Abstracts

Rationale: Neonatal or fetal asphyxia with resultant hypoxic-ischemic (HI) encephalopathy is an important cause of mortality and disability from cerebral palsy, seizures and mental retardation. We wondered if susceptibility to seizures in adults was related to effects of HI in the neonatal period. We used a standard rodent model of neonatal HI encephalopathy to evaluate seizure susceptibility and kindling in rats who matured following brain injury. Methods: Rat at PN 7 underwent common carotid artery ligation and exposure to hypoxia in an 8% oxygen environment for one hour. Controls were sham-operated animals. Once mature at 8 weeks, rats were assessed with response to pentylenetetrazol (PTZ) (50 mg/kg, i.p.) and to the ability to kindle rats with sequential injections of PTZ at 40 mg/kg per day by i.p. Redox function was evaluated using electron spin resonance. Results: Mature rats with an HI injury when neonates were susceptible to seizures induced by PTZ. However, these animals showed resistance to kindling when compared to controls (see Figure). Shift in redox was to oxidation in adult HI animals. Conclusions: In general, shifting redox toward oxidation enhances occurrence of seizures but associated suppression of Ca++ influx into neurons through NMDA receptor activation proves to be a rate-limiting factor in kindling development. We wonder if alterations in redox potential in vulnerable animals would have an effect on epileptogenesis. Funds; This study was partially supported by a Grant-in-Aid for Scientific Research (C)(2) (20591372 to Y.U.)