TY - EJOU AU - LI, Zheng AU - ZHAO, Zhongle AU - ZHANG, Peng TI - Nerve growth factor alleviates cerebral infarction and neurologic deficits by regulating VEGF, SDF-1 and S100A12 expression through PI3K pathway T2 - BIOCELL PY - 2019 VL - 43 IS - 3 SN - 1667-5746 AB - Stroke remains the leading cause of death and disability worldwide, which destroys the quality of patients’ lives and thus is becoming a heavy burden to the society. However, the current therapeutic approaches are far from satisfaction. The objective of this study is to elucidate the impact of nerve growth factor (NGF) on the brain damage induced by cerebral ischemia and its potential molecular mechanism. Middle cerebral artery occlusion (MCAO) rats were used as animal models and neurological functions were evaluated by modified Neurological Severity Score (NSS). Brain cell apoptosis was analyzed by TUNEL-positive staining while brain infarct size was determined according to 2% 2,3,5-triphenyltetrazolium chloride (TCC) staining volume. Rats receiving NGF demonstrated significantly alleviated brain damage, reflected by a substantial improvement in the neurobehavioral outcome, a decrease in brain cell apoptosis and shrinkage of brain infarct volume. Further analysis revealed a markedly elevated circulating vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) levels as well as a significant downregulation of SA10012 expression in NGF treated group compared with the untreated group. Strikingly, the protective effect of NGF on cerebral ischemic injury was abolished in rats treated with both NGF and PI3K inhibitors, indicating that phosphoinositide-3-kinase (PI3K) signaling is essential for NGF function. In conclusion, NGF treatment might be a potential therapeutic approach against cerebral infarction by downregulating SA10012 expression and upregulating VEGF, SDF-1 in a PI3K signaling dependent manner. KW - Cerebral infarction KW - Nerve growth factor KW - PI3K KW - SA10012 KW - SDF-1 KW - VEGF DO - 10.32604/biocell.2019.06922