Neuroprotective effect of lacosamide on hypoxic-ischemic brain injury in neonatal rats

Gun Ha Kim, Jung Hye Byeon, Baik Lin Eun

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and Purpose Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of traumatic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. Methods We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia. Results The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/ dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats. Conclusions This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic conditions including heart surgery.

Original languageEnglish
Pages (from-to)138-143
Number of pages6
JournalJournal of Clinical Neurology (Korea)
Volume13
Issue number2
DOIs
Publication statusPublished - 2017 Apr

Keywords

  • Brain
  • Hypoxia-ischemia
  • Lacosamide
  • Neuroprotection
  • Newborn
  • Rat

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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