Valproate Suppresses Status Epilepticus Induced by 4-Aminopyridine in CA1 Hippocampus Region

Abstract

Purpose: We investigated the effects of valproate (VPA) on an in vivo model of status epilepticus (SE) induced by intrahippocampal application of 4-aminopyridine (4-AP). Methods: To induce continuous epileptiform activity without a clinical component, 4-AP (100 mM) was slowly injected in the hippocampus of adult rats. Extracellular field potential from the CA1 region of the rat hippocampus was recorded to assess abnormal epileptiform activity. Once the SE seizures were induced by 4-AP, the test drug was injected. In some experiments to test the ability of a drug to prevent the induction of SE, the drug was administered before 4-AP injection. Results: Intrahippocampal injection of 4-AP induced continuous epileptic activity without a clinical component that lasted >60 min. The intravenous injection of 400-600 mg/kg VPA rapidly (∼100 s) abolished the SE, and this effect persisted for ≥ 4 h in our experimental model. The intravenous injection of 100-300 mg/kg VPA did not abolish previously induced SE, but prevented the appearance of SE when applied before the induction of SE. The intravenous injection of 80 mg/kg phenytoin or carbamazepine did not abolish or prevent SE. Conclusions: We conclude that 4-AP-induced SE was suppressed by VPA at 400-600 mg/kg, whereas minor doses (100-300 mg/kg) only prevent the 4-AP-induced SE. Present results suggest the revisiting of VPA as a useful drug for the treatment of SE.