Abstracts

Lamotrigine (LTG) is a new antiepileptic drug indicated in all kinds of partial and generalised seizures, both in monotherapy and polytherapy. It is a presynaptic sodium channel blocker, thereby inhibits glutamate release. We tested whether it would protect against hypoxic-ischemic (HI) brain injury by LTG in postnatal day 7 Sprague-Dawley rats. Right common carotid artery of the rat was coagulated and then the rat was exposed to 8% oxygen for 2 hrs. LTG (20, 50, 100, 200 mg/kg, every 12 hrs for 5 days) administered by nasogastric tube in pre- (n=35) and post-treatment (n=35) regimens, and controls (n=60) received normal saline. Severity of injury was assessed 5 days later by visual evaluation of ipsilateral hemispheric infarction, and by measurement of bilateral hemispheric cross sectional areas. LTG pretreatment resulted in a decreased incidence of liquefactive cerebral infarction (P[lt]0.05). Quantitation of hemispheric areas in rats receiving TPM and control littermates confirmed the results of initial inspection (P[lt]0.01). Pretreatment with LTG decreases the incidence and severity of ischemic brain damage in this animal model of perinatal cerebral hypoxia-ischemia. These data indicate that LTG plays a role in the evolution of HI injury to the developing brain, and that LTG pretreatment may offer an effective means to decrease the incidence and severity of perinatal HI brain injury. (Supported by Health Technology Planning and Evaluation Board Project-Grant 02-PJ1-PG1-CH06-0001)