CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy

被引:111
作者
Gluck, MR
Jayatilleke, E
Shaw, S
Rowan, AJ
Haroutunian, V
机构
[1] Vet Adm Med Ctr, Dept Neurol, Bronx, NY 10468 USA
[2] Vet Adm Med Ctr, Dept Med, Bronx, NY 10468 USA
[3] Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA
关键词
kainic acid; oxidative stress; epilepsy; animal model; hippocampus; cortex;
D O I
10.1016/S0920-1211(99)00111-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The role of oxidative stress in seizure-induced brain injury was investigated in a kainic acid model of experimental epilepsy. Kainic acid (12.5 mg/kg) or saline was injected intraperitoneally into 12-week-old male Fischer 344 rats and sacrificed by decapitation at 4 and 24 h after injection. Markers of oxidative stress including protein carbonyls, thiobarbituric acid reactive material (TBARs), glutathione (GSH) and glutathione disulfide (GSSG) were measured in hippocampus, cortex, cerebellum and basal ganglia. Four hours after treatment, protein carbonyls were elevated by 103, 55, 52 and 32% in cortex, hippocampus, basal ganglia and cerebellum, respectively. TBARs were increased by 30-45% in all areas. After 24 h, elevated protein and lipid oxidative markers persisted in the hippocampus and cerebellum; by contrast, in the cortex, TBARs almost normalized to control values and protein carbonyls trended downward by one-half compared with measurements at 4 h, although this reduction relative to the 4 h timepoint did not reach statistical significance. In the basal ganglia, protein carbonyls approached control values at 24 h. GSSG levels were only increased statistically in the cortex after 4 h. GSH levels in all the regions were unchanged after treatment with kainic acid. However, in cortex, GSH levels correlated negatively with increases in protein and lipid oxidation (r = - 0.69, P < 0.002). In contrast, significant correlations between GSH, protein carbonyls and TBARs measured in the hippocampus or cerebellum were not observed. Our data suggests that kainic acid induced similar oxidative stress in all of the brain regions that were examined, and that GSH plays a major antioxidant role in the cerebral cortex but not the hippocampus. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:63 / 71
页数:9
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