stroke By Promoting Oligodendrocyte Differentiation

Introduction: White matter (WM) injury is an important cause of long-term deficits after stroke. This study explores a novel action of IL-4 on promoting WM integrity after stroke and elucidates the underlying mechanisms. Hypothesis: IL-4 promotes WM repair and enhances long-term neurological recovery after ischemic stroke by targeting both OPC differentiation and microglial polarization. Methods: Cerebral ischemia was induced by transient (60 min) middle cerebral artery occlusion (tMCAO) in wild type, IL-4 knockout and oligodendrocyte precursor cell (OPC)-specific PPARγ KO mice. The animals were then randomly assigned to vehicle or IL-4 treatment. IL-4 was delivered intranasally 6h after stroke and repeated every day at 1-7d, 14d, 21d, and 28d after tMCAO. Sensorimotor deficits were determined by adhesive removal, rotarod test and corner test. Cognitive deficits were determined by water maze test. A combined approach including cell-specific depletion, immunohistology staining, electron microscopy (EM), di...