Neuroprotective activity of stiripentol with a possible involvement of voltage-dependent calcium and sodium channels
| Autor: | Marc, Verleye, Dorothée, Buttigieg, Rémy, Steinschneider |
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| Rok vydání: | 2015 |
| Předmět: |
Cerebral Cortex
Neurons Brain-Derived Neurotrophic Factor Sodium Glutamic Acid Dioxolanes Hirudins Embryo Mammalian Tritium Hippocampus Recombinant Proteins Rats Mice Inbred C57BL Glucose Neuroprotective Agents Fibrinolytic Agents Receptors Glutamate Neurofilament Proteins Animals Calcium Neuroglia alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Cells Cultured Protein Binding |
| Zdroj: | Journal of neuroscience research. 94(2) |
| ISSN: | 1097-4547 |
| Popis: | A growing body of data has shown that recurrent epileptic seizures may be caused by an excessive release of the excitatory neurotransmitter glutamate in the brain. Glutamatergic overstimulation results in massive neuronal influxes of calcium and sodium through N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainic acid glutamate subtype receptors and also through voltage-gated calcium and sodium channels. These persistent and abnormal sodium and calcium entry points have deleterious consequences (neurotoxicity) for neuronal function. The therapeutic value of an antiepileptic drug would include not only control of seizure activity but also protection of neuronal tissue. The present study examines the in vitro neuroprotective effects of stiripentol, an antiepileptic compound with γ-aminobutyric acidergic properties, on neuronal-astroglial cultures from rat cerebral cortex exposed to oxygen-glucose deprivation (OGD) or to glutamate (40 µM for 20 min), two in vitro models of brain injury. In addition, the affinity of stiripentol for the different glutamate receptor subtypes and the interaction with the cell influx of Na(+) and of Ca(2+) enhanced by veratridine and NMDA, respectively, are assessed. Stiripentol (10-100 µM) included in the culture medium during OGD or with glutamate significantly increased the number of surviving neurons relative to controls. Stiripentol displayed no binding affinity for different subtypes of glutamate receptors (IC50 100 µM) but significantly blocked the entry of Na(+) and Ca(2+) activated by veratridine and NMDA, respectively. These results suggest that Na(+) and Ca(2+) channels could contribute to the neuroprotective properties of sitiripentol. |
| Databáze: | OpenAIRE |
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