Neurotoxicity of chronic aluminum overload and protective effects of nimodipine in rats / 第三军医大学学报

ABSTRACT

Objective To study the neurotoxicity of chronic aluminum overload and the protective effects of nimodipine in rats.Methods The brain damage models of rats were established via intragastric administration of aluminum gluconate(element aluminum 400 mg/kg)once a day,5 d/week for 12 weeks.The step-down test and programmed Morris water maze test were used to evaluate the changes of learning and memory functions of rats.Pathomorphological changes of hippocampi of rats were observed.The activities of SOD,ChAT,AchE,MAO-B and the contents of MDA of brain tissue in rats were also measured.Nimodipine(80 mg/kg)were intragastrically administered 4 h after aluminum administration every time for 12 weeks.Results Chronic aluminum administration induced the impairment of avoidance learning and memory ability and spatial oriental ability.Consistent with the behavioral changes,neuronal death in the hippocampi,decreased activities of SOD and ChAT,increased content of MDA,and increased activity of MAO-B and AchE were detected in the aluminum-overload mice.The administration of nimodipine could significantly protect rats from the brain damage,and behavioral and biochemical changes above caused by aluminum overload were in a dose-dependent manner.Conclusion These results suggest that changes of cellular calcium overload and oxide stress and MAO-B activities are involved in pathophysiological mechanisms of brain injury induced by chronic aluminum overload.Nimodipine has a protective effect on neurotoxicity of chronic aluminum overload.