Browsing by Author "Ma, Evelyn M."

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    Involvement of pannexin-1 channels and the mitochondria permeability transition in ischemic neuronal death
    (2011) Ma, Evelyn M.; Thompson, Roger John
    Stroke, the interruption in blood flow to the brain, initiates a neurotoxic cascade that leads to cell death. The aim of this thesis was to determine the role of Panx 1 channels in the neurotoxic cascade induced by ischemia in the rat hippocampus. Two approaches were taken: (1) the link between Panxl opening and MPT activation was investigated by monitoring dye efflux using live cell fluorescence microscopy, (2) the involvement of Panxl in cell death was determined by Western blot analysis of cleaved cytoskeletal protein, a-fodrin. Ischemia induced opening of the MPT was prevented by blocking calcium influx through Panxl channels. Panxl opening during ischemia also induced calpain proteolysis. This cleavage was prevented when either Panxl or the MPT were blocked. Therefore, opening of Panxl during ischemia activates the MPT and calpain proteases via calcium influx, indicating that Panxl channels induce neuronal death through mitochondria dysfunction and degradation of the cytoskeleton.