Abstracts

Early life status epilepticus is detrimental to the behavioral and cognitive development in childhood and increases the risk to develop epilepsy in later life. Recurrent seizures during the first two weeks of life in rats induce limited neuronal injury and synaptic reorganization of the mossy fiber pathway in the CA3 region of the hippocampus (Holmes et. al., 1999; Cilio et. al., 2003). These neurobiological alterations enhance the degree of neuronal injury and the duration of status epilepticus experienced after a second excitotoxic injury later in life (Koh et al., 1999; Schmid et al., 1999). The present study examines the frequency of late spontaneous seizures one year after early life kainic acid induced status epilepticus., Kainic acid was administered in age specific doses for the following experiments. On postnatal day (P) 15, kainic acid was administered to induce convulsive status epilepticus and control rats received equal volumes of saline. On P45, half of rats from each group received kainic acid induced status epilepticus. Status Epilepticus was monitored for 6 hours and behavioral seizures were scored using a previously described scale. These four groups were allowed to mature for 1 year and then underwent surgical implantation of bipolar hippocampal electrodes to monitor the occurrence of late onset spontaneous seizures. Rats were then monitored for 8 hours to determine the frequency of late onset spontaneous seizures. After rats were monitored they were perfused with sodium sulphide and paraformaldehyde / gluteraldehyde for histological examination with Timm[apos]s reagent and Cresyl Violet., After one year of maturation, rats that received kainic acid or saline on P15, did not demonstrate late onset spontaneous seizures over several 8 hour monitoring sessions, however mossy fiber sprouting was detected in the oriens of the CA3b region. Rats that receive saline on P15 and kainic acid on P45 developed late onset spontaneous seizures with an hourly seizure frequency of 0.22 [plusmn] 0.13 (mean [plusmn] SEM). This excitotoxic insult induced neuronal injury and synaptic reorganization of the mossy fiber pathway into the dentate gyrus and CA3b regions. Rats that received a [ldquo]double hit[rdquo] kainic acid on P15 and P45 developed severe late onset spontaneous seizures, with an hourly seizure frequency of 0.62 [plusmn] 0.31. These rats also developed widespread neuronal injury and synaptic reorganization of the mossy fiber pathway into the dentate gyrus and the CA3b regions., Early life status epilepticus induced by kainic acid induces limited neuronal injury and synaptic reorganization in the CA3b region, which is not sufficient to initiate the process of epileptogenesis. However, alterations after early life seizures shift the neurobiology in a pro-epileptic direction that enhances the susceptibility to seizures and accelerates epileptogenesis after subsequent insults during adulthood.,