Different effects between 7-nitroindazole and l-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits

Abstract

We examined the effects of 7-nitroindazole (7-NI) and N-ω-nitro- l-arginine methyl ester ( l-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), l-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO 2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or l-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by l-NAME. l-NAME pre-treatment caused a significant decrease in HbO 2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and l-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, l-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and l-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.