P4‐096: Picalm Mediates Autophagic Abeta Clearance and Toxicity Mitigation in Pericytes

injury was investigated by modulation of brain O-GlcNAcylation level pharmacologically and with a molecular approach before induction of MCAO. Results:We found an initial large elevation (1-4 hours after ischemia) and then marked decline of protein O-GlcNAcylation during cerebral ischemia. If reperfusion occurred two hours after ischemia, the elevation of O-GlcNAcylation lasted longer. The transient elevation of brain O-GlcNAcylation during the early phase of ischemia was neuroprotective and helped ameliorate cerebral ischemia-reperfusion injury. Interference of the transient elevation of O-GlcNAcylation aggravated the ischemiainduced brain damage, motor deficits and mortality. Conclusions: This study reveals a novel regulation of cerebral ischemia-reperfusion injury by O-GlcNAcylation and also provides a possible new therapeutic strategy, i.e., to reduce the cerebral damage and improve the clinical outcome of ischemic stroke and dementia associated with cerebral ischemia by increasing O-GlcNAcylation.