Skip to main content
SpringerLink
Log in

Rabbit Spinal Cord Ischemia Model for the Development of Neuroprotective Treatments

  • Chapter
  • First Online:
Neuroprotective Therapy for Stroke and Ischemic Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Ischemic spinal cord injury (SCI) is one of the most morbid complications of aortic operations and traumatic injury. Numerous animal models have been created to try to understand the pathogenesis of spinal cord injury and to find treatment options. In this chapter, different animal spinal cord injury models are discussed. An overview of potential spinal cord injury therapeutic agents that are studied in the literature is presented as well. Finally, a new minimally invasive rabbit spinal cord ischemia model that uses a transfemoral intra-aortic balloon occlusion and neuromonitoring with motor-evoked potentials (MEPs) is presented. This rabbit model has the potential to aid in novel therapeutic drug development for early ischemic SCI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Greenberg RK, Lu Q, Roselli EE, Svensson LG, Moon MC, Hernandez AV et al (2008) Contemporary analysis of descending thoracic and thoracoabdominal aneurysm repair: a comparison of endovascular and open techniques. Circulation 118(8):808–817

    Article  PubMed  Google Scholar 

  2. Makaroun MS, Dillavou ED, Kee ST, Sicard G, Chaikof E, Bavaria J et al (2005) Endovascular treatment of thoracic aortic aneurysms: results of the phase II multicenter trial of the GORE TAG thoracic endoprosthesis. J Vasc Surg 41(1):1–9

    Article  PubMed  Google Scholar 

  3. Svensson LG (2005) Paralysis after aortic surgery: in search of lost cord function. Surgeon 3(6):396–405

    Article  CAS  PubMed  Google Scholar 

  4. Dillavou ED, Makaroun MS (2008) Predictors of morbidity and mortality with endovascular and open thoracic aneurysm repair. J Vasc Surg 48(5):1114–1119; discussion 1119–1120

    Article  PubMed  Google Scholar 

  5. Khoynezhad A, Kruse M (2008) Spinal cord injury and stroke following thoracic endovascular aortic repair: a risk analysis and review of the literature. Ital J Vasc Endovasc Surg 14(3):221–229

    Google Scholar 

  6. Ullery BW, Cheung AT, Fairman RM, Jackson BM, Woo EY, Bavaria J et al (2011) Risk factors, outcomes, and clinical manifestations of spinal cord ischemia following thoracic endovascular aortic repair. J Vasc Surg 54(3):677–684

    Article  PubMed  Google Scholar 

  7. Wong DR, Coselli JS, Amerman K, Bozinovski J, Carter SA, Vaughn WK et al (2007) Delayed spinal cord deficits after thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 83(4):1345–1355; discussion 1355

    Article  PubMed  Google Scholar 

  8. Lim PAC, Tow AM (2007) Recovery and regeneration after spinal cord injury: a review and summary of recent literature. Ann Acad Med Singapore 36(1):49–57

    PubMed  Google Scholar 

  9. Aslan A, Cemek M, Eser O, Altunbaş K, Buyukokuroglu ME, Cosar M et al (2009) Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study. Eur Spine J 18(3):336–344

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lima B, Nowicki ER, Blackstone EH, Williams SJ, Roselli EE, Sabik JF et al (2012) Spinal cord protective strategies during descending and thoracoabdominal aortic aneurysm repair in the modern era: the role of intrathecal papaverine. J Thorac Cardiovasc Surg 143(4):945–952.e1

    Article  CAS  PubMed  Google Scholar 

  11. Onose G, Anghelescu A, Muresanu DF, Padure L, Haras MA, Chendreanu CO et al (2009) A review of published reports on neuroprotection in spinal cord injury. Spinal Cord 47(10):716–726

    Article  CAS  PubMed  Google Scholar 

  12. Tran TP, Khoynezhad A (2009) Current management of type B aortic dissection. Vasc Health Risk Manag 5(1):53–63

    PubMed  PubMed Central  Google Scholar 

  13. Safi HJ, Miller CC, Huynh TTT, Estrera AL, Porat EE, Winnerkvist AN et al (2003) Distal aortic perfusion and cerebrospinal fluid drainage for thoracoabdominal and descending thoracic aortic repair: ten years of organ protection. Ann Surg 238(3):372–380; discussion 380–381

    PubMed  PubMed Central  Google Scholar 

  14. Hsu CC-T, Kwan GNC, van Driel ML, Rophael JA (2012) Distal aortic perfusion during thoracoabdominal aneurysm repair for prevention of paraplegia. Cochrane Database Syst Rev 3, CD008197

    Google Scholar 

  15. Khoynezhad A, Donayre CE, Bui H, Kopchok GE, Walot I, White RA (2007) Risk factors of neurologic deficit after thoracic aortic endografting. Ann Thorac Surg 83(2):S882–S889; discussion S890–892

