Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia.
Gap junctions assemble astrocytes into syncytia, allowing exchange of metabolites, catabolites, and second-messenger molecules. Connexin43 is the predominant connexin of astrocytic gap junctions. The distribution of gap junction protein connexin43 was analyzed in different subfields of the hippocampal formation as a function of time after transient forebrain ischemia. One decisive key step in understanding why an ischemic insult gradually expands may be to establish how gap junction channels permit dying cells in the ischemic focus to communicate, in particular, with viable cells. The role of gap junctional intercellular communication in the hippocampus under ischemic conditions could be decisive for cell death propagation. We found that the vulnerable CA1/CA2 subfields have a higher density of gap junctions than the resistant CA3/CA4 areas, that changes in the distribution of connexin43 immunoreactivity may correlate with the phenomenon of selective vulnerability, and that inhibition of astrocytic gap junction permeability by octanol restricts the flow of undesirable neurotoxins that could potentially exacerbate neuronal damage. This provides a novel perspective for analysis of the pathophysiology of cerebral ischemia.
Rami
A
A
Anatomisches Institut III, Dr. Senckenbergische Anatomie, Universitätsklinikum, Theodor-Stern-Kai 7, Frankfurt, 60590, FRG. Rami@em.uni-frankfurt.de
Volkmann
T
T
Winckler
J
J
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death; D018031:Connexin 43 / Q000032:analysis; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006221:Halothane / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D000442:Octanols / Q000494:pharmacology*; D009829:Oleic Acids / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D000442:Octanols; D009829:Oleic Acids; C029407:oleylamide; D006221:Halothane