Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats
- Authors
- Kim, Gun-Ha; Byeon, Jung Hye; Eun, Baik-Lin
- Issue Date
- 4월-2017
- Publisher
- KOREAN NEUROLOGICAL ASSOC
- Keywords
- brain; hypoxia-ischemia; lacosamide; neuroprotection; newborn; rat
- Citation
- JOURNAL OF CLINICAL NEUROLOGY, v.13, no.2, pp.138 - 143
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- JOURNAL OF CLINICAL NEUROLOGY
- Volume
- 13
- Number
- 2
- Start Page
- 138
- End Page
- 143
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/83961
- DOI
- 10.3988/jcn.2017.13.2.138
- ISSN
- 1738-6586
- 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.
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