PT - JOURNAL ARTICLE AU - Pasquale Molinaro AU - Ornella Cuomo AU - Giuseppe Pignataro AU - Francesca Boscia AU - Rossana Sirabella AU - Anna Pannaccione AU - Agnese Secondo AU - Antonella Scorziello AU - Annagrazia Adornetto AU - Rosaria Gala AU - Davide Viggiano AU - Sophie Sokolow AU - Andre Herchuelz AU - Stèphane Schurmans AU - Gianfranco Di Renzo AU - Lucio Annunziato TI - Targeted Disruption of Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger 3 (NCX3) Gene Leads to a Worsening of Ischemic Brain Damage AID - 10.1523/JNEUROSCI.4671-07.2008 DP - 2008 Jan 30 TA - The Journal of Neuroscience PG - 1179--1184 VI - 28 IP - 5 4099 - http://www.jneurosci.org/content/28/5/1179.short 4100 - http://www.jneurosci.org/content/28/5/1179.full SO - J. Neurosci.2008 Jan 30; 28 AB - Na+/Ca2+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly, whereas the function of NCX3 under physiological conditions has been determined, its role under anoxia is still unknown. To assess NCX3 role in cerebral ischemia, we exposed ncx3−/− mice to transient middle cerebral artery occlusion followed by reperfusion. In addition, to evaluate the effect of ncx3 ablation on neuronal survival, organotypic hippocampal cultures and primary cortical neurons from ncx3−/− mice were subjected to oxygen glucose deprivation (OGD) plus reoxygenation. Here we report that ncx3 gene suppression leads to a worsening of brain damage after focal ischemia and to a massive neuronal death in all the hippocampal fields of organotypic cultures as well as in cortical neurons from ncx3−/− mice exposed to OGD plus reoxygenation. In addition, in ncx3−/− cortical neurons exposed to hypoxia, NCX currents, recorded in the reverse mode of operation, were significantly lower than those detected in ncx3+/+. From these results, NCX3 protein emerges as a new molecular target that may have a potential therapeutic value in modulating cerebral ischemia.