Gait analysis in a pre- and post-ischemic stroke biomedical pig model

Duberstein, K.J.; Platt, Simon R.; Holmes, Shannon P.; Dove, C. R.; Howerth, Elizabeth W.; Kent, Marc; Stice, Steven L.; Hill, W. David; Hess, David C.; West, Franklin D.

doi:10.1016/j.physbeh.2013.11.004

Cited by 45 publications

(35 citation statements)

References 24 publications

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“…Symmetry is generally assumed to be a characteristic feature of normal and stable locomotion (Oosterlinck et al, 2010;Herzog et al, 1989;Jeleńet al, 2008;Budsberg et al, 1987;Besancon et al, 2004;Duberstein et al, 2014). Results obtained by Meijer et al (2014) indicate a very high degree of symmetry in healthy adult pigs.…”

Section: Does Intralimb Coordination Differ As a Function Of Body Build?mentioning

confidence: 99%

How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets

Hole

Goyens

Prims

et al. 2017

Journal of Experimental Biology

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Locomotion is one of the most important ecological functions in animals. Precocial animals, such as pigs, are capable of independent locomotion shortly after birth. This raises the question whether coordinated movement patterns and the underlying muscular control in these animals is fully innate or whether there still exists a rapid maturation. We addressed this question by studying gait development in neonatal pigs through the analysis of spatio-temporal gait characteristics during locomotion at self-selected speed. To this end, we made video recordings of piglets walking along a corridor at several time points (from 0 h to 96 h). After digitization of the footfalls, we analysed self-selected speed and spatio-temporal characteristics (e.g. stride and step lengths, stride frequency and duty factor) to study dynamic similarity, intralimb coordination and interlimb coordination. To assess the variability of the gait pattern, left-right asymmetry was studied. To distinguish neuromotor maturation from effects caused by growth, both absolute and normalized data (according to the dynamic similarity concept) were included in the analysis. All normalized spatiotemporal variables reached stable values within 4 h of birth, with most of them showing little change after the age of 2 h. Most asymmetry indices showed stable values, hovering around 10%, within 8 h of birth. These results indicate that coordinated movement patterns are not entirely innate, but that a rapid neuromotor maturation, potentially also the result of the rearrangement or recombination of existing motor modules, takes place in these precocial animals.

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Section: Does Intralimb Coordination Differ As a Function Of Body Build?mentioning

confidence: 99%

How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets

Hole

Goyens

Prims

et al. 2017

Journal of Experimental Biology

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“…Here, this model has been tested in fat-fed Ossabaw to test nitrite delivery on angiogenesis and coronary vasoreactivity in these animals 21, 22 . Finally the quantification of gait disturbance in this model was under-developed and can be better analyzed with existing technology 46 .…”

Section: Discussionmentioning

confidence: 99%

An endovascular model of ischemic myopathy from peripheral arterial disease

Long

Timmins

Koutakis

et al. 2017

Journal of Vascular Surgery

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Objective Peripheral arterial disease (PAD) is a significant age-related medical condition with limited pharmacologic options. Severe PAD, termed critical limb ischemia (CLI), can lead to amputation. Skeletal muscle is the end organ most affected by PAD leading to ischemic myopathy and patient debility. Currently, there are not any therapeutics to treat ischemic myopathy, and proposed biologic agents have not been optimized due to a lack of pre-clinical models of PAD. Since a large animal model of ischemic myopathy may be useful in defining the optimal dosing and delivery regimens, the objective was to create and characterize a swine model of ischemic myopathy that mimics patients with severe PAD. Methods Yorkshire swine (N = 8) underwent acute right hindlimb ischemia via endovascular occlusion of the external iliac artery. The effect of ischemia on limb function, perfusion, and the degree of ischemic myopathy was quantified by weekly gait analysis, arteriography, hindlimb blood pressures, femoral artery duplex ultrasounds, and histologic examination. Animals were terminated at 5 (N = 5) and 6 (N = 3) weeks post-operatively. Ossabaw swine (N = 8) fed a high fat diet were utilized as a model of metabolic syndrome for comparison of arteriogenic recovery and validation of ischemic myopathy. Results There was persistent ischemia in the right hindlimb and occlusion pressures were significantly depressed compared to the untreated left hindlimb out to 6 weeks (SBP 31±21 versus 83±15, respectively; P=0.0007). The blood pressure reduction resulted in a significant increase of ischemic myopathy in the gastrocnemius muscle in the treated limb. Gait analysis revealed a functional deficit of the right hindlimb immediately post-occlusion that improved rapidly over the first 2 weeks. Peak systolic velocity values in the right common femoral artery were severely diminished throughout the entire study (P<0.001), and the hemodynamic environment post-occlusion was characterized by low and oscillatory wall shear stress. Finally, the internal iliac artery on the side of the ischemic limb underwent significant arteriogenic remodeling (1.8x baseline) in the Yorkshire, but not the Ossabaw swine model. Conclusions This model utilizes endovascular technology to produce the first durable large animal model of ischemic myopathy. Acutely (first 2 weeks) this model is associated with impaired gait but no tissue loss. Chronically (2-6 weeks), this model delivers persistent ischemia resulting in ischemic myopathy similar to that seen in PAD patients. This model may be of use for testing novel therapeutics including biologic therapies for promoting neovascularization and arteriogenesis.

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“…Animals also showed functional deficits including limb weakness and impaired ambulation. Previous work by our group showed that a novel gait analysis system could be utilized for more refined and quantitative detection of changes in gait in biomedical pigs, which should be employed in future studies [43]. …”

Section: Discussionmentioning

confidence: 99%

Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model

Platt

Holmes

Howerth

et al. 2014

Exp & Trans Stroke Med

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BackgroundEfforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.MethodsEleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey’s Pair-Wise comparisons.ResultsMRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.ConclusionsThe MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

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Gait analysis in a pre- and post-ischemic stroke biomedical pig model

Cited by 45 publications

References 24 publications

How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets

How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets

An endovascular model of ischemic myopathy from peripheral arterial disease

Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model

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