Age dependence of seizure-induced oxidative stress.
The mechanisms underlying the decreased vulnerability of the immature brain to seizure-induced neuronal death remain unknown. We asked whether oxidative stress plays a role in the resistance of immature animals to seizure-induced brain damage. Mitochondrial aconitase inactivation and 8-hydroxy-2-deoxyguanosine (8-OHdG) were used as indices of steady-state mitochondrial superoxide (O(2)(-)) production and oxidative DNA damage, respectively. Kainate-induced seizures resulted in increased mitochondrial aconitase inactivation and 8-OHdG formation in adult (postnatal day 30 or more), but not in immature rats (postnatal days 12 and 21). Kainate administration did not induce manganese superoxide dismutase (MnSOD) or CuZnSOD in immature or adult rats. This developmental increase in mitochondrial O(2)(-) production and oxidative DNA damage following kainate seizures suggests that mitochondrial oxidative stress may be a key factor that renders the developing brain resistant to seizure-induced brain damage.
Patel
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Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C238, Denver, CO 80262, USA. manisha.patel@uchsc.edu
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D000154:Aconitate Hydratase / Q000378:metabolism; D000375:Aging; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D005649:Fumarate Hydratase / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D015151:Immunoblotting; D007608:Kainic Acid / Q000009:adverse effects; D008928:Mitochondria / Q000201:enzymology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D013481:Superoxides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase; D003849:Deoxyguanosine; D007608:Kainic Acid