Leptin administration alleviates ischemic brain injury in mice by reducing oxidative stress and subsequent neuronal apoptosis

BACKGROUND: Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model. METHODS: The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/lewkmia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay. RESULTS: Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury. CONCLUSIONS: Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.