Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats.
10.3988/jcn.2017.13.2.138
- Author:
Gun Ha KIM
1
;
Jung Hye BYEON
;
Baik Lin EUN
Author Information
1. Department of Pediatrics, Korea University College of Medicine, Seoul, Korea. bleun@korea.ac.kr
- Publication Type:Original Article
- Keywords:
brain;
hypoxia-ischemia;
lacosamide;
neuroprotection;
newborn;
rat
- MeSH:
Animals;
Brain Injuries*;
Brain*;
Carotid Arteries;
Cerebral Infarction;
Hippocampus;
Humans;
Incidence;
Infant, Newborn;
Memory;
Methods;
Mortality;
Neuroprotection;
Neuroprotective Agents*;
Oxygen;
Rats*;
Semaphorin-3A;
Sodium Channels;
Spatial Learning;
Status Epilepticus;
Thoracic Surgery;
Water
- From:Journal of Clinical Neurology
2017;13(2):138-143
- CountryRepublic of Korea
- Language:English
-
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.
