Cerebral ischemia-reperfusion (I/R) injury is a major problem worldwide. The Notch signaling pathway plays an important role in\nneural progenitor cell differentiation and in the inflammatory response after central nervous system injury.This study evaluated\nwhether the neuroprotective effect of cerebral ischemic preconditioning (cIPC) is mediated by the preactivation of the Notch\nsignaling pathway. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model and glucose deprivation/reoxygenation\n(OGD/R) cell model were constructed to detect the neuroprotective effects of cIPC. In in vivo experiments, cIPC reduces the\nneurological functional deficit, cerebral infarction, and cellular apoptosis in the hippocampus induced by middle cerebral artery\nocclusion/reperfusion (MCAO/R), thus indicating that cIPC can improve neurologic function. Moreover, cIPC can reveal the\nexpression peak of Jagged1,Notch1,NICD, andHes1 protein, thereby indicating that cIPCcanpreactivateNotch signaling.However,\ncIPC-induced improvements in neurologic function are compromised by the .. secretase inhibitor N-(N-(3,5-difluorophenacetyl)-\n1-alanyl)-S-phenylglycine t-butyl ester (DAPT). In in vitro experiments, OGD preconditioning (OGDPC) can clearly upregulate\nNotch1 expression in the OGD/R-treated neuron and neural stem cell. Notch1 pre-overexpression can decrease neuron death and\napoptosis under OGD/R treatment. Notch1 pre-overexpression can decrease the percentage of G1 stage cells and increase the\npercentage of S stage cells in OGD/R-treated neural stem cell. Furthermore, Notch1 pre-knockdown has the opposite effect on\ncell survival, apoptosis, and cycle in both OGD/R-treated neuron and neural stemcell. In conclusion, our results demonstrate that\nthe neuroprotective effects of cIPC in a ratMCAO/R model are mediated by the preactivation of the Notch signaling pathway.
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