ESTABLISHMENT OF A MODEL OF ISCHEMIC INTERVERTEBRAL DISC DEGENERATION IN RHESUS MACAQUES_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WEIFuxin , WANGLe , ZHOUZhiyu , CUIShangbin ,  LIUShaoyu , ZOUXuenong , ZHONGRui , LIANGZijian

Department of Spinal Surgery of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou Guangdong, 510080, P. R. China;

Corresponding author：

LIUShaoyu, Email: gzsyliu@tom.com

Keywords：

Interertebral disk degeneration; T1ρ spin-lock imaging; T2-mapping; Rhesus macaques

DOI：

10.7507/1002-1892.20140109

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Objective To establish the degenerative disc animal model in rhesus macaques and to verify its reliability with T1ρ, spin-lock imaging and T2-mapping MRI and histological observation. Methods Twelve female rhesus macaques (aged 4-6 years, weighing 4.4-6.1 kg) were enrolled in the study. The L_{5, 6} intervertebral disk was used for the experimental group by injecting 1 mL bleomycin A5 (2 mg/mL) to its adjacent endplates to induce degeneration, and the L_4,5 intervertebral disk for the control group by injecting 1 mL normal sodium to its adjacent endplates. T1ρ and T2-mapping relaxation time was examined by using MRI, and the histological observation was performed to evaluate the process of degeneration at 1, 4, and 12 weeks after operation. Results There was no significant change of T1ρ, T2 map relaxation time in the control group at different time points before and after operation (P>0.05). In the experimental group, there was a significant decrease of T1ρ relaxation time from 4 weeks after operation, showing significant difference when compared with the values at pre-operation and 1 week after operation (P<0.05). The T2 map relaxation time decreased significantly at 12 weeks after operation, showing significant difference when compared with the values at the other time points (P<0.05). There was no significant difference between 2 groups at the other time points (P>0.05) except T1ρ relaxation time at 4 and 12 weeks and T2 map relaxation time at 12 weeks (P<0.05). No significant change of the percentage of the high intensity area of the operated discs was observed on T2WI of MRI after operation in 2 groups (P>0.05). The histological results showed that the number of nucleus pulposus decreased and arranged irregularly at 4 weeks, and there were fibrosis changes of nucleus pulposus and cleft of the inner annulus fibrosus at 12 weeks after operation in the experimental group. Conclusion Degeneration of lumbar intervertebral disc in rhesus macaques can be induced by injecting bleomycin A5. T1ρ-MRI may be an effective method to evaluate early degeneration of intervertebral disc.

Citation： WEIFuxin, WANGLe, ZHOUZhiyu, CUIShangbin, LIUShaoyu, ZOUXuenong, ZHONGRui, LIANGZijian. ESTABLISHMENT OF A MODEL OF ISCHEMIC INTERVERTEBRAL DISC DEGENERATION IN RHESUS MACAQUES. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(4): 485-490. doi: 10.7507/1002-1892.20140109 Copy

1.	Cinotti G, Della Rocca C, Romeo S, et al. Degenerative changes of porcine intervertebral disc induced by vertebral endplate injuries. Spine (Phila Pa 1976), 2005, 30(2):174-180.
2.	张闻力, 李涛, 龚全, 等. 三种方法建立兔椎间盘退变模型的比较研究. 中国修复重建外科杂志, 2010, 24(1):41-45.
3.	Maclean JJ, Lee CR, Grad S, et al. Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. Spine (Phila Pa 1976), 2003, 28(10):973-981.
4.	Li B, Zheng XF, Ni BB, et al. Reduced expression of insulin-like growth factor 1 receptor leads to accelerated intervertebral disc degeneration in mice. Int J Immunopathol Pharmacol, 2013, 26(2):337-347.
5.	Lotz JC. Animal models of intervertebral disc degeneration:lessons learned. Spine (Phila Pa 1976), 2004, 29(23):2742-2750.
6.	Martin JT, Gorth DJ, Beattie EE, et al. Needle puncture injury causes acute and long-term mechanical deficiency in a mouse model of intervertebral disc degeneration. J Orthop Res, 2013, 31(8):1276-1282.
7.	Xia M, Zhu Y. Fibronectin fragment activation of ERK increasing integrin α₅ and β₁ subunit expression to degenerate nucleus pulposus cells. J OrthoP Res, 2011, 29(4):556-561.
8.	Hamrick MW, Pennington C, Byron CD. Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin). J Orthop Res, 2003, 21(6):1025-1032.
9.	侯昌龙, 杨建勇, 庄文权, 等. 制作兔腰椎终板下缺血模型 MRI与病理学变化验证的可行性. 中国组织工程研究与临床康复, 2010, 14(2):280-284.
10.	Johannessen W, Auerbach JD, Wheaton AJ, et al. Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging. Spine (Phila Pa 1976), 2006, 31(11):1253-1257.
11.	Zuo J, Saadat E, Romero A, et al. Assessment of intervertebral disc degeneration with magnetic resonance single-voxel spectroscopy. Magn Reson Med, 2009, 62(5):1140-1146.
12.	Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976), 2001, 26(17):1873-1878.
13.	Benneker LM, Heini PF, Alini M, et al. 2004 Young Investigator Award Winner:Vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration. Spine (Phila Pa 1976), 2005, 30(2):167-173.
14.	Hadjipavlou AG, Tzermiadianos MN, Bogduk N, et al. The pathophysiology of disc degeneration:a critical review. J Bone Joint Surg (Br), 2008, 90(10):1261-1270.
15.	Accadbled F, Laffosse JM, Ambard D, et al. Influence of location, fluid flow direction and tissue maturity on the macroscopic permeability of vertebral end plates. Spine (Phila Pa 1976), 2008, 33(6):612-619.
16.	Blumenkrantz G, Zuo J, Li X, et al. In vivo 3.0-tesla magnetic resonance T1rho and T2 relaxation mapping in subjects with intervertebral disc degeneration and clinical symptoms. Magn Reson Med, 2010, 63(5):1193-1200.
17.	Takashima H, Takebayashi T, Yoshimoto M, et al. Correlation between T2 relaxation time and intervertebral disk degeneration. Skeletal Radiol, 2012, 41(2):163-167.
18.	Borthakur A, Maurer PM, Fenty M, et al. T1ρ magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain. Spine (Phila Pa 1976), 2011, 36(25):2190-2196.
19.	Zobel BB, Vadalà G, Del Vescovo R, et al. T1ρ magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults. Spine (Phila Pa 1976), 2012, 37(14):1224-1230.
20.	Wang YX, Zhao F, Griffith JF, et al. T1rho and T2 relaxation times for lumbar disc degeneration:an in vivo comparative study at 3.0-Tesla MRI. Eur Radiol, 2013, 23(1):228-234.

