Effect of methazolamide on cognitive function in spontaneous subarachnoid hemorrhage mice

Objective To investigate the effect and mechanism of methazolamide on cognitive function in spontaneous subarachnoid hemorrhagic (SAH) mice.Methods Ninety male adult C57BL/6J mice were randomly divided into 3 groups:sham group,SAH + vehicle group,and SAH + methazolamide group.SAH model was established by endovascular puncture method,and the blood flow of bleeding cerebral hemisphere was measured by laser Doppler flowmeter.The neurological appraisal and cognitive function were evaluated by Open-field test.The apoptosis of neurons in the hippocampus of the bleeding cerebral hemisphere was examined by using TdT-mediated dUTP nick end labeling (TUNEL) staining.Immunochemistry was used to evaluate the expression level of Caspase-3 in the hippocampus after SAH.Results SAH total mortality was 25.3％.Mortality showed no statistically significant difference between SAH + vehicle group (26.1％) and SAH + methazolamide groups (24.4％).The total distance and Centre time in SAH + methazolamide group at 3rd,7th,and 14th day were significantly increased as compared with SAH + vehicle group at the same time points (P ＜ 0.05).Although the MCA diameter in the sham group (106.89 ± 8.66) was larger than in SAH + vehicle group (87.11 ± 6.73) and SAH + methazolamide group (89.39 ± 7.22,P ＜ 0.05),there was no significant difference between SAH + vehicle group and SAH + methazolamide group (P ＞ 0.05).The TUNEL positive cells rate in the hippocampus in SAH + methazolamide group was lower than in SAH + vehicle group (P ＜ 0.05).The Caspase-3 positive cell rate of in the hippocampus in SAH + methazolamide group was lower than in SAH + vehicle group (P ＜ 0.05).Conclusion Methazolamide can improve cognitive function of SAH mice possibly by inhibiting activation of Caspase-3,and the apoptosis of hippocampal neurons. Key words: Methazolamide;  Subarachnoid hemorrhage;  Cognitive function;  Apoptosis