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 μg 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 μg ICV markedly reduced total infarct volumes by 45 and 55 %, respectively (P < 0.001), but injection of apelin at lower dose (25 μg) did not change infarct volume significantly (P > 0.05). In addition, apelin-13 at doses of 50 and 100 μg 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).
Physiology Research Center and Physiology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mehdi
M
Khaksari
Nahid
N
Aboutaleb
Farinaz
F
Nasirinezhad
Abedin
A
Vakili
Zahra
Z
Madjd
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C495199:apelin-13 peptide; C505410:Casp3 protein, rat; D053148:Caspase 3