Role of neurosteroids in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked neuronal injury and behavioral deficits in mice

摘要

To investigate the role of neurosteroids in ischemic postconditioning-induced attenuation of cerebral ischemiaevoked neuronal injury and behavioral deficits in mice. Mice were randomly divided into four groups. Mice were subjected to 13min global cerebral ischemia followed by three episodes of 10s of ischemia and reperfusion for 24h. Metyrapone (100mg/kg), an inhibitor of 11β-hydroxylase, was administered 30 min prior to global cerebral ischemia and ischemic postconditioning. Finasteride (50mg/kg), an inhibitor of 5α-reductase, was administered 30 min prior to Metyrapone 100mg/kg and 1h before induction to global cerebral ischemia and ischemic postconditioning. The mice were exposed to elevated plus maze test for assessing transfer latency time to evaluate the short term memory. The rota rod, inclined beam walking test were used to evaluate motor coordination. Ischemic postconditioning significantly attenuated the ischemia-reperfusion-induced increase in cerebral infarct size measured by volume and weight method. Administration of metyrapone (100 mg/kg; i.p.), an inhibitor of 11β- hydroxylase, 30min before the induction of cerebral ischemia and ischemic postconditioning, significantly attenuated ischemia-reperfusion-induced increase in cerebral infarct size. It may be concluded that neurosteroids may be involved in neuroprotective mechanism of ischemic postconditioning as neurosteroids may be responsible for decrease in infarct size, improvement in motor performance and short term memory.