Browsing by Author "Thompson, Roger John"

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    Activation of Epiplexus Cells by ATP
    (2013-01-25) Maslieieva, Valentyna; Thompson, Roger John
    Epiplexus cells represent a population of innate immune cells on the surface of the choroid plexus (CP) in the brain ventricles. I hypothesized that the epiplexus cells are involved in immune responses of the CP via sensitivity to immune mediators such as ATP. A novel technique for the isolation of live and intact rat CP was developed that allowed, for the first time, observation and quantification of physiological responses of epiplexus cells in situ. Bath application of ATP, as well as ADP or UTP, activated movement (chemokinesis) of epiplexus cells. This was not dependent upon P2X7 and P2X4 receptors, but may involve epiplexus cell P2X1, P2X5, and / or P2Y13 and P2Y2 receptors and epithelial cell pannexin-1. Therefore, epiplexus cells respond to the immune mediator, ATP, and may receive signals directly from the epithelium on which they reside to mediate localized immune responses in the ventricle.
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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.
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    The role of pannexin1 channels in seizure activity in vivo and in vitro
    (2012) Robinson, Jordan; Teskey, G. Campbell; Thompson, Roger John
    Pannexinl (Panx 1) is a large-pore channel present in the post-synaptic site that has been implicated in an in vitro model of seizure-like burst firing. However, the precise contribution of Panxl to seizure activity remains controversial, with many inconsistent findings. Furthermore, the contribution of Panxl to the development of ictogenic nervous tissue ('epileptogenesis') has not been investigated. The present experiments pursue three lines of research in an attempt to further characterize the role of Panxl in seizure and epileptogenesis. The contributions of Panxl to susceptibility to seizure, seizure severity and seizure duration were studied in vivo using both the pilocarpine model of seizure and status epilepticus, and the electrical kindling model of seizure and epileptogenesis. Further, the effect of Panx 1 block on the process of epileptogenesis itself in the electrical kindling model was examined. Finally, the role of Panxl in local excitability and short-term potentiation following epileptogenesis were studied using acute hippocampal slices obtained from kindled and sham kindled rats. A single early central infusion of Panxl blocker was sufficient to chronically attenuate epileptogenesis. Furthermore, Panxl block acutely decreased seizure severity and afterdischarge threshold in fully kindled animals in the electrical kindling model. Panxl block was also found to acutely decrease seizure severity and increase seizure latency, but not seizure duration in the pilocarpine model. Finally, Panxl block was also found to increase paired-pulse facilitation but not differentially between kindled and non-kindled tissue.