Effects of different interval intracerebroventricular administration of brain-derived neurotrophic factor on oxidative stress and neuron apoptosis following cerebral ischemia-reperfusion injury in rats
AIM: To compare the effects of different interval intracerebroventricular administration of exogenous brain-derived neurotrophic factor(BDNF) on oxidative stress and neuron apoptosis following cerebral ischemia-reperfusion(I/R) injury in rats. METHODS: Focal cerebral I/R model were established in rats by reversible left middle cerebral artery occlusion with filament. Left cerebral ischemia was for 2 h and then with 24 h reperfusion. BDNF (0.5 μg) was microinjected intracerebroventricularly at 12, 6 h before ischemia and at 0, 6, 12 h after I/R. The activitiy 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 in brain cortex was identified by TUNEL. One left brain cortex (1 mm × 1 mm) was removed randomly in each group to observe the change of ultrastructure of cerebral tissue with transmission electron microscopy. RESULTS: Compared with group I/R, the activity of SOD was significantly increased but the content of MDA was significantly decreased in ischemia brain tissue in every BDNF treatment group. While in brain cortex the index of apoptotic neuron cells in BDNF treatment groups was significantly decreased(P ＜ 0.05 or P ＜ 0.01). The activity of brain tissue SOD was higher and the content of MDA and the index of neuron apoptosis were lower in the BDNF treatment group at 12, 6 h before ischemia(P ＜ 0.05 or P ＜ 0.01). Transmission electron microscopy showed that the neurons chromatin of the brain cortex of the ischemic hemisphere condensated, agglomerated or marginated and part of disintegrated, the cytoplasm became swelling and expansion, the mitochondrion became swelling and the mitochondrial cristae fragmented or disappeared. Part of apoptotic cell splited into small fragments and part of the nucleus and cytoplasm were encapsulated with membrane structure to form characteristic of apoptotic bodies. But the injury of the neuron ultrastructure in the brain cortex of the ischemic hemisphere was mild or little in every BDNF treatment group, the cytoplasm was relatively more homogeneous, the chromatin was mild agglomeration and the nucleolus was existent, The structure of the mitochondrion was almost normal or little change. CONCLUSION: Different interval intracerebroventricular administration of exogenous BDNF could significantly reduce the oxidative stress and neuron apoptosis following focal cerebral I/R in rate, has obvious protective effect on brain injury. The better effect of BDNF treatment is microinjected intracerebroventricularly before ischemia.
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NSTL
万方数据
维普
