Item – Theses Canada

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OCLC number
471036770
Link(s) to full text
LAC copy
LAC copy
Author
Scott, Courtney Anne,1983-
Title
Evaluation of the role of excitotoxicity in an experimental model of rabies in mice.
Degree
M. Sc. -- Queen's University, 2007
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2008]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
Rabies is one of the most lethal of all infectious diseases. It is thought that the severe clinical illness and fatal outcome is due to neuronal dysfunction, rather than neuronal death, because only mild histopathological lesions are found under natural conditions. In this study, we examine the hypothesis that excitotoxicity may serve as a basis for neuronal dysfunction in rabies virus infection. The administration of ketamine (60mg/kg intraperitoneally q12h) to adult ICR mice inoculated intracerebrally or in the hindlimb footpad with the challenge virus standard (CVS-11) strain of rabies virus did not result in reduced mortality or the amelioration of clinical neurological disease compared to the administration of vehicle. Therapy with ketamine did not reduce the number of infected neurons in various brain regions or the severity of apoptotic changes in the brains of intracerebrally-inoculated mice. Transgenic mice expressing yellow fluorescent protein (YFP) in neurons and inoculated in the hindlimb footpad with CVS displayed beading and fragmentation of the dendrites and axons of layer V pyramidal neurons in the cerebral cortex, cerebellar mossy fibers and axon tracts in the brainstem, whereas neuronal processes in the hippocampus and perikarya showed relatively few changes under fluorescent microscopy. These morphological abnormalities differ from the beading observed in excitotoxicity, which is particularly severe in the hippocampus and is characterized by selective dendritic injury. Toluidine blue staining of plastic embedded tissues revealed vacuoles within the perikarya and proximal dendrites of pyramidal neurons in the cerebral cortex and hippocampus of YFP mice, and larger vacuolation within the neuropil of the cerebral cortex. Ultrastructurally, the neuropil vacuolation primarily represented swollen neuronal processes and pre-synaptic nerve endings, while the cytoplasmic vacuoles corresponded with swollen mitochondria. Mitochondrial swelling is a typical feature of excitotoxic injury, but excitotoxicity is also associated with microtubule fragmentation, which was not observed in the present study. Overall, we feel that the evidence does not support an important role for excitotoxicity in experimental rabies. Furthermore, the structural abnormalities observed in YFP mice support a role for severe neuronal injury without prominent neuronal death in rabies virus infection, as opposed to neuronal dysfunction without morphological changes.
ISBN
9780494302453
0494302453