Abstract TP109: Quantitative Gait Analysis Demonstrates Significant Changes in Motor Function Post-ischemic Stroke and Simulated Intraparenchymal Therapeutic Delivery in a Porcine Model

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Severity of stroke and subsequent recovery can be measured through gait changes of affected individuals. Recent failures of therapies tested in rodents to support safety and efficacy in human clinical trials has led to the development of a novel porcine ischemic stroke model with more comparable brain anatomy and physiology. Assessment of motor function changes is essential for determining the feasibility of the pig stroke model, the effect of therapies and the potential effects of modes of therapeutic delivery such as intraparenchymal injection. We hypothesized permanent occlusion of the middle cerebral artery (MCA) and the intraparenchymal injection process would lead to significant alterations in motor functions such as increased stride duration and decreased two limb support and stride swing time. Gait data was collected on 3 adult male Landrace pigs at 3 pre-stroke time points. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) and pigs were evaluated at 1, 3 and 5 days post-stroke. Stride duration increased by >50% and percent swing time and percent two limb support decreased by >30% 1 day post-stroke. Increased stride duration and decreased relative swing time and two limb support phase persisted 3 and 5 days post-stroke. At 5 days post-stroke, pigs received PBS intraparenchymal injections and were recorded at 1 and 3 days and 1, 2, 4, 6, 9 and 12 weeks post-injection. Stride duration significantly increased between 5 days post-stroke and 1 day post-injection demonstrating injection had a negative effect on motor function. All other parameters showed no significant changes between 5 days post-stroke and 1 day post-injection. Despite significant changes in gait parameters at early time points post-stroke, by 12 weeks post-injection, pigs showed spontaneous recovery with no detectable changes in motor function as compared to pre-stoke time points. Collectively, these results demonstrate MCAO stroke and intraparenchymal injection led to gait impairments and show that gait analysis is a highly sensitive method to detect changes in motor function.

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