title: Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.
abstract: 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). In 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). 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, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). 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. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. 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.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
authors.forename: Jiangshan
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, China.
authors.forename: Bing-Qiao
authors.initials: BQ
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China. zhaoyuwu2005@126.com.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D015140:Dementia, Vascular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D003915:Dextromethorphan / Q000494:pharmacology / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D065866:Optic Tract / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D066127:White Matter / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D003915:Dextromethorphan; D051547:Heme Oxygenase-1
keywords: Dextromethorphan; Microglial activation; Oxidative stress; Vascular dementia