Abstract 55: Interleukin 4 Improves White Matter Repair After Stroke By Promoting Oligodendrocyte Differentiation

• DOI: 10.1161/str.50.suppl_1.55
• Publication Date: 2019-01-30T09:26:49Z
• Authors: Qingxiu Zhang; Wen Zhu; Fang Yu; Yanqin Gao; Jun Chen; Xiaoming Hu
• Keywords: Stroke; Knockout mouse

Introduction: White matter (WM) injury is an important cause of long-term deficits after stroke. This study explores a novel action IL-4 on promoting WM integrity stroke and elucidates the underlying mechanisms. Hypothesis: promotes repair enhances neurological recovery ischemic by targeting both OPC differentiation microglial polarization. Methods: Cerebral ischemia was induced transient (60 min) middle cerebral artery occlusion (tMCAO) in wild type, knockout oligodendrocyte precursor cell (OPC)-specific PPARγ KO mice. The animals were then randomly assigned to vehicle or treatment. delivered intranasally 6h repeated every day at 1-7d, 14d, 21d, 28d tMCAO. Sensorimotor determined adhesive removal, rotarod test corner test. Cognitive water maze A combined approach including cell-specific depletion, immunohistology staining, electron microscopy (EM), diffusion tensor imaging (DTI) electrophysiology, applied evaluate integrity. Results: (KO) mice exhibited worse sensorimotor deteriorated over 14 days In contrast, intraventricular infusion beginning MCAO attenuated cognitive improved integrity, as revealed EM, DTI electrophysiology. addition microglia/macrophage M2 polarization, treatment enhanced brain organotypic cultures. Interestingly, IL-4-afforded oligodendrogenesis still potent microglia depleted (with PLX5662) vitro confirmed that directly primary OPCs into mature oligodendrocytes. effect mediated through activation PPARγ. therapeutic efficacy white protection significantly reduced OPC-specific Conclusions: PPARγ-dependent manner. may represent recovery-enhancing strategy promote functional