Author/Editor     Milatovič, Dejan; Živin, Marko; Gupta, Ramesh C; Dettbarn, Wolf D
Title     Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus
Type     članek
Source     Brain Res
Vol. and No.     Letnik 912, št. 1
Publication year     2001
Volume     str. 67-78
Language     eng
Abstract     The effects of kainic acid (KA)-induced limbic seizures have been investigated on cytochrome c oxidase (COx) activity, COx subunit IV mRNA abundance, ATP and phosphocreatine (PCr) levels in amygdala, hippocampus and frontal cortex of rat brain. Rats were killed either 1 h, three days or seven days after the onset of status epilepticus (SE) by CO(2) and decapitation for the assay of COx activity and by head-focused microwave for the determination of ATP and PCr. Within 1 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 reduced 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 agent N-tert-butyl-alpha-phenylnitrone (PBN, 200 mg kg(-1), i.p.) 30 min before KA administration had no effect on SE, but protected COx activity and attenuated changes in energy metabolites. Pretreatment for three days with the endogenous antioxidant vitamin E (Vit-E, 100 mg/kg, i.p.) had an even greater 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 suggest a close relationship between SE-induced neuronal injury and deficits in energy metabolism due to mitochondrial dysfunction.
Descriptors     STATUS EPILEPTICUS
KAINIC ACID
CYTOCHROME-C OXIDASE
RNA, MESSENGER
ADENOSINE TRIPHOSPHATE
RATS, SPRAGUE-DAWLEY
HISTOCYTOCHEMISTRY
PHOSPHOCREATINE
AMYGDALOID BODY
HIPPOCAMPUS
CEREBRAL CORTEX
VITAMIN E