Cerebroprotective properties of lamotrigine in the developing brain after perinatal asphyxia: experimental study in rats

Introduction: Perinatal asphyxia leads to neuronal injury in several vulnerable regions of the brain, especially in the hippocampus. The injury is related to the toxic action of glutamate. Lamotrigine (Lam) is an antiepileptic drug that inhibits the release of glutamate. The purpose of our study was to evaluate the cerebroprotective properties of Lam in the hippocampus of the immature rat after perinatal asphyxia. MATERIALS AND Methods: In 7-day old rats a hypoxic-ischemic injury to the left cerebral hemisphere by left common carotid artery ligation was induced, followed by a one-hour exposure to hypoxia. Animals (n=30) were classified into three treatment groups and immediately after hypoxia were given intraperitoneally: (1)saline,(2) Lam at 10mg/kg,(3) Lam at 20mg/kg. Histological analysis was conducted 7 days after asphyxia. The severity of damage was assessed in CA1, CA3, CA4 regions of the hippocampus and the dentate gyrus(d.g.) by using light and electron microscopy. Results: In the control group, the most significant injury was indentified in CA1 region and to a lesser extend in d.g., CA3 and CA4. Lam at 10mg/kg reduced statistically significant the damaged neurons of the CA1 region. No effect was found in the other regions. Lam at 20mg/kg caused a significant decrease in the damaged neurons of the CA1 and CA3 regions as well as in the d.g. Discussion: Lam exerted a significant cerebroprotective effect on the CA1 and CA3 regions and the d.g. which was dosedependet.