title: Edaravone injection reverses learning and memory deficits in a rat model of vascular dementia.
abstract: Edaravone is a novel free radical scavenger that exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Recently, it was reported that edaravone could alleviate the pathology and cognitive deficits of Alzheimer's disease patients. However, its relevance to vascular dementia (VaD) is not clear. In this study, we partially occluded the bilateral carotid arteries of rats surgically to induce chronic cerebral hypoperfusion (CCH), a well-known rat model of VaD. Water maze and step-down inhibitory test were used to evaluate the memory deficit. The activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH), the content of malondialdehyde (MDA) and total reactive oxygen species were measured to evaluate the oxidative stress level. Western blot analysis was used to evaluate the synaptic protein expression. It was found that treatment with edaravone for a 5-week period was able to reverse both spatial and fear-memory deficits in rats with CCH. Edaravone significantly reduced the level of oxidative stress in the brains of rats with CCH by increasing SOD activity and decreasing the content of MDA, LDH, and total reactive oxygen species. Furthermore, edaravone treatment also restored the levels of multiple synaptic proteins in the hippocampi of rats with CCH. Our data provide direct evidence supporting the neuroprotective effects of edaravone in VaD. We propose that the alleviation of oxidative stress and restoration of synaptic proteins play important roles in neuroprotection.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou 450008, China lixu06@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou 450008, China.
authors.forename: Qingkai
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Medical Development, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou 450008, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou 450008, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D000077553:Edaravone; D005239:Fear; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D000077553:Edaravone; D000983:Antipyrine
keywords: edaravone; memory; oxidative stress; vascular dementia