ANATOMICAL STUDIES OF DNA FRAGMENTATION IN RAT-BRAIN AFTER SYSTEMIC KAINATE ADMINISTRATION

Rats treated systemically with kainate develop stereotyped epileptic s eizures involving mainly limbic structures that may last for hours. Th is model of limbic status epilepticus has been widely studied using cl assical neuropathological techniques. We used in situ nick translation histochemistry to examine patterns of DNA fragmentation in this model . We found a stereotyped and reproducible pattern of neuronal populati ons that demonstrate evidence of DNA fragmentation from 24 h to one we ek after kainate treatment. Neither blockade of new protein synthesis nor blockade of the N-methyl-D-aspartate-type glutamate receptors sign ificantly altered this response. Moreover, we saw no evidence of the r egular internucleosomal cleavage of DNA that produces a characteristic laddered appearance of 180-200 bp DNA fragments after gel electrophor esis in samples obtained from microdissected affected regions. These s tudies suggest that DNA fragmentation after systemic kainate-induced s eizures is not the result of programmed cell death. This assay may be useful for quantitative testing of both neuroprotective agents and mec hanistic hypotheses. Copyright (C) 1996 IBRO. Published by Elsevier Sc ience Ltd.