Factors Affecting Focal Cerebral Ischemic Infarction: Inferences from Experimental Modelling in Macaques and Murines

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Harrison, Kathleen
Surgery , Animal Models , Magnetic Resonance Imaging , Non Human Primates , Medical Operations , Anasthesia , Brain Injury , Focal Cerebral Ischemic Stroke
Stroke is a leading cause of morbidity and mortality in North America. There has been an evolution in treatment and assessment of ischemic stroke over the last 30 years, related to formation of hospital acute stroke teams that provide thrombolytic therapy and endovascular thrombectomy. A challenge in stroke treatment is rapid identification and diagnosis to guide treatment. For example, differentiating between hemorrhagic or ischemic infarction, two common ‘types’ of stroke, is important as each pathology has a different treatment course. These challenges result in approximately 80% of patients considered ineligible for acute therapy, and 50% of all stroke patients experiencing major morbidity or mortality. For ethical and practical reasons, study of prospective stroke treatments does not occur in humans. Scientists and researchers have historically turned to animals as a proxy for investigating mechanisms of stroke, effects of strokes in different brain areas, and to evaluate the efficacy of new therapies for stroke and in translational studies prior to human clinical trials. For such studies to be of assistance in understanding human stroke, the animal model should resemble the mechanisms and effects of strokes in humans as much as possible. Unfortunately, as will be demonstrated in this thesis, this assumption may not be fully met in most animal models, such as the commonly employed rodent model of stroke. For example, the vascular and brain tissues in chosen animal species may not respond to induced strokes in the same manner as in humans, such as: injury size, cerebral metabolism, cerebral vascularity and perfusion, and thresholds of cell death. These confounding variables, and various animal models of stroke, are discussed in the background of the thesis. As such, the internal validity of animal models, and the external validity of these models in the translation to human stroke is currently unknown.
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