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Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia

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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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Acknowledgments

The authors would like to thank Mr. Seung Uk Lee for his technical help in this study. This work was supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (NRF-2015M3A9B6066835), by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (NRF-2014R1A2A2A01005307), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A1A2057092).

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    Authors and Affiliations

    1. Department of Emergency Medicine, Gangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 07441, South Korea

      Hyun Young Choi

    2. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea

      Joon Ha Park, In Hye Kim, Jeong-Hwi Cho, Tae-Kyeong Lee, Jae-Chul Lee & Moo-Ho Won

    3. Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea

      Bai Hui Chen, Bich Na Shin & Yun Lyul Lee

    4. Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea

      Ji Hyeon Ahn & Hyun-Jin Tae

    5. Institute of Integrative Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, 225001, China

      Bing Chun Yan

    6. Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

      In Koo Hwang

    7. Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea

      Jun Hwi Cho

    8. Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea

      Young-Myeong Kim

    9. Department of Pediatrics, Dongtan Sacred Heart Hospital, School of Medicine, Hallym University, Hwaseong, 18450, South Korea

      Sung Koo Kim

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    1. Hyun Young Choi
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    Correspondence to Moo-Ho Won or Sung Koo Kim.

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    The authors have no financial conflict of interest. The procedures for animal handling and care adhered to guidelines that are in compliance with the current international laws and policies (Guide for the Care and Use of Laboratory Animals, The National Academies Press, 8th Ed., 2011), and experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Kangwon National University. All of the experiments were conducted to minimize the number of animals used and the suffering caused by the procedures used in this study.

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    Hyun Young Choi and Joon Ha Park have contributed equally to this article.

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    Choi, H.Y., Park, J.H., Chen, B.H. et al. Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia. Neurochem Res 41, 2380–2390 (2016). https://doi.org/10.1007/s11064-016-1951-8

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