This thesis investigates the behavioural and anatomical correlates of recovery from motor cortex damage in rats. The effectiveness of behavioural, pharmacological, and regenerative treatments was investigated using models of focal stroke. Chronic bilateral motor deficits were found after motor cortex damage induced by various methods. These behavioural deficits were similar in severity and duration although they were correlated with different patterns of reorganization seen in Golgi-stained tissue. Animals with motor cortex injury benefited from postinjury olfactory stimulation, chronic administration of nicotine, and infusions of epidermal growth factor followed by erythroprotein. Different mechanisms of plasticity in remaining cortical circuits are discussed as possible candidates responsible for the behavioural improvement. The current thesis expands the current knowledge of the effects of adult cortical damage to ares critical to motor control. It may also stimulate research on therapies and possible mechanisms that might enhance recovery after stroke. / xviii, 299 leaves : ill. (some col.) ; 29 cm.

Stroke is the third leading cause of death and survivors suffer motor impairments. The rodent sensorimotor system is similar to the human's, making rodents a good model to study the effects of stroke. Transgenic technology makes the mouse a desirable stroke model, however, there are few behavioural tests to assess behavioural outcome. This thesis evaluates mice subjected to permanent or temporary occlusion focal motor cortex strokes in a skilled reaching task. The first experiment documents changes in skilled movements in mice with a permanent occlusion focal motor cortex stroke. The second experiment is identical but uses a temporary occlusion focal motor cortex stroke. The third experiment compares the two strokes. The results indicate permanent occlusion mice suffer great impairments, and a larger injury, than temporarily occluded animals. The mice with the largest insults were most impaired. Mice make an excellent behavioural and genetic model for studying motor system stroke. / viii, 115 leaves : ill. ; 29 cm.

The effects of pre-stroke exercise and levesl of brain-derived neurotrophic factor (BDNF) on behavioural and functional recovery were examined following focal cortical ischemic infarct. Intracortical microstimulation (ICMS) was used to derive topographical maps of forelimb representations within the motor cortex and ischemia was induced via bipolar coagulation of surface vasculature. One month of excerise prior to ischemia significantly increased the amount of peri-infarct movement represnetations and initiates vascular changes within motor cortex. Further, this exercise-induced preservation of peri-infarct movement representations is associated with behavioural recovery and is dependent on BDNF levels in the motor cortex. These results provide further support for the idea that endurance exercise prior to stroke may enhance functional and behavioural recovery. / 140 leaves : ill. (some col.) ; 29 cm.

The purpose of this thesis is to describe the organization of the movements of skilled reaching. Our knowledge of reaching behaviour has been limited to an understanding of specific actions. Results from this thesis describe how reaching is the product of interactions of various parameters that assemble in an integrative way in ontogeny, yet can become dismantled on one level, or generally, throughout multiple levels of what constitutes the behaviour after stroke in adults. These findings demonstrate that skilled reaching constitutes motor parameters that may not be visible in a healthy adult, but that function through development, and by inhibitory systems in adults, to create a smooth and finely articulated action. An examination of the movement patterns of reaching within the full context of the behaviour can be applied to therapeutic strategies for motor disorders and, most importantly, deepen our understanding of the relations between reaching and cognition. / xiii, 254 leaves : ill. (some col.) ; 29 cm

Stroke is one of the most common, and damaging, neurological afflictions. Stroke causes widespread and variable chronic effects, due to the limited regenerative ability of the adult brain. Altered gene expression induces neuronal changes necessary for plasticity-dependent recovery, effects which can be enhanced by growth hormone-based pharmaceuticals. These processes are driven by alterations in the informational capacity of the genome – changes driven by epigenetic regulators. Following experimental strokes, and treatment with EGF and EPO, this study shows that two epigenetic regulatory mechanisms, DNA methylation and microRNA regulation, are significantly altered, both in treated and untreated animals. Specifically, treatment induces a net global suppression of miRNA activity, which appears to modify the physical behaviour of neurons in domains ranging from plasticity and memory formation, growth and replication, and potentially even to neurological disease signalling. The confirmation of epigenetic alterations following a stroke indicates a future role for epigenetic neuro-pharmacology in stroke management. / x, [99] leaves : ill. (some col.) ; 29 cm