    Article  PubMed  Google Scholar 

  16. Khoynezhad A, Donayre CE, Smith J, Kopchok GE, Walot I, White RA (2008) Risk factors for early and late mortality after thoracic endovascular aortic repair. J Thorac Cardiovasc Surg 135(5):1103–1109, 1109.e1–4

    Article  PubMed  Google Scholar 

  17. Khoynezhad A, Bello R, Smego DR, Nwakanma L, Plestis KA (2005) Improved outcome after repair of descending and thoracoabdominal aortic aneurysms using modern adjuncts. Interact Cardiovasc Thorac Surg 4(6):574–576

    Article  PubMed  Google Scholar 

  18. Yacoub A, Hajec MC, Stanger R, Wan W, Young H, Mathern BE (2014) Neuroprotective effects of perfluorocarbon (oxycyte) after contusive spinal cord injury. J Neurotrauma 31(3):256–267

    Article  PubMed  PubMed Central  Google Scholar 

  19. Schroeder JL, Highsmith JM, Young HF, Mathern BE (2008) Reduction of hypoxia by perfluorocarbon emulsion in a traumatic spinal cord injury model. J Neurosurg Spine 9(2):213–220

    Article  PubMed  Google Scholar 

  20. Mahon RT, Auker CR, Bradley SG, Mendelson A, Hall AA (2013) The emulsified perfluorocarbon oxycyte improves spinal cord injury in a swine model of decompression sickness. Spinal Cord 51(3):188–192

    Article  CAS  PubMed  Google Scholar 

  21. Wu Y, Satkunendrarajah K, Teng Y, Chow DS-L, Buttigieg J, Fehlings MG (2013) Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury. J Neurotrauma 30(6):441–452

    Article  PubMed  PubMed Central  Google Scholar 

  22. Schwartz G, Fehlings MG (2001) Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. J Neurosurg 94(2 Suppl):245–256

    CAS  PubMed  Google Scholar 

  23. Springer JE, Azbill RD, Kennedy SE, George J, Geddes JW (1997) Rapid calpain I activation and cytoskeletal protein degradation following traumatic spinal cord injury: attenuation with riluzole pretreatment. J Neurochem 69(4):1592–1600

    Article  CAS  PubMed  Google Scholar 

  24. Grossman RG, Fehlings MG, Frankowski RF, Burau KD, Chow DSL, Tator C et al (2014) A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma 31(3):239–255

    Article  PubMed  PubMed Central  Google Scholar 

  25. Banik NL, Powers JM, Hogan EL (1980) The effects of spinal cord trauma on myelin. J Neuropathol Exp Neurol 39(3):232–244

    Article  CAS  PubMed  Google Scholar 

  26. Banik NL, Hogan EL, Powers JM, Whetstine LJ (1982) Degradation of cytoskeletal proteins in experimental spinal cord injury. Neurochem Res 7(12):1465–1475

    Article  CAS  PubMed  Google Scholar 

  27. Samantaray S, Sribnick EA, Das A, Knaryan VH, Matzelle DD, Yallapragada AV et al (2008) Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 44(4):348–357

    Article  CAS  PubMed  Google Scholar 

  28. Bracken MB (1992) Pharmacological treatment of acute spinal cord injury: current status and future prospects. Paraplegia 30(2):102–107

    Article  CAS  PubMed  Google Scholar 

  29. Ducker TB, Hamit HF (1969) Experimental treatments of acute spinal cord injury. J Neurosurg 30(6):693–697

    Article  CAS  PubMed  Google Scholar 

  30. Park S-W, Yi J-H, Miranpuri G, Satriotomo I, Bowen K, Resnick DK et al (2006) Thiazolidinedione Class of peroxisome proliferator-activated receptor agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J Pharmacol Exp Ther 320(3):1002–1012

    Article  PubMed  Google Scholar 

  31. Byrnes KR, Stoica BA, Fricke S, Di Giovanni S, Faden AI (2007) Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain 130(11):2977–2992

    Article  PubMed  Google Scholar 

  32. Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John HR (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135(4):1224–1236

    Article  PubMed  Google Scholar 

  33. Siriphorn A, Dunham KA, Chompoopong S, Floyd CL (2012) Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol 520(12):2630–2646

    Article  CAS  PubMed  Google Scholar 

  34. Samantaray S, Smith JA, Das A, Matzelle DD, Varma AK, Ray SK et al (2011) Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochem Res 36(10):1809–1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sribnick EA, Samantaray S, Das A, Smith J, Matzelle DD, Ray SK et al (2010) Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats. J Neurosci Res 88(8):1738–1750

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen S-H, Yeh C-H, Lin MY-S, Kang C-Y, Chu C-C, Chang F-M et al (2010) Premarin improves outcomes of spinal cord injury in male rats through stimulating both angiogenesis and neurogenesis. Crit Care Med 38(10):2043–2051

