title: Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia.
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.
authors.affiliation: Department of Emergency Medicine, Gangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 07441, South Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Bich Na
authors.initials: BN
authors.lastname: Shin
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Tae-Kyeong
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea. mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Institute of Integrative Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, 225001, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Dongtan Sacred Heart Hospital, School of Medicine, Hallym University, Hwaseong, 18450, South Korea. pedkimsk@gmail.com.
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism*; D004195:Disease Models, Animal; D005849:Gerbillinae; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D000078334:Lacosamide; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: D000081:Acetamides; D000975:Antioxidants; D018696:Neuroprotective Agents; D000078334:Lacosamide; D002374:Catalase; D005979:Glutathione Peroxidase
keywords: Antiepileptic drug; Antioxidants; Lacosamide; Neuroprotection; Pyramidal neurons; Transient global cerebral ischemia