N w‐Propyl‐l‐arginine (L‐NPA) reduces status epilepticus and early epileptogenic events in a mouse model of epilepsy: behavioural, EEG and immunohistochemical analyses

摘要: We investigated the anticonvulsant and neurobiological effects of a highly selective neuronal nitric oxide synthase (nNOS) inhibitor, N w -propyl-l-arginine (L-NPA), on kainic acid (KA)-induced status epilepticus (SE) early epileptogenesis in C57BL ⁄6J mice. SE was induced with 20 mg ⁄kg KA (i.p.) seizures terminated after 2 h diazepam (10 ⁄kg, i.p). L-NPA (20 i.p.) or vehicle administered 30 min before KA. Behavioural seizure severity scored using modified Racine score electrographic recorded an implantable telemetry device. Neuronal activity, activity-dependent synaptogenesis reactive gliosis were quantified immunohistochemically, c-Fos, synaptophysin microglial astrocytic markers. treatment reduced duration convulsive motor seizures, power electroencephalogram gamma band, frequency epileptiform spikes during SE. It also c-Fos expression dentate granule cells at post-KA, overall rate spiking (by 2- to 2.5-fold) first 7 days administration. Furthermore, suppressed both hippocampal outer middle molecular layers gyrus phase (72 post-KA). These results suggest that nNOS facilitates generation may be important for changes associated development chronic epilepsy, especially stages epileptogenesis. As such, it might represent novel target disease modification epilepsy.