Item – Theses Canada

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OCLC number
939202091
Author
Livingston-Thomas, Jessica M.,1982-
Title
Evaluation of a novel approach to promoting post ischemic recovery of upper extremity function in the rat.
Degree
Ph. D. -- University of Prince Edward Island, 2013
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2014]
©2013
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
<?Pub Inc> Following stroke, impairments in arm function are common motor deficits in survivors, affecting thousands of people each year. A useful technique used in clinical rehabilitation of patients with arm impairments is to force use of the impaired arm through constraint of the unaffected (or less affected) one. The success of this constraint induced movement therapy' (CIMT) is believed to be due to neuroplastic changes that take place on a cellular level in surviving brain tissue, however, little is understood about the mechanisms involved. Appropriate animal models are necessary to study how rehabilitation affects neuroplasticity. Previous literature has described several models of forced use following stroke in rats which have resulted in varying success. Animal stress and lack of behavioural pressure may have contributed to the inconsistency of prior forced use models. The purpose of the research presented in this thesis was to optimize a surgical model of post-ischemic upper extremity impairment, determine whether it would be possible to force use of the impaired forelimb using a novel appetitively motivated protocol, and then to investigate the effects of this novel model on markers of neuroplasticity. First, the endothelin-1 (ET-1) model of focal unilateral ischemia was optimized by attempting a previously unpublished protocol of injections along the motor cortex and to the striatum. Male Sprague Dawley rats were subjected to ET-1 or sham surgery. Ensuing forelimb functional deficits were measured using a battery of behavioural tests, which were compared to intact sham surgical control performance. The stroke model resulted in reliable and reproducible lesions to forelimb motor regions of the brain, and deficits that lasted up to the end of the 21 day study period in some tests. Next, this ET-1 stroke surgery was used to evaluate a novel form of forced use rehabilitation in which rats engaged the impaired limb to move voluntarily in commercial pet activity balls. Animals were subjected to ET-1 or sham surgery, and then received either rehabilitation or a control treatment. Behavioural tests revealed that animals receiving rehabilitation recovered to sham levels of performance sooner than animals receiving the control treatment. Stroke, but not rehabilitation, affected the proportion of cells expressing brain derived neurotrophic factor (BDNF) and the presence of doublecortin-positive neuroblasts, but had no effect on the expression of the growth inhibiting protein NOGOA. Finally, the novel forced use model was developed further to more closely resemble clinical CIMT with the addition of a task-specific reaching component. Animals were subjected to either ET-1 followed by rehabilitation, ET-1 followed by a control treatment, or sham surgery. Again, behavioural tests revealed that animals that had undergone ET-1 surgery had significant deficits that recovered sooner in the group that received rehabilitation. Rehabilitation did not affect the proportion of BDNFexpressing cells, but did appear to cause a shift in the cellular origin of the BDNF that was present. Further, rehabilitation resulted in more doublecortin-positive cells in the damaged hemisphere. This novel approach to rehabilitation represents a useful model of forced use therapy which results in accelerated functional recovery following ischemic injury. The mechanisms underlying this effect may be related to changes in BDNF expression and increased generation or survival of new born cells.
ISBN
9780499004598
0499004590