Sunday July 2, 2006 7:30-9:00 Hall 5C Teaching Session Nonconvulsive status epilepticus - clinical definitions and biological framework

Abstract

Abstract 1 J. Epsztein ( 1 INMED-INSERM U29, France ) Ongoing epileptiform activity without seizures in the postischemic hippocampus: a permanent shift of the excitatory-inhibitory synaptic balance in resistant pyramidal neurons Ischemic stroke are often associated to late-onset epilepsy but the underlying mechanisms are poorly understood. In the hippocampus, that is one of the regions most sensitive to ischemic challenge, global ischemia induces a specific neuronal loss of CA1 pyramidal neurons while the resistant CA3 pyramidal neurons display a long-term hyperexcitability several months after the insult. The mechanisms of this long-term hyperexcitability remain unknown despite their clinical implications. The aim of the present report was to analyze the long-term morpho-functional consequences of global ischemia on glutamatergic and GABAergic systems in the CA3 area of the hippocampus that could account for the hyperexcitability of resistant CA3 pyramidal cells. Using chronic in vivo EEG recordings and in vitro field recordings in slices, we report spontaneous interictal epileptiform discharges (IEDs) in the CA3 area of the hippocampus from post ischemic rats several months after the insult. However, none of the recorded postischemic rats showed behavioral or electrographic seizures in the hippocampus during the recording period. Whole cell recordings from CA3 pyramidal neurons revealed a permanent reduction in the frequency of spontaneous and miniature GABAergic inhibitory postsynaptic currents (IPSCs) and a parallel increase in the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (EPSCs). Global ischemia also induced a dramatic loss of GABAergic interneurons and terminals together with an increase in glutamatergic terminals in the CA3 area of the hippocampus. Altogether our results show a morpho-functional reorganization in the CA3 network several months after global ischemia resulting in a net shift in the excitatory-inhibitory balance towards excitation that may constitute a substrate for the generation of epileptiform discharges in the post-ischemic hippocampus.