Neuroprotective Effects Of Edaravone Combined With Nimodipine After Subarachnoid Hemorrhage In Rats

OBJECTIVE: To observe the neuroprotective effects and mechanisms of edaravone combined with nimodipine on hippocampal neurons in rats with subarachnoid hemorrhage. METHODS: 24 SD male rats(300-400g) were randomly divided into 4 groups, namely sham-operated group; subarachnoid hemorrhage (SAH) model group; nimodipine group; edaravone combined with nimodipine group there are 6 rats in every group; The latter two groups were received intraperitoneal with injection nimodipine 1mg/k only; intraperitoneal injection and edaravone 3mg/kg and nimodipine 1mg/kg respectively at the immediate moment of operation; the model group and sham-operated group were given the same dose of Sodium Chloride (6.5ml/kg) in the same way. Drugs were given again with the same dose and way after 24h. Immunohistochemical methods and western Blot were used to measure caspase-3 and Bcl-2 content in the hippocampus. RESULTS: The expression of caspase-3 of hippocampal neurons by immunohistochemical methods was significantly higher in model group than that in sham-operated group(P<0.01); but lower nimodipine group and combined drugs group (P<0.05, P<0.01); and the combined drugs group was lower than that in nimodipine drug group(P<0.05). The expression of bcl-2 of hippocampal neurons was significantly higher in model group than that in sham-operated group (P<0.01) but higher nimodipine groupand combined drugs group (P<0.05, P<0.01); and the combined drugs group were significantly higher than that in nimodipine drug group(P<0.01). The expression of caspase-3 in hippocampal neurons by Western Blot was significantly higher in model group than that in sham-operated group (P<0.01); but lower nimodipine group and combined drugs group (P<0.05, P<0.01); and the combined drugs group was significantly lower than that in nimodipine drug group(P<0.05). The expression of bcl-2 of hippocampal neurons were significantly higher in model group than that in sham-operated group (P<0.05) but higher nimodipine group and combined drugs group (P<0.05, P<0.01); and the combined drugs group were higher than that in nimodipine drug group(P<0.05) .The SOD content of hippocampal neurons were significantly lower in model group than those in sham-operated group (P<0.01) but higher nimodipine groupand combined drugs group (P<0.01, P<0.05); and the combined drugs group were higher than that in nimodipine drug group(P<0.05) The MDA content of hippocampal neurons were significantly higher in model groupthan those in sham-operated group (P<0.01) but lower nimodipine groupand combined drugs group (P<0.01, P<0.05); and the combined drugs group were higher than that in nimodipine drug group(P<0.05). CONCLUSION: Combined edaravone with nimodipine and single nimodipine use may increase the expression of bcl-2, SOD and reducing the expression of caspase-3, MDA on the injuried of hippocampal neurons after subarachnoid hemorrhage in rats. Edaravone combing nimodipine may has more neuroprotective effects.