Apelin-13/APJ promotes neural stem cells to repair ischemic stroke

Neural stem cell therapy is considered as a promising new therapy for ischemic stroke. However, the therapeutic efficacy of neural stem cells (NSCs) is hampered by the effects of cerebral ischemia and hypoxia, resulting in suboptimal performance. Drug stimulation can further improve the efficacy of NSCs in ischemic stroke, among which the small molecule peptide Apelin-13 could have the potential. In this study, we simulated the ischemic anoxic microenvironment by oxygen-glucose deprivation (OGD) to observe the improvement of Apelin-13 on NSCs treatment-related functions. Six hours of OGD treatment suppressed the cell viability of NSCs, while 100 nM Apelin-13 mitigated this suppression. Additionally, OGD treatment reduced the migration capability of NSCs, but Apelin-13 enhanced this ability under OGD conditions. OGD also increased the rate of apoptotic NSCs and decreased the ratio of Bcl-2 to Bax. In the OGD environment, BDNF expression was elevated, and Apelin-13 further increased this level. APJ is the endogenous receptor of Apelin-13. We knocked down the expression of APJ and observed that the effect of Apelin-13 on NSCs was abolished in the OGD environment compared with the negative control group with knockdown, and the upregulation of the expression of brain derived neurotrophic factor (BDNF) was also lost. Our study found that Apelin-13 enhances the cell viability of NSCs, fosters cell migration, diminishes apoptosis, and augments the expression of BDNF under conditions of OGD through the APJ receptor. The stimulation of the Apelin-13/APJ system may play a beneficial role in activating endogenous NSCs for the purpose of treating ischemic stroke. This positive effect may be mediated by the downstream effector protein, BDNF.