Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha-phenylnitrone (PNB) and vitamin E in rats

Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an ac ute dose of KA (15 mg/kg, sc) rats developed SE within 1 h. Rats were sacri ficed 1 or 72 h after the onset of SE using a head focused microwave techni que and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and c reatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were signi ficantly 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 nu cleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced va lues 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 h igh-energy phosphates caused by KA. These findings suggest that the depleti on of energy metabolites caused by KA-induced seizures may be linked to oxi dative stress mediated toxicity.