Na+/Ca2+ exchanger in Na+ efflux-Ca2+ influx mode of operation exerts a neuroprotective role in cellular models of in vitro anoxia and in vivo cerebral ischemia.

The Na+/Ca2+ exchanger (NCX) plays a fundamental role in controlling intracellular levels of Na+ and Ca2+ in neuronal cells.1 Because under anoxic/ischemic conditions the intracellular homeostasis of these cations is altered, the role played by NCX in conditions of cellular anoxia or in vivo cerebral ischemia was evaluated. Primary culture of cortical neurons and C6 glioma cells, which can express the same Na+/Ca2+ exchanger isoform (NCX1) of astrocytes, were exposed to chemical hypoxia and intracerebroventricularly cannulated rats were exposed to permanent middle cerebral artery occlusion (pMCAO.). It was recently reported that sodium nitroprusside (SNP), a nitric oxide (NO)-generating compound, possesses the ability to activate the Na+/Ca2+ exchanger in cultured rat astrocytes.3 On the other hand, the SNP molecule contains iron besides the NO group. This metal ion, mediating the transfer of electrons between the cellular redox compounds and appropriate disulfide-thiol groups of the NCX molecule, can stimulate antiporter activity.4 Therefore, we investigated whether: (a) SNP could prevent chemical hypoxia-induced C6 glioma cell death, (b) this neuroprotective action was due to a stimulation of the Na+/Ca2+ exchanger activity, and (c) these effects were due to the NO donor property or the iron-releasing effect of SNP. To extrapolate these in vitro observations on the role played by the Na+/Ca2+ exchanger during anoxia to in vivo models of cerebral ischemia, pMCAO was performed in male rats.