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PMID: 16179575 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia.

Stroke ·Vol. 36 ·No. 10 ·2005-10-00 ·Pages 2232-7

de Pina-Benabou MH, Szostak V, Kyrozis A, Rempe D, Uziel D, Urban-Maldonado M, Benabou S, Spray DC, Federoff HJ, Stanton PK, Rozental R

Abstract

We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage. Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.

MeSH Terms

Animals Anti-Ulcer Agents/pharmacology Apoptosis Brain/embryology Carbenoxolone/pharmacology Caspase 3 Caspases/metabolism Cell Communication Connexins/metabolism DNA/chemistry Disease Models, Animal Electrophysiology Female Gap Junctions/metabolism Glucose/metabolism Hippocampus/metabolism,pathology Hypoxia/pathology Hypoxia-Ischemia, Brain/pathology Ischemia/pathology Male Mice Mice, Inbred C57BL Microscopy, Fluorescence Nerve Degeneration Neurons/metabolism Neuroprotective Agents/metabolism Nucleosomes/metabolism Oxygen/chemistry Polymerase Chain Reaction Propidium/pharmacology RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Time Factors

Chemicals

Anti-Ulcer Agents Connexins Neuroprotective Agents Nucleosomes RNA, Messenger Propidium DNA Casp3 protein, mouse Casp3 protein, rat Caspase 3 Caspases Glucose Carbenoxolone Oxygen

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

de Pina-Benabou Mara H

Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.

Szostak Vanessa

Kyrozis Andreas

Rempe David

Uziel Daniela

Urban-Maldonado Marcia

Benabou Salomon

Spray David C

Federoff Howard J

Stanton Patric K

Rozental Renato

Article Info

Journal

Stroke

Abbr.

Stroke

ISSN

1524-4628

DOI

10.1161/01.STR.0000182239.75969.d8

Published

2005-10-00

Epub

2005-00-22

Pages

2232-7

Language

English

Region

United States

NLM ID

0235266

Subset

Grants

NINDS NIH HHS · R01NS042152 · United States

NINDS NIH HHS · R21NS42916 · United States

External Links

PubMed source DOI: 10.1161/01.STR.0000182239.75969.d8 View journal details

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Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia.

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