title: Seizure-induced changes in energy metabolites and effects of N-tert-butyl-α-phenylnitrone (PNB) and vitamin E in rats.
abstract: Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of KA (15 mg/kg, sc) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h after the onset of SE using a head focused microwave technique and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex (23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced values returned to normal. Pretreatment of rats with an antioxidant (PBN, 200 mg/kg, ip, 30 min prior to KA; or vitamin E (Vit-E), 100 mg/kg, ip/day for 3 days), which did not prevent seizure activity, attenuated depletion of high-energy phosphates caused by KA. These findings suggest that the depletion of energy metabolites caused by KA-induced seizures may be linked to oxidative stress mediated toxicity.
authors.affiliation: Murray State University, Hopkinsville, KY 42241, USA, USA.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.affiliation: Departments of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Milatovic
authors.affiliation: University of Ljubljana, Medical School, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Zivin
authors.affiliation: Departments of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA, USA.
authors.forename: Wolf-D
authors.initials: WD
authors.lastname: Dettbarn
keywords: Key words seizures; high-energy phosphates; kainic acid (KA); oxidative stress