Stroke remains a leading cause of disability in the western world, with symptoms ranging in severity from mild congnitive or motor impairments, to severe impairments in both cognitive and motor domains. Despite ongoing research aimed at helping stroke patients the disease cannot be prevented or cured, therefore a large body of research has been aimed at identifying effective rehabilitative strategies. Based on our understanding of normal brain function, and the meachanisms mediating the limited spontaneous recovery that is observed following injury, factors that promote brain plasticity are likely to be effective treatments for stroke symptoms. The current thesis investigated three novel treatments (COX-2 inhibitor drug, vitamin supplement diet, and social experience) in a rat model of focal ischemia in the motor cortex. All three treatments have been previously shown to alter plasticity in the normal brain, however the current experiments show that the treatments have differential effects following stroke. The COX-2 inhibitors provided limited improvement in functional performance, whereas the vitamin supplement treatment had no effect. Social experience on the other hand was found to block the usually observed spontaneous improvements following the stroke. These results suggest that factors that alter dendritic plasticity may in fact serve as effective stroke treatments depending on the site and the mechanisms whereby the plastic changes are induced. / ix, 149 leaves : ill. ; 29 cm.

Middle cerebral artery (MCA) stroke can produce chronic incapacitating motor impairments. Understanding the neural basis of the motor syndromes is complicated by the diversity of neural structures damaged but the problem can be addressed in laboratory rats by inducing selective infarcts. Nevertheless, the motor syndromes that ensue from stroke in rats remain poorly understood and undermine its potential as a model for clinical stroke. The objective of the present thesis was to document the skilled reaching impairments from neocortical and subcortical MCA infarcts in rats. In addition, the integrity of the motor system components spared by the infarct was assessed neurophysiologically and neuroanatomically. Characteristic reaching impairments emerged from each infarct but there were also some overlapping features that might be explained by neural dysfunction extending beyond the boundaries of the infarct. The present studies showed that the laboratory rat is an ideal animal model for studying stroke, which should be of interest to both clinical and research scientists studying stroke. / xiii, 345 leaves : ill. ; 29 cm. + 1 CD-ROM

This thesis examined how pharmacological treatment and cortical injury during development affects brain plasticity. Rats were given either a low dose of perinatal fluoxetine or a mild postnatal day 7 Hypoxic‐Ischemic (HI) injury, both, or neither. The functional outcome was assessed using a series of behavioral tasks and anatomical measures. To assess how HI affects the development of motor maps, forelimb motor maps were evoked at P19. The findings indicate that fluoxetine treatment or HI injury mostly negatively affected functional outcome. The combined treatment with fluoxetine and HI injury only interacted on a limited number of measures. There was no delay in the emergence of evoked motor movements, or change in map location in the HI animals. These results suggest that the pharmacological treatment and cortical injury described in this thesis may have different mechanisms whereby plastic changes are induced and the interaction between these two mechanisms is limited. / xii, 169 leaves : ill. ; 29 cm.

Stroke outcome is highly variable. Experiments in this thesis test the hypothesis that experience prior to a stroke is an important variable in the manifestation of stroke. Optokinetic tracking was used to evaluate the effects of visual cortex stroke and MCA occlusion in rats. Normal laboratory rats showed a small, but significant decrease in tracking thresholds following visual cortex stroke. Animals with developmental visuomotor experience or reach training experience in adulthood, however, had tracking thresholds which were substantially increased, and the effects of visual cortex strokes were greater. MCA occlusions did not affect tracking behaviour. These data indicate that specific experiences engage neural plasticity that can alter brain function. These changes can, in turn, affect the behavioural manifestation of a stroke. Understanding the effect that environmental experience has on stroke outcome promises to enable better characterization of strokes, and set appropriate behavioural baselines for the measurement of recovery of function. / vi, 135 p. : ill. ; 29 cm

Stress has been shown to exacerbate cell death and cognitive deficits after ischemic injury in rodents, however, little is known of the effects of stress on motor recovery. The objective of this present thesis is to examine the effects of chronic stress on skilled motor recovery after devascularization lesion in rats. It was found that pre-lesion stress induced the most behavioural impairments, while post-lesion stress exacerbated infarct volume. The effects of chronic multiple stress on skilled motor recovery after lesion was also examined. Chronic multiple stress did not modulate skilled motor recovery nor did it have any influence on infarct volume. Additionally, stress had effect on edema after devascularization lesion. The present thesis suggests that the time of exposure to chronic stress in respect to the ischemic lesion, in addition to the type of stress, will differentially affect recovery and compensation in rats. / xii, 122 leaves : ill. ; 29 cm.