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Stroke. 2007 Aug;38(8):2329-36. Epub 2007 Jun 28.

Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia.

Author information

1
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

BACKGROUND AND PURPOSE:

Leptin is the major adipose hormone that regulates body weight and energy expenditure by activating leptin receptors in the hypothalamus. Leptin receptors are also present in other cell types, and a potent antiapoptotic effect for leptin has recently been reported. We investigated whether leptin was neuroprotective against ischemic brain injury.

METHODS:

In vitro ischemic injury was induced in rat primary neuronal culture by oxygen-glucose deprivation for 90 minutes. In vivo ischemic brain injury was induced by middle cerebral artery occlusion in mice for 60 minutes.

RESULTS:

Leptin receptors were detected in cultured rat cortical neurons, as well as in the mouse cortex, striatum, and hippocampus. In vitro results showed that leptin, 50 to 100 mug/mL, protected primary cortical neurons against death induced by oxygen-glucose deprivation in a concentration-dependent manner. In vivo studies in the mouse brain demonstrated that the intraperitoneal administration of leptin, 2 to 8 mg/kg, dose-dependently reduced infarct volume induced by middle cerebral artery occlusion. Leptin was effective when injected 5 minutes before or 30 to 90 minutes after reperfusion, but not 2 hours after reperfusion. Leptin improved animal body weight recovery and behavioral parameters after cerebral ischemia. Leptin enhanced the phosphorylation of extracellular signal-related kinase 1/2. Both extracellular signal-related kinase 1/2 activation and neuroprotection were abolished by the administration of PD98059 in vitro and in vivo.

CONCLUSIONS:

Leptin is neuroprotective against ischemic neuronal injury. Our findings suggest that leptin is a legitimate candidate for the treatment of ischemic stroke.

PMID:
17600230
DOI:
10.1161/STROKEAHA.107.482786
[Indexed for MEDLINE]

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