Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus

The effects of kainic acid (KA)-induced limbic seizures have been investiga ted on cytochrome c oxidase (COx) activity, COx subunit IV mRNA abundance, ATP and phosphocreatine (PCr) levels in amygdala, hippocampus and frontal c ortex of rat brain. Rats were killed either 1 h, three days or seven days a fter the onset of status epilepticus (SE) by CO, and decapitation for the a ssay of COx activity and by head-focused microwave for the determination of ATP and PCr. Within I h COx activity and COx subunit IV mRNA increased in all brain areas tested between 120% and 130% of control activity, followed by a significant reduction from control, in amygdala and hippocampus on day three and seven, respectively. In amygdala, ATP and PCr levels were reduce d to 44% and 49% of control 1 h after seizures. No significant recovery was seen on day three or seven. Pretreatment of rats-with the spin trapping ag ent N-tert-butyl-alpha -phenylnitrone (PBN, 200 mg kg(-1), i.p.) 30 min bef ore KA administration had no effect on SE, but protected COx activity and a ttenuated changes in energy metabolites. Pretreatment for three days with t he endogenous antioxidant vitamin E (Vit-E, 100 mg/kg, i.p.) had an even gr eater protective effect than PBN. Both pretreatment regimens attenuated KA- induced neurodegenerative changes, as assessed by histology and prevention of the decrease of COx subunit IV mRNA and COx activity in hippocampus and amygdala, otherwise seen following KA-treatment alone. These findings sugge st a close relationship between SE-induced neuronal injury and deficits in energy metabolism due to mitochondrial dysfunction. (C) 2001 Elsevier Scien ce B.V. All rights reserved.