1. Cinotti G, Della Rocca C, Romeo S, et al. Degenerative changes of porcine intervertebral disc induced by vertebral endplate injuries. Spine (Phila Pa 1976), 2005, 30(2):174-180.
2. 张闻力, 李涛, 龚全, 等. 三种方法建立兔椎间盘退变模型的比较研究. 中国修复重建外科杂志, 2010, 24(1):41-45.
3. Maclean JJ, Lee CR, Grad S, et al. Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. Spine (Phila Pa 1976), 2003, 28(10):973-981.
4. Li B, Zheng XF, Ni BB, et al. Reduced expression of insulin-like growth factor 1 receptor leads to accelerated intervertebral disc degeneration in mice. Int J Immunopathol Pharmacol, 2013, 26(2):337-347.
5. Lotz JC. Animal models of intervertebral disc degeneration:lessons learned. Spine (Phila Pa 1976), 2004, 29(23):2742-2750.
6. Martin JT, Gorth DJ, Beattie EE, et al. Needle puncture injury causes acute and long-term mechanical deficiency in a mouse model of intervertebral disc degeneration. J Orthop Res, 2013, 31(8):1276-1282.
7. Xia M, Zhu Y. Fibronectin fragment activation of ERK increasing integrin α₅ and β₁ subunit expression to degenerate nucleus pulposus cells. J OrthoP Res, 2011, 29(4):556-561.
8. Hamrick MW, Pennington C, Byron CD. Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin). J Orthop Res, 2003, 21(6):1025-1032.
9. 侯昌龙, 杨建勇, 庄文权, 等. 制作兔腰椎终板下缺血模型 MRI与病理学变化验证的可行性. 中国组织工程研究与临床康复, 2010, 14(2):280-284.
10. Johannessen W, Auerbach JD, Wheaton AJ, et al. Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging. Spine (Phila Pa 1976), 2006, 31(11):1253-1257.
11. Zuo J, Saadat E, Romero A, et al. Assessment of intervertebral disc degeneration with magnetic resonance single-voxel spectroscopy. Magn Reson Med, 2009, 62(5):1140-1146.
12. Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976), 2001, 26(17):1873-1878.
13. Benneker LM, Heini PF, Alini M, et al. 2004 Young Investigator Award Winner:Vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration. Spine (Phila Pa 1976), 2005, 30(2):167-173.
14. Hadjipavlou AG, Tzermiadianos MN, Bogduk N, et al. The pathophysiology of disc degeneration:a critical review. J Bone Joint Surg (Br), 2008, 90(10):1261-1270.
15. Accadbled F, Laffosse JM, Ambard D, et al. Influence of location, fluid flow direction and tissue maturity on the macroscopic permeability of vertebral end plates. Spine (Phila Pa 1976), 2008, 33(6):612-619.
16. Blumenkrantz G, Zuo J, Li X, et al. In vivo 3.0-tesla magnetic resonance T1rho and T2 relaxation mapping in subjects with intervertebral disc degeneration and clinical symptoms. Magn Reson Med, 2010, 63(5):1193-1200.
17. Takashima H, Takebayashi T, Yoshimoto M, et al. Correlation between T2 relaxation time and intervertebral disk degeneration. Skeletal Radiol, 2012, 41(2):163-167.
18. Borthakur A, Maurer PM, Fenty M, et al. T1ρ magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain. Spine (Phila Pa 1976), 2011, 36(25):2190-2196.
19. Zobel BB, Vadalà G, Del Vescovo R, et al. T1ρ magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults. Spine (Phila Pa 1976), 2012, 37(14):1224-1230.
20. Wang YX, Zhao F, Griffith JF, et al. T1rho and T2 relaxation times for lumbar disc degeneration:an in vivo comparative study at 3.0-Tesla MRI. Eur Radiol, 2013, 23(1):228-234.

Chinese Journal of Reparative and Reconstructive Surgery

ESTABLISHMENT OF A MODEL OF ISCHEMIC INTERVERTEBRAL DISC DEGENERATION IN RHESUS MACAQUES

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