Blockade of Gap Junctions In Vivo Provides Neuroprotection After Perinatal Global Ischemia
- 1 October 2005
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 36 (10), 2232-2237
- https://doi.org/10.1161/01.str.0000182239.75969.d8
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.This publication has 21 references indexed in Scilit:
- Carbenoxolone Inhibition of Voltage-Gated Ca Channels and Synaptic Transmission in the RetinaJournal of Neurophysiology, 2004
- Gap Junctions Mediate Bystander Cell Death in Developing RetinaJournal of Neuroscience, 2003
- Gap Junctions and Neuronal Injury: Protectants or Executioners?The Neuroscientist, 2003
- Ischemia-Induced Brain Damage Depends on Specific Gap-Junctional CouplingJournal of Cerebral Blood Flow & Metabolism, 2002
- Temporal expression of neuronal connexins during hippocampal ontogenyBrain Research Reviews, 2000
- Alterations in the neural growth hormone axis following hypoxic–ischemic brain injuryMolecular Brain Research, 1999
- Effective reduction of infarct volume by gap junction blockade in a rodent model of strokeJournal of Neurosurgery, 1997
- Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapyJournal of Neurosurgery, 1996
- The influence of immaturity on hypoxic‐ischemic brain damage in the ratAnnals of Neurology, 1981
- Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in ratsJournal of Comparative Neurology, 1965