Abstracts

The acute brain insult, such as status epilepticus is followed by a latent period characterized by the functional or morphological changes of the hippocampus over several days to weeks, before the onset of spontaneous recurrent seizures. Although the significance of abnormal plasticity, such as cell genesis has been described in the hippocampus after seizures, little data so far ascertained the preventive strategies in epilepsy. We have tried to discover desirable drugs to rectify the abnormal plasticity for clinical use. Erythropoietin (EPO), recently known as cytoprotective and anti-inflammatory agent, and neurogenic modulator, may constitute an effective therapeutic modality in cases of epileptic insult. However, there is no study for the effects of exogenous EPO on the epileptogenic process., In this study, we examined the effects of EPO in the epileptic rats with lithium/pilocarpine-induced status epilepticus (SE), in terms of neuronal loss, inflammation, and cell proliferation ., The neuronal death, inflammation, and cell genesis was substantially linked together in more extensive areas, notably in entorhinal, perirhinal, piriform cortex, amygdala and parts of the thalamus as well as the hippocampus. The EPO receptor (EPOR) mRNA level was increased in the first week after SE, and decreased thereafter. EPOR was increased in the damaged areas such as hilus and CA1 subfield. During the latent period after pilocarpine-induced status epilepticus, EPO prevented neuronal death and microglia activation in these areas, and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1., These findings suggest a potential therapeutic role for EPO in chronic epilepsy. Currently, we are trying to disclose the agents potentially conferring anti-epileptogenesis in a variety of epilepsy models, including febrile convulsion and neocortical epilepsy., (Supported by the Ministry of Health and Welfare (A060452), Republic of Korea.: 1. Jung KH, Chu K, Kim M, Jeong SW, Song YM, Lee ST, Kim JY, Lee SK, Roh JK. Continuous cytosine-b-D-arabinofuranoside infusion reduces ectopic granule cells in adult rat hippocampus with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Eur J Neurosci. 2004;19:3219-3226. 2. Jung KH, Chu K, Lee ST, Kim J, Sinn DI, Kim JM, Park DK, Lee JJ, Kim SU, Kim M, Lee SK, Roh JK. Cyclooxygenase-2 inhibitor, Celecoxib Inhibits the Altered Hippocampal Neurogenesis with Attenuation of Spontaneous Recurrent Seizures Following Pilocarpine-Induced Status Epilepticus. Neurobiol Dis. 2006 (In press).)