Kainate-induced seizures, oxidative stress and neuronal loss in aging rats.
Aging is a significant risk factor for developing epilepsy. The mechanisms underlying age-related increase in seizure susceptibility and resultant injury remain unknown. Oxidative stress is an important mechanism that contributes to diverse age-related disorders. Whether age-related increased seizure susceptibility is accompanied by increased oxidative stress remains unknown. The goal of this study was to determine if aging per se increases the susceptibility of rats to kainate-induced behavioral seizures and oxidative stress. Adult (3-4 month-old) and aging (18-19 month-old) Sprague-Dawley rats were administered a single low dose of kainate (5 mg/kg, s.c.) or saline. Behavioral seizures were monitored in all four groups for a period for a period of approximately 6 h. Oxidative stress (8-hydroxy-2'deoxyguanosine/2-deoxyguanosine; 8OHdG/2dG) was assessed 24 h following kainate injection. Stereological assessment of cell counts was performed in hippocampal tissue 7 days following kainate injection. In adult rats, administration of the low dose of kainate did not produce significant behavioral seizures, oxidative stress or cell loss. However, aging rats exhibited intense behavioral seizures consistent with status epilepticus following the low dose of kainate. In aging rats, kainate produced a significant increase in oxidative DNA damage (8OHdG/2dG) and neuronal loss in cornu ammonis regions 3 and 1 (CA3 and CA1), but not dentate gyrus compared with both age-matched controls and adult kainate-treated rats. These data suggest that the process of aging per se increases kainate-induced seizure susceptibility, oxidative stress and hippocampal pyramidal cell loss.
Liang
L P
LP
Department of Pharmaceutical Sciences, 4200 East Ninth Avenue, Box C238, Denver, CO 80262, USA.
Beaudoin
M E
ME
Fritz
M J
MJ
Fulton
R
R
Patel
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D013997:Time Factors
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D007608:Kainic Acid