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Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia
Authors:Hyun Young Choi  Joon Ha Park  Bai Hui Chen  Bich Na Shin  Yun Lyul Lee  In Hye Kim  Jeong-Hwi Cho  Tae-Kyeong Lee  Jae-Chul Lee  Moo-Ho Won  Ji Hyeon Ahn  Hyun-Jin Tae  Bing Chun Yan  In Koo Hwang  Jun Hwi Cho  Young-Myeong Kim  Sung Koo Kim
Affiliation:1.Department of Emergency Medicine, Gangnam Sacred Heart Hospital, College of Medicine,Hallym University,Seoul,South Korea;2.Department of Neurobiology, School of Medicine,Kangwon National University,Chuncheon,South Korea;3.Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine,Hallym University,Chuncheon,South Korea;4.Department of Biomedical Science, Research Institute of Bioscience and Biotechnology,Hallym University,Chuncheon,South Korea;5.Institute of Integrative Traditional and Western Medicine, Medical College,Yangzhou University,Yangzhou,China;6.Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine,Seoul National University,Seoul,South Korea;7.Department of Emergency Medicine, School of Medicine,Kangwon National University,Chuncheon,South Korea;8.Department of Molecular and Cellular Biochemistry, School of Medicine,Kangwon National University,Chuncheon,South Korea;9.Department of Pediatrics, Dongtan Sacred Heart Hospital, School of Medicine,Hallym University,Hwaseong,South Korea
Abstract:Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin–eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment.
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