Magnetic Resonance Imaging and Gait Analysis Indicate Similar Outcomes Between Yucatan and Landrace Porcine Ischemic Stroke Models

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.

Fecal microbial transplantation limits neural injury severity and functional deficits in a pediatric piglet traumatic brain injury model

“…Recovery of gross and fine motor skills and motor coordination is often stated as a patient’s primary goal of TBI rehabilitation, yet severe TBI frequently results in long term gait impairment in children despite significant rehabilitation efforts ( Katz-Leurer et al, 2008 ; Prasad et al, 2017 ). Our study found TBI induced a significant decrease in step and stride length, consistent with gait changes in piglet ( Baker et al, 2019 ; Kinder et al, 2019b ; Sneed et al, 2020 ) and human ( Kuhtz-Buschbeck et al, 2003 ; Katz-Leurer et al, 2008 ) pediatric TBI populations. Additionally, we observed decreases in open field voluntary motor parameters including distance traveled time spent moving and exploratory behaviors, such as sniffing, following TBI.…”

“…Four-week-old castrated male crossbreed piglets (N = 18) were used as experimental animals in this study due to animal availability. Previous research from our lab indicated that crossbreed animals showed similar brain pathophysiology and motor outcomes following TBI as Yucatan biomedical pigs (Sneed et al, 2020). Additional castrated male piglets (N = 9) were kept from each litter as healthy fecal matter donor pigs.…”

Establishment of a reproducible and minimally invasive ischemic stroke model in swine

“…Significant differences in macroscopic brain anatomy have been recently reported between strains/breeds of swine ( 54 ), so we used pigs of different genetic backgrounds in an angiographic study to search for anatomical vascular differences that could provide feasible access of the catheters to the CW, either through the RM or the vertebral arteries. In compliance with the 3R strategy to “reduce, refine, and replace,” when possible, the same swine provided data for more than 1 of the following objectives: (a) the angiographic study, (b) the catheterization and crossing attempt through the RM, (c) the training of the occlusion/embolization of the left wing of the RM, and (d) the occlusion/embolization of the left wing of the RM + left ICA + left side of the CW.…”