Neuroprotective activity of stiripentol with a possible involvement of voltage-dependent calcium and sodium channels
| Autor: | Dorothée Buttigieg, Marc Verleye, Rémy Steinschneider |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Kainic acid Chemistry Neurotoxicity Glutamate receptor Glutamic acid Pharmacology medicine.disease Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine nervous system medicine NMDA receptor Veratridine 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Research. 94:179-189 |
| ISSN: | 0360-4012 |
| DOI: | 10.1002/jnr.23688 |
| 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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