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

Neurochem Res. 2016 Sep;41(9):2380-90. doi: 10.1007/s11064-016-1951-8. Epub 2016 May 21.

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.

Keywords: Antiepileptic drug; Antioxidants; Lacosamide; Neuroprotection; Pyramidal neurons; Transient global cerebral ischemia.

MeSH terms

  • Acetamides / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Catalase / metabolism*
  • Disease Models, Animal
  • Gerbillinae
  • Glutathione Peroxidase / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Ischemic Attack, Transient / metabolism*
  • Lacosamide
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Reperfusion Injury / metabolism

Substances

  • Acetamides
  • Antioxidants
  • Neuroprotective Agents
  • Lacosamide
  • Catalase
  • Glutathione Peroxidase