J Korean Neurosurg Soc.  2018 Sep;61(5):539-547. 10.3340/jkns.2017.0276.

Review of the UBC Porcine Model of Traumatic Spinal Cord Injury

Affiliations
  • 1Department of Neurosurgery, Kyungpook National University Hospital, Daegu, Korea.
  • 2Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea.
  • 3International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada. brian.kwon@ubc.ca
  • 4Vancouver Spine Surgery Institute, Department of Orthopaedics, University of British Columbia, Vancouver, Canada.

Abstract

Traumatic spinal cord injury (SCI) research has recently focused on the use of rat and mouse models for in vivo SCI experiments. Such small rodent SCI models are invaluable for the field, and much has been discovered about the biologic and physiologic aspects of SCI from these models. It has been difficult, however, to reproduce the efficacy of treatments found to produce neurologic benefits in rodent SCI models when these treatments are tested in human clinical trials. A large animal model may have advantages for translational research where anatomical, physiological, or genetic similarities to humans may be more relevant for pre-clinically evaluating novel therapies. Here, we review the work carried out at the University of British Columbia (UBC) on a large animal model of SCI that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a useful intermediary in the pre-clinical testing of novel pharmacological treatments, cell-based therapies, and the "bedside back to bench" translation of human clinical observations, which require preclinical testing in an applicable animal model.

Keyword

Spinal cord injuries; Porcine model; Translational medical research; Preclinical testing

MeSH Terms

Animals
British Columbia
Humans
Mice
Models, Animal
Rats
Rodentia
Spinal Cord Injuries*
Spinal Cord*
Swine
Translational Medical Research

Figure

  • Fig. 1. Axial image from magnetic resonance imaging. Left to right, Sprague-Dawley rat, Yucatan miniature pig, and human at T10. The width of the porcine spinal cord is close to a human spinal cord and a prominent layer of cerebrospinal fluid (CSF) surrounds the porcine and human spinal cord. The transverse diameter of the rat, pig, and human spinal cord on these sections are 3.2, 7.0, and 8.3 mm, respectively. Scale bar=10 mm.

  • Fig. 2. The pig in prone position on the surgical table. Standard monitoring is performed for heart rate, respiratory rate, blood pressure, end tidal carbon dioxide, inspired and expired isoflurane levels, and oxygen saturation.

  • Fig. 3. Weight drop impactor devices. This system provides a mechanism to induce a contusion with compression injury, the most commonly observed type of injury in human SCI patients. A and B : The individual components of the injury device: guide rail, position sensor, trigger system, weight drop with force sensing cylindrical tip, static weight and an articulating fixation arm. C : Impactor mounted on the animals after weight drop injury. After the 50 g weight drop an additional 100 g static weight is applied for the determined period of time.

  • Fig. 4. For the measurement of the white and gray matter preserved areas, a series of cross-sections were stained with Eriochrome cyanide. The spared white matter was defined as a region showing dense blue staining. The preserved gray matter is defined by the color of the stain (×20) and the shape. We defined uninjured gray matter as tissue containing normal gray matter cytoarchitecture with visible neutral red staining speck.

  • Fig. 5. Microdialysis can be used for evaluating the metabolic changes after spinal cord injury. After laminectomy, probes are inserted into the spinal cord through the dura using customized guide cannulae (A). The microdialysis probe is placed at the center, with the oxygenation and blood flow sensor to the right and the pressure sensor to the left. Probes are inserted into the spinal cord at a 45-degree angle (B) and the probe tips end 0.17 and 2.17 cm from the injury epicenter.


