Abstract
The Stroke Therapy Academic Industry Roundtable (STAIR) has recommended that novel therapeutics be tested in a large animal model with similar anatomy and physiology to humans. The pig is an attractive model due to similarities in brain size, organization, and composition relative to humans. However, multiple pig breeds have been used to study ischemic stroke with potentially differing cerebral anatomy, architecture and, consequently, ischemic stroke pathologies. The objective of this study was to characterize brain anatomy and assess spatiotemporal gait parameters in Yucatan (YC) and Landrace (LR) pigs pre- and post-stroke using magnetic resonance imaging (MRI) and gait analysis, respectively. Ischemic stroke was induced via permanent middle cerebral artery occlusion (MCAO). MRI was performed pre-stroke and 1-day post-stroke. Structural and diffusion-tensor sequences were performed at both timepoints and analyzed for cerebral characteristics, lesion diffusivity, and white matter changes. Spatiotemporal and relative pressure gait measurements were collected pre- and 2-days post-stroke to characterize and compare acute functional deficits. The results from this study demonstrated that YC and LR pigs exhibit differences in gross brain anatomy and gait patterns pre-stroke with MRI and gait analysis showing statistical differences in the majority of parameters. However, stroke pathologies in YC and LR pigs were highly comparable post-stroke for most evaluated MRI parameters, including lesion volume and diffusivity, hemisphere swelling, ventricle compression, caudal transtentorial and foramen magnum herniation, showing no statistical difference between the breeds. In addition, post-stroke changes in velocity, cycle time, swing percent, cadence, and mean hoof pressure showed no statistical difference between the breeds. These results indicate significant differences between pig breeds in brain size, anatomy, and motor function pre-stroke, yet both demonstrate comparable brain pathophysiology and motor outcomes post-stroke. The conclusions of this study suggest pigs of these different breeds generally show a similar ischemic stroke response and findings can be compared across porcine stroke studies that use different breeds.
Highlights
Stroke is one of the leading causes of disability and death with recent studies indicating there are 33 million stroke survivors and 5.9 million stroke-related deaths across nearly 300 countries every year [1,2,3]
No significant differences were observed in mean Fractional anisotropy (FA) values between YC (Figure 2A) and LR (Figure 2B) pigs prestroke for major white matter tracts including the left internal capsule (LIC), right internal capsule (RIC), and corpus collosum (CC; Figure 2C)
We investigated breed-based differences between YC biomedical pigs and LR commercial pigs before and after ischemic stroke using neuroimaging and motor function analyses
Summary
Stroke is one of the leading causes of disability and death with recent studies indicating there are 33 million stroke survivors and 5.9 million stroke-related deaths across nearly 300 countries every year [1,2,3]. Ischemic stroke survivors often suffer from severe cognitive, behavioral, and motor function deficits that drastically impact their quality of life and frequently require longterm rehabilitation and medical care [3]. The use of large animal models is not yet widely utilized due to challenges associated with specialized maintenance requirements and large interdisciplinary research teams [10]. Despite these challenges, the pig ischemic stroke model has a number of unique advantages in brain anatomy and physiology that make it an attractive model to study stroke pathophysiology and test novel therapeutics [11,12,13,14,15]
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