Intranasal administration of nerve growth factor promotes angiogenesis via activation of PI3K/Akt signaling following cerebral infarction in rats

Angiogenesis plays a critical role in neural repair following ischemic stroke. Therapeutic angiogenesis contributes to neurological functional recovery after cerebral infarction. Nerve growth factor (NGF) has been reported as a neurotrophic factor. However, the angiogenic efficacy of NGF in cerebral ischemia remains unclear. In this study, we investigated the effect of NGF on angiogenesis in the ischemic penumbra and neurological outcome in a rat model of middle cerebral artery occlusion (MCAO). Our results demonstrate that the intranasal administration of NGF improves neurological outcome and reduces infarct volume on day 7 after MCAO in rats. Treatment with NGF promoted angiogenesis in the peri-infarct region, increased the serum levels of VEGF and SDF-1 protein, and elevated the number of circulating endothelial progenitor cells (EPCs) on day 4 after MCAO. In addition, NGF enhanced capillary-like tube formation of rat brain microvascular endothelial cells in vitro, further confirming its angiogenic effect. Furthermore, the neuroprotective and angiogenic effects of NGF can be significantly attenuated by the phosphatidylinositide 3-kinase (PI3K)/Akt pathway antagonist LY294002. Our results indicate that NGF-enhanced angiogenesis contributes to neurological functional recovery after ischemic stroke, which may occur partly via activation of the PI3K/Akt signaling pathway. This study provides novel experimental evidence for the angiogenic role of NGF in treating ischemic stroke.