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

Mara H. De Pina-Benabou, Vanessa Szostak, Andreas Kyrozis, David Rempe, Daniela Uziel, Marcia Urban-Maldonado, Salomon Benabou, David C. Spray, Howard J. Federoff, Patric K. Stanton, Renato Rozental

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Background and Purpose - We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). Methods - Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). Results - 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. Conclusions - Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.

Original languageEnglish (US)
Pages (from-to)2232-2237
Number of pages6
JournalStroke
Volume36
Issue number10
DOIs
StatePublished - Oct 2005

Fingerprint

Gap Junctions
Ischemia
Carbenoxolone
Oxygen
Glucose
Caspase 3
Brain
Molecular Biology
Cell Death
Fluorescence
Apoptosis
Neuroprotection
Hypoxia
Therapeutics

Keywords

  • Apoptosis
  • Carbenoxolene
  • Connexin
  • Gap junction
  • Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

De Pina-Benabou, M. H., Szostak, V., Kyrozis, A., Rempe, D., Uziel, D., Urban-Maldonado, M., ... Rozental, R. (2005). Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. Stroke, 36(10), 2232-2237. https://doi.org/10.1161/01.STR.0000182239.75969.d8

Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. / De Pina-Benabou, Mara H.; Szostak, Vanessa; Kyrozis, Andreas; Rempe, David; Uziel, Daniela; Urban-Maldonado, Marcia; Benabou, Salomon; Spray, David C.; Federoff, Howard J.; Stanton, Patric K.; Rozental, Renato.

In: Stroke, Vol. 36, No. 10, 10.2005, p. 2232-2237.

Research output: Contribution to journalArticle

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 2005, 'Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia', Stroke, vol. 36, no. 10, pp. 2232-2237. https://doi.org/10.1161/01.STR.0000182239.75969.d8
De Pina-Benabou MH, Szostak V, Kyrozis A, Rempe D, Uziel D, Urban-Maldonado M et al. Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. Stroke. 2005 Oct;36(10):2232-2237. https://doi.org/10.1161/01.STR.0000182239.75969.d8
De Pina-Benabou, Mara H. ; Szostak, Vanessa ; Kyrozis, Andreas ; Rempe, David ; Uziel, Daniela ; Urban-Maldonado, Marcia ; Benabou, Salomon ; Spray, David C. ; Federoff, Howard J. ; Stanton, Patric K. ; Rozental, Renato. / Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. In: Stroke. 2005 ; Vol. 36, No. 10. pp. 2232-2237.
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