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

77 Citations (Scopus)

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

Fingerprint

Bepridil
Sodium-Calcium Exchanger
Middle Cerebral Artery Infarction
Brain Ischemia
Facilitative Glucose Transport Proteins
Brain
Neuroglia
Tyrosine
Pharmacology
Neurons
Peptides

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats. / Pignataro, Giuseppe; Tortiglione, Anna; Scorziello, Antonella; Giaccio, Lucia; Secondo, Agnese; Severino, Beatrice; Santagada, Vincenzo; Caliendo, Giuseppe; Amoroso, Salvatore; Di Renzo, Gianfranco; Annunziato, Lucio.

In: Neuropharmacology, Vol. 46, No. 3, 03.2004, p. 439-448.

Research output: Contribution to journalArticle

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, vol. 46, no. 3, pp. 439-448. https://doi.org/10.1016/j.neuropharm.2003.09.015
Pignataro, Giuseppe ; Tortiglione, Anna ; Scorziello, Antonella ; Giaccio, Lucia ; Secondo, Agnese ; Severino, Beatrice ; Santagada, Vincenzo ; Caliendo, Giuseppe ; Amoroso, Salvatore ; Di Renzo, Gianfranco ; Annunziato, Lucio. / Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats. In: Neuropharmacology. 2004 ; Vol. 46, No. 3. pp. 439-448.
@article{58d78969aaa14cd98d309c285918e3b6,
title = "Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats",
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.",
keywords = "CB-DMB, Fe ion, Focal ischemia, Na/Ca exchanger, pMCAO, XIP",
author = "Giuseppe Pignataro and Anna Tortiglione and Antonella Scorziello and Lucia Giaccio and Agnese Secondo and Beatrice Severino and Vincenzo Santagada and Giuseppe Caliendo and Salvatore Amoroso and {Di Renzo}, Gianfranco and Lucio Annunziato",
year = "2004",
month = "3",
doi = "10.1016/j.neuropharm.2003.09.015",
language = "English",
volume = "46",
pages = "439--448",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Evidence for a protective role played by the Na+/Ca 2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats

AU - Pignataro, Giuseppe

AU - Tortiglione, Anna

AU - Scorziello, Antonella

AU - Giaccio, Lucia

AU - Secondo, Agnese

AU - Severino, Beatrice

AU - Santagada, Vincenzo

AU - Caliendo, Giuseppe

AU - Amoroso, Salvatore

AU - Di Renzo, Gianfranco

AU - Annunziato, Lucio

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

KW - CB-DMB

KW - Fe ion

KW - Focal ischemia

KW - Na/Ca exchanger

KW - pMCAO

KW - XIP

UR - http://www.scopus.com/inward/record.url?scp=10744221646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744221646&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2003.09.015

DO - 10.1016/j.neuropharm.2003.09.015

M3 - Article

C2 - 14975699

AN - SCOPUS:10744221646

VL - 46

SP - 439

EP - 448

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 3

ER -