Apelin-13 Protects the Brain Against Ischemic Reperfusion Injury and Cerebral Edema in a Transient Model of Focal Cerebral Ischemia

The adipocytokine apelin is a peptide that was isolated from a bovine stomach for the first time. This peptide and its receptor are abundantly expressed in the nervous and cardiovascular systems. According to previous studies, apelin-13 protects cardiomyocytes from ischemic injury as well as apoptosis. In addition, this peptide has a neuroprotective effect on hippocampal and cultured mouse cortical neurons against NMDA receptor-mediated excitotoxicity. The present study was conducted to determine whether apelin-13 provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and apelin-13 at doses of 25, 50, and 100 mu g were injected intracerebroventriculary (ICV) at the beginning of ischemia. Infarct volume ,brain edema, motor dysfunction, and apoptosis were assessed 24 h after MCAO. Treatment with apelin-13 at doses of 50 and 100 mu g ICV markedly reduced total infarct volumes by 45 and 55 %, respectively (P < 0.001), but injection of apelin at lower dose (25 mu g) did not change infarct volume significantly (P > 0.05). In addition, apelin-13 at doses of 50 and 100 mu g reduced brain edema (P < 0.001) and inhibited apoptosis by decreasing caspase-3 activation (P < 0.001). Apelin-13 did not significantly change neurological dysfunction (P > 0.05).