Recurrent Bicuculline-Induced Seizures in Rat Pups Cause Long-Term Motor Deficits and Increase Vulnerability to a Subsequent Insult

Recurrent neonatal seizures are associated with a high risk of neurological sequelae. The major concern is whether recurrent neonatal seizures induce adverse effects on long-term cognition and/or motor performance. Rats were treated with intraperitoneal (ip) bicuculline for 3 consecutive days, starting from Postnatal Day 5 (P5). Kainic acid (KA, 4 mg/kg ip) was injected at P53 to investigate the susceptibility to a second insult, and then cognitive function was tested using the Morris water maze, and motor performance using the Rotarod test, in adulthood (P60). Finally, histological assessments of brains were performed. The rats treated with bicuculline had no deficits in cognition function and pathology findings, but had worse motor performance and increased susceptibility to later KA challenge. Our findings indicate that recurrent bicuculline-induced seizures in the developing brain result in long-term motor deficits and increase the risk of subsequent cognitive damage in response to a second insult.