Reference

References

1. Bang WS, Kim KT, Cho DC, Kim HJ, Sung JK. Valproic Acid increases expression of neuronal stem/progenitor cell in spinal cord injury. J Korean Neurosurg Soc. 54:8–13. 2013.
Article
2. Browne KD, Chen XH, Meaney DF, Smith DH. Mild traumatic brain injury and diffuse axonal injury in swine. J Neurotrauma. 28:1747–1755. 2011.
Article
3. Donati G, Kapetanios A, Dubois-Dauphin M, Pournaras CJ. Caspaserelated apoptosis in chronic ischaemic microangiopathy following experimental vein occlusion in mini-pigs. Acta Ophthalmol. 86:302–306. 2008.
Article
4. Jones CF, Lee JH, Burstyn U, Okon EB, Kwon BK, Cripton PA. Cerebrospinal fluid pressures resulting from experimental traumatic spinal cord injuries in a pig model. J Biomech Eng. 135:101005. 2013.
Article
5. Jones CF, Lee JH, Kwon BK, Cripton PA. Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury: laboratory investigation. J Neurosurg Spine. 16:624–635. 2012.
Article
6. Kim KT, Kim HJ, Cho DC, Bae JS, Park SW. Substance P stimulates proliferation of spinal neural stem cells in spinal cord injury via the mitogenactivated protein kinase signaling pathway. Spine J. 15:2055–2065. 2015.
Article
7. Kim KT, Kim MJ, Cho DC, Park SH, Hwang JH, Sung JK, et al. The neuroprotective effect of treatment with curcumin in acute spinal cord injury: laboratory investigation. Neurol Med Chir (Tokyo). 54:387–394. 2014.
Article
8. Kim KT, Nam TK, Park YS, Kim YB, Park SW. Neuroprotective effect of anthocyanin on experimental traumatic spinal cord injury. J Korean Neurosurg Soc. 49:205–211. 2011.
Article
9. Kuluz JW, Prado R, He D, Zhao W, Dietrich WD, Watson B. New pediatric model of ischemic stroke in infant piglets by photothrombosis: acute changes in cerebral blood flow, microvasculature, and early histopathology. Stroke. 38:1932–1937. 2007.
Article
10. Kwon BK, Borisoff JF, Tetzlaff W. Molecular targets for therapeutic intervention after spinal cord injury. Mol Interv. 2:244–258. 2002.
Article
11. Kwon BK, Hillyer J, Tetzlaff W. Translational research in spinal cord injury: a survey of opinion from the SCI community. J Neurotrauma. 27:21–33. 2010.
Article
12. Kwon BK, Roy J, Lee JH, Okon E, Zhang H, Marx JC, et al. Magnesium chloride in a polyethylene glycol formulation as a neuroprotective therapy for acute spinal cord injury: preclinical refinement and optimization. J Neurotrauma. 26:1379–1393. 2009.
Article
13. Kwon BK, Streijger F, Fallah N, Noonan VK, Bélanger LM, Ritchie L, et al. Cerebrospinal fluid biomarkers to stratify injury severity and predict outcome in human traumatic spinal cord injury. J Neurotrauma. 34:567–580. 2017.
Article
14. Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J. 4:451–464. 2004.
Article
15. Lee JH, Jones CF, Okon EB, Anderson L, Tigchelaar S, Kooner P, et al. A novel porcine model of traumatic thoracic spinal cord injury. J Neurotrauma. 30:142–159. 2013.
Article
16. Lee JH, Roy J, Sohn HM, Cheong M, Liu J, Stammers AT, et al. Magnesium in a polyethylene glycol formulation provides neuroprotection after unilateral cervical spinal cord injury. Spine (Phila Pa 1976). 35:2041–2048. 2010.
Article
17. Mordasini P, Frabetti N, Gralla J, Schroth G, Fischer U, Arnold M, et al. In vivo evaluation of the first dedicated combined flow-restoration and mechanical thrombectomy device in a swine model of acute vessel occlusion. AJNR Am J Neuroradiol. 32:294–300. 2011.
Article
18. Okon EB, Streijger F, Lee JH, Anderson LM, Russell AK, Kwon BK. Intraparenchymal microdialysis after acute spinal cord injury reveals differential metabolic responses to contusive versus compressive mechanisms of injury. J Neurotrauma. 30:1564–1576. 2013.
Article
19. Rabchevsky AG, Fugaccia I, Sullivan PG, Scheff SW. Cyclosporin A treatment following spinal cord injury to the rat: behavioral effects and stereological assessment of tissue sparing. J Neurotrauma. 18:513–522. 2001.
Article
20. Streijger F, Lee JH, Chak J, Dressler D, Manouchehri N, Okon EB, et al. The effect of whole-body resonance vibration in a porcine model of spinal cord injury. J Neurotrauma. 32:908–921. 2015.
Article
21. Streijger F, Lee JH, Manouchehri N, Melnyk AD, Chak J, Tigchelaar S, et al. Responses of the acutely injured spinal cord to vibration that simulates transport in helicopters or mine-resistant ambush-protected vehicles. J Neurotrauma. 33:2217–2226. 2016.
Article
22. Streijger F, Lee JH, Manouchehri N, Okon EB, Tigchelaar S, Anderson LM, et al. The evaluation of magnesium chloride within a polyethylene glycol formulation in a porcine model of acute spinal cord injury. J Neurotrauma. 33:2202–2216. 2016.
Article
23. Streijger F, So K, Manouchehri N, Lee JHT, Okon EB, Shortt K, et al. Changes in pressure, hemodynamics and metabolism within the spinal cord during the first 7-days after injury using a porcine model. J Neurotrauma. 34:3336–3350. 2017.
Article
24. Tator CH. Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery. 59:957–982. discussion 982-987. 2006.
25. Teranishi K, Scultetus A, Haque A, Stern S, Philbin N, Rice J, et al. Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre-hospital resuscitation in a swine model. Injury. 43:585–593. 2012.
Article
26. Tigchelaar S, Streijger F, Sinha S, Flibotte S, Manouchehri N, So K, et al. Serum MicroRNAs reflect injury severity in a large animal model of thoracic spinal cord injury. Sci Rep. 7:1376. 2017.
Article
27. Wernersson R, Schierup MH, Jørgensen FG, Gorodkin J, Panitz F, Staerfeldt HH, et al. Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing. BMC Genomics. 6:70. 2005.
Article
28. Wofford KL, Harris JP, Browne KD, Brown DP, Grovola MR, Mietus CJ, et al. Rapid neuroinflammatory response localized to injured neurons after diffuse traumatic brain injury in swine. Exp Neurol. 290:85–94. 2017.
Article
29. Zurita M, Aguayo C, Bonilla C, Otero L, Rico M, Rodríguez A, et al. The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury. Prog Neurobiol. 97:288–303. 2012.
Article
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