Temporal and spatial patterns of DNA fragmentation following focally or systemically-evoked status epilepticus in rats

Status epilepticus (SE) triggers neuronal degeneration comprised of both ne crotic and apoptotic components. Here we determined whether internucleosoma l DNA fragmentation reflects the severity of SE-induced neuronal damage. We utilized both a systemic (kainic acid) and a focally-induced model of SE i n rats. DNA fragmentation was analyzed in rhinal cortex and hippocampus at various time points following SE episodes of varying durations (30-120 min) . Radioactively labeled DNA fragments were analyzed by agarose gel electrop horesis and quantified by liquid scintillation counting. The spatial and te mporal characteristics of the SE-evoked DNA fragmentation indicated that th is marker of apoptosis appears as early as 8 h after SE and reaches peak ex pression at 48 h. This method permitted us to quantitatively monitor the ev olution of the apoptotic component of cell death over the acute post-injury period (8-72 h). Moreover, in both models of SE, the DNA fragmentation var ied directly as a linear function of the duration of SE between 30 and 120 min suggesting that this marker should be highly responsive to neuroprotect ive intervention. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve d.