Abstracts

Prolonged seizures in adults can damage the hippocampus and cause epilepsy. However, the effects of prolonged seizures on the immature brain remain poorly understood. A small number of studies have suggested seizures in rats [lt]P14 cause damage, however the date at which vulnerability emerges is contraversial. If these seizures were able to cause hippocampal sclerosis, a characteristic of temporal lobe epilepsy (TLE), this could have significant implications for seizure treatment and approaches to anti-epileptogenesis., We have developed a novel animal model in P10 Sprague-Dawley rat pups that provides the unique ability to investigate the molecular pathogenesis of hippocampal sclerosis following seizures in the developing brain. The model features early-life prolonged seizures, induced by intraamygdalar injection of kainic acid (KA), that trigger acute neuronal death in the hippocampus, leading to hippocampal sclerosis at adulthood. EEG was recorded both acutely and over a period of weeks at adulthood to confirm the presence of seizures., Seizures were induced and hippocampal injury was then examined at various time points thereafter. Seizures induced largely unilateral hippocampal damage, affecting CA1 and CA3 regions. Western blot revealed that cell death was associated with activation of apoptotic pathways. By adulthood animals exhibited profound unilateral hippocampal sclerosis. Long-term EEG confirmed the presence of spontaneous seizures in these animals. Administration of a neuroprotectant FK506 during the initial seizures provided protection from hippocampal sclerosis at adulthood., We have successfully developed a novel model of unilateral hippocampal sclerosis and TLE in P10 rat pups. Using this model valuable insights may be gained into epileptogenesis in the developing brain and provide targets for anti-epileptogenic treatments., (Supported by Wellcome Trust and NIH.)