RUOLO DELLO SCAMBIATORE SODIO/CALCIO E DELLE SUE ISOFORME IN UN MODELLO ANIMALE DI ISCHEMIA CEREBRALE FOCALE

In the Central Nervous System (CNS), the Na+/Ca2+ exchanger plays a fundamental role in controlling the changes in the intracellular concentrations of Na+ and Ca2+ ions. Three different Na+/Ca2+ exchanger isoforms NCX1, NCX2, NCX3 are differentially expressed in the CNS [1], [2]. The aim of the present study was to investigate the role of NCX1, NCX2, NCX3 isoforms in cerebral ischemia induced by permanent Middle Cerebral Artery Occlusion (pMCAO). NCX1, NCX2, NCX3 mRNA expression determined by RT-PCR was examined in the ipsilateral area surrounding the ischemic core and in the hippocampus at 3, 6, 9 and 72 hrs after pMCAO. The results, obtained in 200 SD male rats, showed that NCX1 and NCX3 mRNA transcripts decreased in the area surrounding the ischemic core compared to the levels obtained in the corresponding areas of sham-operated controls. The decrease was 60% for NCX1 mRNA transcripts and 50% for those of NCX3. By contrast NCX2 and NCX3 mRNA levels increased in the hippocampus ipsilateral to the lesion. The percent of increase was 100% for NCX2 mRNA levels and 250% for those of NCX3. In agreement with the expression of NCX transcripts after pMCAO, the inhibition of the three NCX different isoforms by the specific antisense oligonucleotides-oligos AS1, AS2 and AS3 caused a different effect on the extension of the infarctual volume. In particular, intracerebroventricular infusion of AS1 and AS3 induced a 44% increase of the infarctual volume, whereas AS2 did not exert any effect. These results suggest that the three NCX isoforms present in the CNS could play a differential role in cerebral ischemia. [1] Canitano A., Papa M., Boscia F., Castaldo P., Sellitti S., Taglialatela M., and Annunziato L. (2002) Ann. N.Y. Acad. Sci. 976: 394-404. [2] Papa M., Canitano A., Boscia F., Castaldo P., Sellitti S., Porzig H., Taglialatela M., and Annunziato L. (2003) The J Comp Neurol 467: 1-18