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Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2011 Dec 05; Vol. 671 (1-3), pp. 61-9. Date of Electronic Publication: 2011 Sep 28. - Publication Year :
- 2011
-
Abstract
- 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 (1mg/kg in 200 μL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 μg/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 × 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.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Brain blood supply
Brain drug effects
Brain pathology
Brain physiopathology
Calcitonin Gene-Related Peptide antagonists & inhibitors
Caspase 3 genetics
Cell Hypoxia drug effects
Cerebrovascular Circulation drug effects
Leptin therapeutic use
Male
Mice
Nervous System Diseases complications
Nervous System Diseases drug therapy
Neurons drug effects
Neurons metabolism
Neurons pathology
Neuroprotective Agents therapeutic use
Oxygen metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Regional Blood Flow drug effects
Reperfusion Injury pathology
Reperfusion Injury physiopathology
Up-Regulation drug effects
Brain Ischemia complications
Calcitonin Gene-Related Peptide genetics
Gene Expression Regulation drug effects
Leptin pharmacology
Neuroprotective Agents pharmacology
Reperfusion Injury drug therapy
Reperfusion Injury genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 671
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21968137
- Full Text :
- https://doi.org/10.1016/j.ejphar.2011.09.170