Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats

Giuseppe Pignataro, Anna Tortiglione, Antonella Scorziello, Lucia Giaccio, Agnese Secondo, Beatrice Severino, Vincenzo Santagada, Giuseppe Caliendo, Salvatore Amoroso, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticle

Abstract

In the present paper, the role played by Na+/Ca2+ exchanger (NCX) in focal cerebral ischemia was investigated. To this aim, permanent middle cerebral artery occlusion (pMCAO) was performed in male rats. The effects on the infarct volume of some inhibitors, such as tyrosine-6 glycosylated form of the exchanger inhibitory peptide (GLU-XIP), benzamil derivative (CB-DMB) and diarylaminopropylamine derivative (bepridil), and of the NCX activator, FeCl3, were examined. FeCl3, CB-DMB, bepridil and GLU-XIP, a modified peptide synthesized in our laboratory in order to facilitate its entrance into the cells through the glucose transporter, were intracerebroventricularly (icv) infused. FeCl3 (10 μg/kg) was able to reduce the extenson of brain infarct volume. This effect was counteracted by the concomitant icv administration of CB-DMB (120 μg/kg). All NCX inhibitors, GLU-XIP, CB-DMB and bepridil, caused a worsening of the brain infarct lesion. These results suggest that a stimulation of NCX activity may help neurons and glial cells that are not irreversibly damaged in the penumbral zone to survive, whereas its pharmacological blockade can compromise their survival.

Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalNeuropharmacology
Volume46
Issue number3
DOIs
Publication statusPublished - Mar 2004

Keywords

  • CB-DMB
  • Fe ion
  • Focal ischemia
  • Na/Ca exchanger
  • pMCAO
  • XIP

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Fingerprint Dive into the research topics of 'Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats'. Together they form a unique fingerprint.

  • Cite this

    Pignataro, G., Tortiglione, A., Scorziello, A., Giaccio, L., Secondo, A., Severino, B., Santagada, V., Caliendo, G., Amoroso, S., Di Renzo, G., & Annunziato, L. (2004). Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats. Neuropharmacology, 46(3), 439-448. https://doi.org/10.1016/j.neuropharm.2003.09.015