| The neuronal response to injury / | |
Abstract/OtherAbstract
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This work is a study of in vivo neuronal injury of the central nervous system (CNS). It investigates the neuropathological sequelae and mechanisms involved in both the response to and recovery from CNS injury. Two animal models are used: traumatic brain injury (TBI) and seizure, both performed in the rat. Using the cortical impact injury model of TBI in the rat, the pathophysiological results of injury and the induction of protracted apoptotic cell death in specific brain regions of traumatically injured animals are addressed. Following TBI, silver stain histological analysis detected the appearance of dystrophic neurons in the hippocampus, cortex, amygdala, thalamus, and hypothalamus. Dystrophic cells were detected for at least 2 weeks following injury, and their location correlated with regions of cell loss. These regions have been shown to be functionally related to the post-injury behavioural deficits observed in this paradigm. These dystrophic cells were demonstrated to be apoptotic by morphological examination using electron microscopy, gel electrophoresis and in situ detection of DNA fragmentation, and nuclear condensation detected using Hoechst stain. Recovery from the behavioural deficits caused by the injury is accompanied by biochemical changes that suggest that regeneration of the affected neuronal systems is occurring. To address this aspect of the neuronal response to injury and to investigate a possible biochemical mechanism, netrin induction following pilocarpine-induced seizure (a model of human temporal lobe epilepsy) was investigated. First, netrin, an embryonically-expressed axonal guidance molecule was shown to be expressed in the adult rat brain, and the distribution of netrin protein and mRNA was mapped. Then, by sampling tissue at successive time points following pilocarpine-induced seizure in rats, netrin and the axon-attracting netrin receptor DCC were demonstrated to be induced in brain regions associated with neuronal cell damage and loss, and subsequent axonal sprouting. Together these data demonstrate a role for the activation of apoptotic mechanisms in the neuronal cell loss that occurs following injury and suggest a role for the upregulation of netrin protein in the subsequent regeneration and recovery of the central nervous system following injury. |
Authors
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Colicos, Michael Adrian. |
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Contributors
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Kennedy, T. E. (advisor) |
Publication Detail
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Publisher : McGill University Type : Electronic Thesis or Dissertation Format : application/pdf |
Date Detail
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1999 |
Subject
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Biology, Molecular., Biology, Neuroscience., Biology, Cell. |
Coverage
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- |
Relation
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alephsysno: 001681965, proquestno: NQ55314 |
Source
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- |
Copyright Information
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© Michael Adrian Colicos, 1999 |
Other Details
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Languages : en |
Export Citation
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