title: Postconditioning mitigates cell death following oxygen and glucose deprivation in PC12 cells and forebrain reperfusion injury in rats.
abstract: Postconditioning mitigates ischemia-induced cellular damage via a modified reperfusion procedure. Mitochondrial permeability transition (MPT) is an important pathophysiological change in reperfusion injury. This study explores the role of MPT modulation underlying hypoxic postconditioning (HPoC) in PC12 cells and studies the neuroprotective effects of ischemic postconditioning (IPoC) on rats. Oxygen-glucose deprivation (OGD) was performed for 10 hr on PC12 cells. HPoC was induced by three cycles of 10-min reoxygenation/10-min rehypoxia after OGD. The MPT inhibitor N-methyl-4-isoleucine cyclosporine (NIM811) and the MPT inducer carboxyatractyloside (CATR) were administered to selective groups before OGD. Cellular death was evaluated by flow cytometry and Western blot analysis. JC-1 fluorescence signal was used to estimate the mitochondrial membrane potential (△Ψm ). Transient global cerebral ischemia (tGCI) was induced via the two-vessel occlusion and hypotension method in male Sprague Dawley rats. IPoC was induced by three cycles of 10-sec reperfusion/10-sec reocclusion after index ischemia. HPoC and NIM811 administration attenuated cell death, cytochrome c release, and caspase-3 activity and maintained △Ψm of PC12 cells after OGD. The addition of CATR negated the protection conferred by HPoC. IPoC reduced neuronal degeneration and cytochrome c release and cleaved caspase-9 expression of hippocampal CA1 neurons in rats after tGCI. HPoC protected PC12 cells against OGD by modulating the MPT. IPoC attenuated degeneration of hippocampal neurons after cerebral ischemia.
authors.affiliation: Department of Anatomy and Cell Biology, Medical College, National Taiwan University, Taipei, Taiwan.
authors.forename: Han-Chen
authors.initials: HC
authors.lastname: Lin
authors.forename: Purnima
authors.initials: P
authors.lastname: Narasimhan
authors.forename: Shin-Yun
authors.initials: SY
authors.lastname: Liu
authors.forename: Pak H
authors.initials: PH
authors.lastname: Chan
authors.forename: I-Rue
authors.initials: IR
authors.lastname: Lai
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005452:Fluoresceins; D005562:Formazans; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology; D057775:Ischemic Postconditioning; D008297:Male; D053078:Membrane Potential, Mitochondrial; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology*; D013778:Tetrazolium Salts
chemical_list: D005452:Fluoresceins; D005562:Formazans; D013778:Tetrazolium Salts; C435731:fluoro jade; C079782:MTT formazan; D045304:Cytochromes c; D053148:Caspase 3; D005947:Glucose; D010100:Oxygen
keywords: hippocampus; hypoxia; mitochondrial permeability transition; neuronal ischemia; oxygen-glucose deprivation; postconditioning