Potential targets for protecting against hippocampal cell apoptosis and cognitive function after transient cerebral ischemia in aged rats

Objective To investigate the effect of transient cerebral ischemia-reperfusion injury on cognitive function and cell apoptosis in the hippocampus of aged rats.In addition, to further study it's mechanism. Methods 40 old healthy Wistar rats were randomly divided into the control group(n= 20)and ischemia group(n= 20).The global cerebral ischemia model was produced by four-vossel occlusion as described by Pusinelli.On days 2-7 after model establishment, rats were behaviorally assessed in a Morris water maze.After the behavioral tests were completed, ten rats in each group were randomly selected to be purfused from heart and to be fixed. Then the brain was taken to be maken into paraffin section.The neurones apoptosis in hippocampus was detected by Td T-mediated d UTP nick end labeling(TUNEL) method. The remained 10 rats in every group were decapitated and the hippocampus were separated on ice.After mitochondria were extracted and purified, the differences of proteins expression between two group were analyzed by two dimensional polyacryalmide gel electrophoresis and ultraflex TOF/TOF mass spectrograph. The original data were preprocessed by Mascot Distillerthen searched in NCBI nr database. Results Morris water maze test results showed that the cognitive function of aged rats with transient cerebral ischemia was declined compared with that of control rats。TUNEL staining showed that the number of apoptotic cells was significantly increased in the ischemia group, The number of apoptotic cells counted in high-power fields was 3. 21±3. 76 and 20. 50±5. 83 in the control and ischemia groups, respectively, and these counts were significantly different(P< 0. 01).Compare with the control group, the ischemia group gained 10 different protein spots, 7 spots expressed highly, and 3 spots expressed lowly. 10 protein were identified through these spots. Conclusion The aging rats were much more sensitive to ischemia-reperfusion injury.The number of TUNEL-positive cells raised significiently, and cognitive dysfunction only after transient cerebral ischemia.Cerebebral ischemia affects the proteins related to hippocampal mitochondria, which suggests that these proteins may be correlated with the energy metabolism and apoptosis of mitochondria. Key words: Cerebral ischemia; Ischemia-reperfusion injury; Hippocampus; Cognitive function; Apoptosis; Mitochondria; Comparative proteomics