Increased susceptibility to pentetrazol-induced seizures in developing rats after cortical photothrombotic ischemic stroke at P7

Abstract

Perinatal stroke is a common cerebrovascular disorder affecting 1 in every 4000 births; typically associated with epilepsy. We sought to determine seizure susceptibility to pentylentetrazol (PTZ)-induced seizures in developing rats with a history of photothrombotic lesion of sensorimotor cortex induced at postnatal day 7. Lesioned animals were tested at P12 or P25 and compared with sham-operated controls. Three models of epileptic seizures were elicited by PTZ: episodes of spike-and-wave rhythm, minimal clonic seizures and generalized tonic-clonic seizures. PTZ (60 and 100 mg/kg) was administered subcutaneously to assess seizure occurrence, latency and severity. In addition, episodes of rhythmic EEG activity were analyzed at P25 following successive interperitoneal 20 and 40 mg/kg PTZ administration. There was only one significant change in convulsive seizures--decreased latency of generalized seizures in lesioned 12-day-old animals. EEG study demonstrated marked difference between lesioned and control rats. Lesioned rats had longer latencies and longer durations of the first rhythmic episode (following 20 mg/kg PTZ) as compared to controls. After 40 mg/kg of PTZ, 7 in 8 leisioned and 1 in 8 control rats exhibited clonic seizures. Cortical ischemic lesion during early development affected differently the susceptibility of rat's brain to three types of PTZ-induced seizures 5 and 18 days post photothrombotic insults.