title: Connexin-43 hemichannels contribute to the propagation of μ-calpain-mediated neuronal death in a cortical ablation injury model.
abstract: We investigated the role of the astrocytic and neuronal hemichannels (HCs) in the spread of cortical neuronal death in a rat cortical injury model. Over time (by 6 h), propidium iodide (PI)-positive cells with labeling either with anti-neuron specific enolase or anti-parvalbumin (indicating GABAnergic interneurons) antibody spread in the deep cortical layers adjacent to the injury and co-localized with activated μ-calpain. Connexin (Cx)-43, glial fibrillary acidic protein (GFAP), activated μ-calpain and α-fodrin breakdown product (FBP) increased post-injury, peaking at 1 h, in the injury and adjacent areas. GFAP-Cx43-positive reactivated astrocytes exhibited similar distribution to the dead neurons. Cx43 and Cx36 primarily comprise HCs in the astrocyte and neuron, respectively. Ethidium bromide (EtBr) uptake was enhanced post-injury, and confirmed in the Cx43- and Cx36-positive cells. A Cx43-HC inhibitor Gap26 prevented the opening of the Cx43-HC and Cx36-HC, μ-calpain activation, α-fodrin proteolysis and death in the deep cortical neurons. Collectively, opening of the astrocytic Cx43-HC and neuronal Cx36-HC would induce the regional spread of cortical neuronal death through μ-calpain activation in the rat brain injury model.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kaori
authors.initials: K
authors.lastname: Shintani-Ishida
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002154:Calpain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D013049:Spectrin
chemical_list: D002154:Calpain; D002352:Carrier Proteins; D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D010455:Peptides; D013049:Spectrin; C514423:Gap 26 peptide; C580592:Gja1 protein, rat; C449002:mu-calpain