Prevention Of Hippocampal Neuronal Damage And Cognitive Function Deficits In Vascular Dementia By Dextromethorphan

BACKGROUND Dextromethorphan(DM)is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine.Recently,its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease(PD)and multiple sclerosis(MS).OBJECTIVESIn this study,we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries(two-vessel occlusion [2VO]),an animal model of Vascular Dementia(VaD).METHODS Sprague-Dawley(SD)(10 weeks of age)rats were subjected to the 2VO,and DM was injected intraperitoneally once per day for 37 days.Neuron death,glial activation and cognitive function were assessed at 37 days after 2VO(0.2 mg/kg DM,i.p.,“DM-0.2” and 2 mg/kg DM,i.p.,“DM-2”).Furthermore,the mechnism of DM protection was investigated in the study.RESULTS The results showed that DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats assessed by the Water maze.The level of oxidase stress was assessed in the hippocampus,the results showed that the level of 4-HNE was decreased after the treatment of 0.2DM,.The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase play important roles in these effects.CONCLUSION These results suggest that DM is effective in treating VaD and protecting against oxidative stress,which is strongly implicated in the pathogenesis of VaD.Therefore,the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.