Effects of brain-derived neurotrophic factor pretreatment on oxidative stress and neuron apoptosis following focal cerebral ischemia-reperfusion injury in rats

Objective To investigate the effects of different dose of brain-derived neurotrophic factor (BDNF) pretreatment on oxidative stress and neuron apoptosis following focal cerebral ischemia-reperfusion injuries in rats. Methods Focal cerebral ischemia-reperfusion model was established in rats by reversible left middle cerebral artery occlusion with filament. Left cerebral ischemia was for 2 hours and then with 72 hours reperfusion. BDNF was injected into the lateral ventricle before ischemia for 12 hours. The activities of brain tissue superoxide dismutase (SOD) were measured by the method of xanthine oxidase and the contents of brain tissue malondialdehyde (MDA) were determined by the method of thiobarbituric acid. Neuron apoptosis was identified by TUNEL and immunohischemistry was used to detect the expression of Bci-2 and Bax protein in cerebral cortex. Results Compared with group I/R, the activity of SOD was increased significantly but the content of MDA was decreased significantly in ischemia brain tissue in every BDNF pretreatment group( P<0.05 or P <0.01 ). The index of apoptotic neuron cells and the expression of Bax protein positive cells in BDNF pretreatment groups were decreased significantly ( P <0.01) while the expression of Bcl-2 protein positive cells was increased significantly ( P <0. 01 ) in ischemia brain cortex. In high dose of BDNF pretreatment group, the SOD activity and the expression of Bcl-2 protein were the highest but the content of MDA and the expression of Bax protein and the index of apoptotic neuron ceils were the lowest( P <0. 05 or P <0. 01 ). Conclusions Different dose of BDNF pretreatment could significantly reduce the oxidative stress and neuron apoptosis following focal cerebral ischemia-reperfusion, which has varying degree cerebral protection. The protection may be related to the dose of BDNF pretreatment. The mechanism of protection may be related that BDNF pretreatment can increase the content of endogenous anti- oxidation agents and regulate the different expression of apoptosis-related gene. Key words: Brain-derived neurotrolahic factor/PD; Brain ischemia/Bl; Reperfusion injury; Oxidative stress; Apoptosis; Neuron