Apelin-13 Inhibits Apoptosis of Cortical Neurons Following Brain Ischemic Reperfusion Injury in a Transient Model of Focal Cerebral Ischemia

作者：Aboutaleb Nahid; Kalalianmoghaddam Hamid; Eftekhari Sanaz; Shahbazi Ali; Abbaspour Hadi; Khaksari Mehdi^*

来源：International Journal of Peptide Research and Therapeutics, 2014, 20(2): 127-132.

DOI：10.1007/s10989-013-9374-8

• Apelin-13
• Apoptosis
• Transient focal cerebral ischemia
• Rat

Stroke is the third leading cause of death world-wide, affecting 15 million people annually. Diminished blood supply to the brain cells is the main cause of damage following stroke. When focal ischemia occurs, the core of brain tissue influenced by reduced blood supply undergoes necrotic cell death. 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 and apoptosis. In addition, this peptide has neuroprotective effect on hippocampal and cultured mouse cortical neurons against NMDA receptor-mediated excitotoxicity as well as cortical neurons from ischemic injury. The present study was conducted to determine whether Apelin-13 inhibits apoptosis in the ischemic penumbra in transient focal cerebral ischemia. Focal cerebral ischemia was induced in male Wistar rats by 60 min middle cerebral artery occlusion (MCAO) using a filament method, followed by 23-h reperfusion. Saline as a vehicle and Apelin-13 at doses of 50 and 100 mu g were injected intracerebro-ventriculary (ICV) at the beginning of ischemia. Apoptosis and neurological dysfunction were assessed 24-h after MCAO. Our results indicated that administration of Apelin-13 at doses of 50 and 100 mu g ICV markedly reduced apoptosis by decreasing positive TUNEL cells (P < 0.001). In addition, Apelin-13 at doses of 100 mu g significantly change neurological dysP < 0.05). Our findings demonstrate that treatment by Apelin-13 exerts its protective effects in ischemic models via blocking programmed cell-death. We suggest that Apelin-13 might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of Apelin-13 in stroke patients.

• 出版日期2014-6