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 necrotic and apoptotic components. Here we determined whether internucleosomal DNA fragmentation reflects the severity of SE-induced neuronal damage. We utilized both a systemic (kainic acid) and a focally-induced model of SE in 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 electrophoresis and quantified by liquid scintillation counting. The spatial and temporal characteristics of the SE-evoked DNA fragmentation indicated that this marker of apoptosis appears as early as 8 h after SE and reaches peak expression at 48 h. This method permitted us to quantitatively monitor the evolution 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 varied directly as a linear function of the duration of SE between 30 and 120 min suggesting that this marker should be highly responsive to neuroprotective intervention.
Kondratyev
A
A
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA. kondrata@medlib.georgetown.edu
Gale
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001923:Brain Chemistry; D004247:DNA / Q000235:genetics; D053938:DNA Fragmentation / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D007608:Kainic Acid; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
D018690:Excitatory Amino Acid Agonists; D004247:DNA; D007608:Kainic Acid