Abstracts

Hippocampal sclerosis is the commonest lesion identified in temporal lobe epilepsy and has been proposed as both cause and effect of seizures. Additionally, an emerging concept in epilepsy research is that the propagation of paroxysmal activity is necessary and sufficient to transform a na[iuml]ve structure into one that is capable of generating spontaneous (epileptic) seizures. This transformation underlies the formation of an epileptogenic focus that can entrain the generation of seizures in interconnected structures. However, whether seizure-injury occurs within such communicating fibre tracts is largely unknown but recent reports document the presence of lesions within white matter tracts in epilepsy patients. According, we evaluated white matter tract injury within the [italic]corpus callosum[/italic] in a novel seizure model in mice., Adult male C57Bl/6 mice underwent focally-evoked seizures induced by intraamygdala kainic acid microinjection with continuous electroencephalography. Seizures were terminated by intravenous lorazepam 40 (n=10) or 50 minutes (n=7) following kainate/vehicle (n=3) injection and brains obtained 24 hours later. Coronal sections were processed for detection of DNA fragmentation using the TUNEL technique. To identify the cell populations of the corpus callosum, the slides were labelled for oligodendrocytes with antibodies against 2,3-cyclic-nucleotide 3- phosphodiesterase (CNP) or myelin basic protein (MBP) and for astrocytes with anti-glial fibrillary acidic protein (GFAP)., Seizures in mice terminated after 40 min resulted predominantly in unilateral TUNEL staining within ipsilateral CA3 and CA1. In contrast, when seizure activity was extended to 50 min contralateral CA1 and CA3 hippocampal damage was more frequently observed. Examination of the ipsilateral and contralateral [italic]corpus callosum[/italic] revealed the presence of cell death. Our data also revealed significant correlations between numbers of degenerating cells in contralateral (r=0.460, p[lt]0.05) [italic]corpus callosum[/italic] and the severity of neuronal cell death in CA3 hippocampus ipsilateral. Seizures induced oligodendrocyte death in the corpus callosum as revealed by the immunofluorescence colocalization of TUNEL/MBP or CNP. In contrast, the presence of a gliogenesis is shown around the corpus callosum., The present data establish that prolonged focal limbic seizures in mice induce damage to non-neuronal elements within the corpus callosum and show the degree of this injury is a function of hippocampal damage. Our data indicate seizures injure white matter tracts and offer a potential mechanism for seizure generation and spread to contralateral and extrahippocampal structures., (Supported by Marie Curie Grant.)