title: Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Mara H
authors.initials: MH
authors.lastname: de Pina-Benabou
authors.forename: Vanessa
authors.initials: V
authors.lastname: Szostak
authors.forename: Andreas
authors.initials: A
authors.lastname: Kyrozis
authors.forename: David
authors.initials: D
authors.lastname: Rempe
authors.forename: Daniela
authors.initials: D
authors.lastname: Uziel
authors.forename: Marcia
authors.initials: M
authors.lastname: Urban-Maldonado
authors.forename: Salomon
authors.initials: S
authors.lastname: Benabou
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: Renato
authors.initials: R
authors.lastname: Rozental
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D017209:Apoptosis; D001921:Brain / Q000196:embryology*; D002229:Carbenoxolone / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication; D017630:Connexins / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004195:Disease Models, Animal; D004594:Electrophysiology; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011419:Propidium / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D017630:Connexins; D018696:Neuroprotective Agents; D009707:Nucleosomes; D012333:RNA, Messenger; D011419:Propidium; D004247:DNA; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose; D002229:Carbenoxolone; D010100:Oxygen