title: Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
authors.forename: Gun Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Byeon
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. bleun@korea.ac.kr.
authors.forename: Baik Lin
authors.initials: BL
authors.lastname: Eun
keywords: brain; hypoxia-ischemia; lacosamide; neuroprotection; newborn; rat