Abstracts

Rationale: Lacosamide is an antiepileptic drug which enhances slow inactivation of sodium channels. The neuroprotective effect of lacosamide was investigated in a neonatal rat model of hypoxic-ischemic encephalopathy (HIE). Methods: HIE was induced in rats at day 7 of postnatal age by cauterization of the right common carotid artery, followed by 2 h 30 min of hypoxia using 8% oxygen. Immediately before and after the hypoxia-ischemia (pre-treatment group), and immediately after and 2 hours later (post-treatment group), the rats were fed with lacosamide (100 mg/kg/dose) through an orogastric tube. Controls received saline only. On postnatal day 12, brains were removed and gross morphological damage was evaluated. To quantify the severity of brain injury, bilateral cross-sectional areas of the anterior commissural and posterior hippocampal levels were analyzed using ImageJ software. Assessments of the open field activity levels at 2, 4, 6 and 8 weeks and, the Morris water maze test at 8weeks after hypoxia-ischemia were carried out according to standard methods to see the motor activity and cognitive function. Results: Lacosamide pre-treatment decreased the incidence of liquefactive cerebral infarction, at a dose of 100 mg/kg/dose (P<0.05). However, no benefit was observed in post-treatment group. In the Morris water maze test, the group pretreated with lacosamide at 100 mg/kg/dose showed shorter escape latencies than controls (P<0.05). Conclusions: Our results suggest that lacosamide pre-treatment is neuroprotective. Pre-treatment regimens could be clinically relevant in settings in which an increased risk of cerebral ischemia can be anticipated, such as in infants undergoing surgery to correct congenital heart disease.