Modulation of no signaling pathways in an experimental model of epilepsy: Focus on ictal EEG

Abstract

One of the EEG hallmarks of homocysteine thiolactone (HcT)-induced epilepsy is spike-and-wave discharges (SWD). Nitric oxide (NO) is gasotransmitter produced by neuronal, endothelial and inducible NO synthesis (NOS). Contribution of NO-mediated signaling in epileptogenesis is unclear. The aim of our experiments were to compare the effects of non-selective (L-NAME) and selective (7-nitroindazole for neuronal and aminoguanidine for inducible) NOS inhibitors on ictal EEG phenomena in a model of HcT-induced epilepsy in rats. Male Wistar rats with implanted EEG-recording electrodes were intraperitoneally treated with HcT (subconvulsive dose of 5.5 mmol/kg) and EEG activity was recorded during next 90 min. L-NAME (700 mg/kg), 7-nitroindazole (75 mg/kg), aminoguanidine (100 mg/kg) or saline were injected 30 min prior to HcT administration. Visual inspection of digital EEG signals and analysis of number and duration of SWDs was performed offline. L-NAME significantly increased the number of SWDs per rat induced by HcT, but did not affect its duration. 7-nitroindazole increased duration, but not the number of SWDs in this model. Aminoguanidine increased both parameters significantly. These results indicated that modulation of NO-singaling pathways could affect EEG manifestations of HcT epilepsy showing contribution of this gasotransmitter in epileptogenesis and prominent effects of iNOS inhibition.