    Article  PubMed  Google Scholar 

  37. Lee JY, Choi SY, Oh TH, Yune TY (2012) 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. Endocrinology 153(8):3815–3827

    Article  CAS  PubMed  Google Scholar 

  38. Hunt D, Coffin RS, Anderson PN (2002) The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review. J Neurocytol 31(2):93–120

    Article  CAS  PubMed  Google Scholar 

  39. Thomas AJ, Nockels RP, Pan HQ, Shaffrey CI, Chopp M (1999) Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine 24(20):2134–2138

    Article  CAS  PubMed  Google Scholar 

  40. De Nicola AF, Gonzalez SL, Labombarda F, González Deniselle MC, Garay L, Guennoun R et al (2006) Progesterone treatment of spinal cord injury: effects on receptors, neurotrophins, and myelination. J Mol Neurosci MN 28(1):3–15

    Article  PubMed  Google Scholar 

  41. Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324(26):1829–1838

    Article  CAS  PubMed  Google Scholar 

  42. Geisler FH, Coleman WP, Grieco G, Poonian D, Sygen Study Group (2001) The Sygen multicenter acute spinal cord injury study. Spine 26(24 Suppl):S87–S98

    Article  CAS  PubMed  Google Scholar 

  43. Bell MT, Reece TB, Smith PD, Mares J, Weyant MJ, Cleveland JC et al (2014) Reproducable paraplegia by thoracic aortic occlusion in a murine model of spinal cord ischemia-reperfusion. J Vis Exp 85

    Google Scholar 

  44. Awad H, Ankeny DP, Guan Z, Wei P, McTigue DM, Popovich PG (2010) A mouse model of ischemic spinal cord injury with delayed paralysis caused by aortic cross-clamping. Anesthesiology 113(4):880–891

    Article  PubMed  PubMed Central  Google Scholar 

  45. Böckler D, Kotelis D, Kohlhof P, von Tengg-Kobligk H, Mansmann U, Zink W et al (2007) Spinal cord ischemia after endovascular repair of the descending thoracic aorta in a sheep model. Eur J Vasc Endovasc Surg 34(4):461–469

    Article  PubMed  Google Scholar 

  46. Moore WM, Hollier LH (1991) The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. Ann Surg 213(5):427–431; discussion 431–432

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zivin JA, DeGirolami U (1980) Spinal cord infarction: a highly reproducible stroke model. Stroke 11(2):200–202

    Article  CAS  PubMed  Google Scholar 

  48. Cheng MK, Robertson C, Grossman RG, Foltz R, Williams V (1984) Neurological outcome correlated with spinal evoked potentials in a spinal cord ischemia model. J Neurosurg 60(4):786–795

    Article  CAS  PubMed  Google Scholar 

  49. Saba T, Manduz S, Sapmaz I, Tunel A, Aker H, Dogan K (2007) Neuroprotective effects of diltiazem in rabbits with occluded aorta. Rev Bras Cir Cardiovasc 22(4):416–424

    Article  PubMed  Google Scholar 

  50. Waterford SD, Rastegar M, Goodwin E, Lapchak PA, Juan V, Haji F et al (2015) Methodology of motor evoked potentials in a rabbit model. Transl Stroke Res 6(5):399–406

    Article  PubMed  Google Scholar 

  51. Ehrlich M, Knolle E, Ciovica R, Böck P, Turkof E, Grabenwöger M et al (1999) Memantine for prevention of spinal cord injury in a rabbit model. J Thorac Cardiovasc Surg 117(2):285–291

    Article  CAS  PubMed  Google Scholar 

  52. Panthee N, Ono M, Morota T, Tanaka T, Itoda Y, Ikemura M et al (2014) Paraplegia prevention by oral pretreatment with memantine in a rabbit model. J Thorac Cardiovasc Surg 5

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiothoracic Surgery, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Suite A3306, Los Angeles, CA, 90048, USA

    Daisy Chou M.D., Anja Muehle M.D. & Ali Khoynezhad M.D., Ph.D., F.A.C.S.

  2. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Paul A. Lapchak Ph.D., F.A.H.A.

Authors
  1. Daisy Chou M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anja Muehle M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Lapchak Ph.D., F.A.H.A.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali Khoynezhad M.D., Ph.D., F.A.C.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Khoynezhad M.D., Ph.D., F.A.C.S. .

Editor information

Editors and Affiliations

  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Chou, D., Muehle, A., Lapchak, P.A., Khoynezhad, A. (2017). Rabbit Spinal Cord Ischemia Model for the Development of Neuroprotective Treatments. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_29

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-45345-3_29

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45344-6

  • Online ISBN: 978-3-319-45345-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation