Porcine spinal cord injury model for translational research across multiple functional systems

Ahmed, Rakib Uddin; Knibbe, Chase A.; Wilkins, Felicia; Sherwood, Leslie C.; Howland, Dena R.; Boakye, Maxwell

doi:10.1016/j.expneurol.2022.114267

Cited by 10 publications

(12 citation statements)

References 108 publications

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“…A pig's spinal cord is large enough to allow the probes to be inserted and evaluated. This information will be useful for translating the information into the clinic with respect to patient care, monitoring, and management practices ( 63 ). With collecting more data, we should be able to integrate these clinical parameters so a scoring system can be achieved for predicting the prognosis.…”

Section: Discussionmentioning

confidence: 99%

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

Chen²,

Wang³

et al. 2023

Front. Neurol.

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IntroductionSpinal cord injury (SCI) is a devastating neurological disorder with an enormous impact on individual's life and society. A reliable and reproducible animal model of SCI is crucial to have a deeper understanding of SCI. We have developed a large-animal model of spinal cord compression injury (SCI) with integration of multiple prognostic factors that would have applications in humans.MethodsFourteen human-like sized pigs underwent compression at T8 by implantation of an inflatable balloon catheter. In addition to basic neurophysiological recording of somatosensory and motor evoked potentials, we introduced spine-to-spine evoked spinal cord potentials (SP-EPs) by direct stimulation and measured them just above and below the affected segment. A novel intraspinal pressure monitoring technique was utilized to measure the actual pressure on the cord. The gait and spinal MRI findings were assessed in each animal postoperatively to quantify the severity of injury.ResultsWe found a strong negative correlation between the intensity of pressure applied to the spinal cord and the functional outcome (P < 0.0001). SP-EPs showed high sensitivity for real time monitoring of intraoperative cord damage. On MRI, the ratio of the high-intensity area to the cross-sectional of the cord was a good predictor of recovery (P < 0.0001).ConclusionOur balloon compression SCI model is reliable, predictable, and easy to implement. By integrating SP-EPs, cord pressure, and findings on MRI, we can build a real-time warning and prediction system for early detection of impending or iatrogenic SCI and improve outcomes.

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Section: Discussionmentioning

confidence: 99%

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

Chen²,

Wang³

et al. 2023

Front. Neurol.

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“…The porcine spinal cord is similar to that of humans, with comparable gray to white matter ratios, cortical structure, sacral enlargement, cord dimensions/structure/organization, and metabolic demands [ 40 , 41 , 42 , 43 , 44 , 45 ]. This porcine SCI model serves to assess critical GI parameters, a major comorbidity in SCI patients, compare to human functionality, and consider interventions to improve GI function.…”

Section: Introductionmentioning

confidence: 99%

SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model—A Preliminary Study

et al. 2023

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Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function.

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“…[2][3][4] Moreover, an interest in the large animal model is more closely aligned because of the similarity in size compared to the human spinal cord. 4,5 Advantages of this model include large cord size, cerebrospinal fluid/cord ratios, neuroanatomical similarity to the human spinal cord, and physiological similarities to humans. [6][7][8][9][10][11] The sizeable spinal canal and cord allow for the evaluation of advanced spinal cord imaging methods applicable to humans.…”

Section: Introductionmentioning

confidence: 99%

“…Many advanced neuroimaging studies have been performed in rodents. However, significant anatomical, functional, molecular, and pathological differences between rodent and human spinal cords have also been cited as possible reasons for the lack of translation to clinical practice 2–4 . Moreover, an interest in the large animal model is more closely aligned because of the similarity in size compared to the human spinal cord 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…However, significant anatomical, functional, molecular, and pathological differences between rodent and human spinal cords have also been cited as possible reasons for the lack of translation to clinical practice 2–4 . Moreover, an interest in the large animal model is more closely aligned because of the similarity in size compared to the human spinal cord 4,5 . Advantages of this model include large cord size, cerebrospinal fluid/cord ratios, neuroanatomical similarity to the human spinal cord, and physiological similarities to humans 6–11 .…”

Section: Introductionmentioning

confidence: 99%

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Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury

Ahmed,

Medina‐Aguinaga,

Adams

et al. 2023

Ann Clin Transl Neurol

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ObjectivesTo explore filtered diffusion‐weighted imaging (fDWI), in comparison with conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), as a predictor for long‐term locomotor and urodynamic (UD) outcomes in Yucatan minipig model of spinal cord injury (SCI). Additionally, electrical conductivity of neural tissue using D‐waves above and below the injury was measured to assess correlations between fDWI and D‐waves data.MethodsEleven minipigs with contusion SCI at T8‐T10 level underwent MRI at 3T 4 h. post‐SCI. Parameters extracted from region of interest analysis included Daxial from fDWI at injury site, fractional anisotropy and radial diffusivity from DTI above the injury site along with measures of edema length and cord width at injury site from T2‐weighted images. Locomotor recovery was assessed pre‐ and weekly post‐SCI through porcine thoracic injury behavior scale (PTIBS) and UD were performed pre‐ and at 12 weeks of SCI. D‐waves latency and amplitude differences were recorded before and immediately after SCI.ResultsTwo groups of pigs were found based on the PTIBS at week 12 (p < 0.0001) post‐SCI and were labeled “poor” and “good” recovery. D‐waves amplitude decreased below injury and increased above injury. UD outcomes pre/post SCI changed significantly. Conventional MRI metrics from T2‐weighted images were significantly correlated with diffusion MRI metrics. Daxial at injury epicenter was diminished by over 50% shortly after SCI, and it differentiated between good and poor locomotor recovery and UD outcomes.InterpretationSimilar to small animal studies, fDWI from acute imaging after SCI is a promising predictor for functional outcomes in large animals.

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Porcine spinal cord injury model for translational research across multiple functional systems

Cited by 10 publications

References 108 publications

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model—A Preliminary Study

Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury

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