Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 671, Issue 1-3, Pages 61-69Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2011.09.170
Keywords
Leptin; Calcitonin gene-related peptide; CGRP(8-37); Cerebral ischemia/reperfusion; Hypoxia/reoxygenation; Neuroprotection
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Funding
- National Natural Science Foundation of China [30670821]
- National Key Technology RD Program [2006BAF07B01]
- Chinese PLA General Hospital [06MP83]
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Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1 mg/kg in 200 mu L normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 mu g/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37) (4 x 10(-8) mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression. (C) 2011 Elsevier B.V. All rights reserved.
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