S-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model.

Aims: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, downstream of the epidermal growth factor receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO.

Nitric oxide stimulates the proliferation of neural stem cells bypassing the epidermal growth factor receptor.

Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone.

Neurotoxicity induced by antiepileptic drugs in cultured hippocampal neurons: a comparative study between carbamazepine, oxcarbazepine, and two new putative antiepileptic drugs, BIA 2-024 and BIA 2-093.

Purpose: Newly designed antiepileptic drugs (AEDs) are being evaluated for their efficacy in preventing seizures and for their toxic profiles. We investigated and compared the toxic effects of two dibenz[b,f]azepine derivatives with anticonvulsant activity, 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5-carboxamide (BIA2-024) and (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f] azepine-5-carboxamide (BIA2-093), with the structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), both in current use for the treatment of epilepsy.

Methods: Primary rat hippocampal neurons were used to evaluate neuronal morphology and biochemical changes induced by the AEDs used in this study.