Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures.
We attempted to obtain evidence for the occurrence of oxidant injury following seizure activity by measuring hippocampal F2-isoprostanes (F2-IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F2-IsoPs esterified in hippocampal phospholipids was correlated with hippocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production in the kainate model. F2-IsoPs were measured in microdissected hippocampal CA1, CA3 and dentate gyrus (DG) regions at various times following kainate administration. Kainate produced a large increase in F2-IsoP levels in the highly vulnerable CA3 region 16 h post injection. The CA1 region showed small, but statistically insignificant increases in F2-IsoP levels. Interestingly, the DG, a region resistant to kainate-induced neuronal death also showed marked (2.5-5-fold) increases in F2-IsoP levels 8, 16, and 24 h post injection. The increases in F2-Isop levels in CA3 and DG were accompanied by inactivation of mitochondrial aconitase in these regions. This marked subregion-specific increase in F2-Isop following kainate administration suggests that oxidative lipid damage results from seizure activity and may play an important role in seizure-induced death of vulnerable neurons.
Patel
M
M
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. patelm@njc.org
Liang
L P
LP
Roberts
L J
LJ
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D028441:F2-Isoprostanes / Q000096:biosynthesis*; D005649:Fumarate Hydratase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D028441:F2-Isoprostanes; D013481:Superoxides; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase; D007608:Kainic Acid