Comparison of the spine structure of animal models of brucellosis.
Abstract
Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. Relevant aspects of Brucella pathogenesis have been intensively investigated in preclinical models. Mice, rats, rabbits, and sheep are representing available models to induce Brucellosis. Evaluation of Brucellar spondylodiscitis may be performed using a large variety of methods, including plain radiography, computed tomography, magnetic resonance imaging, histological analysis, blood test, and bacteria culture. This chapter focuses on these preclinical models of Brucellar spondylodiscitis. The requirements for preclinical models of Brucellar spondylodiscitis, pearls and pitfalls of the preclinical model establishment, and comprehensive analyses of Brucellar spondylodiscitis in animals are also depicted.
Keywords
- Animal models
- Preclinical models
- Brucellar spondylodiscitis
- Brucellosis
1. Introduction
Brucellosis, an infectious disease caused by the
Preclinical models exhibiting symptoms comparable to those in humans are essential for the translation of preclinical findings into clinical practice [10, 11, 12, 13]. Relevant aspects of the Brucella pathogenesis have been intensively investigated in both
This chapter focuses on these preclinical models of Brucellar spondylodiscitis. The requirements for preclinical models of Brucellar spondylodiscitis, pearls and pitfalls of the preclinical model establishment, and comprehensive analyses of Brucellar spondylodiscitis in animal models are also deliberated.
2. Requirements for preclinical models of Brucellar spondylodiscitis
Investigators have previously established Brucellosis models in many diverse animals [15], however the animal candidates for stimulating
The geometrical size and anatomical structure of the animal spine should be comparable to the human spine.
The biomechanical properties of the animal spine should be close to the human spine.
The model needs reflect the clinical nature of the Brucellar spondylodiscitis.
The radiographic characteristics of Brucellar spondylodiscitis in specific animals should be analogous to the human setting.
The generated preclinical data can be translated into the clinical situation and further benefit the clinical treatments.
Species | Characteristics of spine | References |
---|---|---|
Mouse | Significantly smaller size than the human spine Different mechanical loading from the human spine Advantages of easy surgical manipulations | [17, 18] |
Rat | Normalized disc height in rats higher than that in humans Vertebral dimensions varying more in rats than in humans Vertebrae slenderer in rats than in humans | [18, 19] |
Rabbit | Seven lumbar vertebral segments in rabbit and the lowest segment connected to the sacrum (similar to humans) Biomechanical behavior of the lumbar spine comparable with the human lumbar spine | [18, 20, 21] |
Sheep | Spine size larger than humans (particularly in vertebral body height and pedicle height) Similar increasing trend of spinal canal width and depth to humans | [22] |
3. Preclinical models of Brucellar spondylodiscitis
Mice, rats, rabbits, and sheep represent the available candidates to induce Brucellosis [23, 24, 25, 26]. However, the preclinical model of Brucellar spondylodiscitis with a possible high translational efficiency has only been established in rabbits so far [14].
3.1 Mice
Mice are the most extensively used to investigate chronic infections of
The mouse model has been utilized for the evaluation of the efficiency of different pharmacotherapies for human Brucellosis [37, 38, 39]. Several lines of evidence suggest that mice treated with ciprofloxacin, by subcutaneous (40 mg/kg), digestive (200 mg/kg), or intraperitoneal (20 mg/kg) route, are not able to control the infection of
3.2 Rats
The rats, more resistant to
The usefulness of pharmacotherapy has been investigated in the treatment for Brucellosis in the rat model. Geyik
3.3 Rabbits
Compared with other animals, rabbits are medium-sized animals which frequently used in spine research with various advantages [45]. The rabbit spine maintains considerable morphological and structural similarities to the human spine, and its body size allows for an adequate exposure during the surgical interventions [46, 47]. Furthermore, rabbits yield higher possibilities than rodents to successfully translate preclinical discoveries into humans [48, 49]. Similarly, compared with larger animals, radiographic analyses are largely convenient in rabbits particularly for
Age is a critical issue to be considered when establishing a rabbit model of local restricted Brucellar spondylodiscitis. The significant variance of the innate immune response between young and adult rabbits against infections of foreign microbes should be recognized [14]. Virus related studies highlighted the significantly superior innate immune system in young rabbits (<4 weeks) over adult rabbits, which contributed to their distinct susceptibility to virus infections [51, 52, 53]. These data may partially explain the fact that adult rabbits are only partially susceptible to
Of note, despite the animal model for Brucellar spondylodiscitis has been established in rabbits, no studies about its treatments are available for the rabbit Brucellosis.
3.4 Sheep
Although
Oxytetracycline combined with streptomycin were evaluated for eliminating
4. Pearls and pitfalls of the preclinical model establishment
The key to establish the preclinical model is to implant the
5. Comprehensive analyses of Brucellar spondylodiscitis in preclinical models
Several techniques can be applied for the evaluation of Brucellar spondylodiscitis in animals. To observe the targeted vertebral body and intervertebral disc postoperatively,
Classification | MRI characteristics |
---|---|
Discitis | Regional inflammation involving intervertebral disc Disc space narrowing Low signal on T1-weighted image mixing high signal on T2-weighted image |
Spondylitis | Regional inflammation involving adjacent vertebrae Vertebrae diffuse marrow edema Homogeneous or uneven low signal on T1-weighted image of vertebrae |
Paraspinal/ psoas abscess | Regional inflammation involving paraspinal or psoas Paravertebral abscess Psoas abscess |
Appendicitis | Regional inflammation involving appendicitis Low signal on T1-weighted image High signal on T2-weighted image |
Compound | Endemic inflammation involving two or more parts of vertebral and paravertebral structures T1-weighted image reveals incomplete heterogeneous hypointensity T2-weighted image reveals hyperintensity |
6. Preclinical evaluation of therapeutic interventions and vaccines
Pharmacotherapy is the main therapeutic intervention for the treatment of human Brucellosis, including Brucellar spondylodiscitis. Ciprofloxacin, doxycycline, rifampin has been utilized for the evaluation of the efficiency of different pharmacotherapies for human Brucellosis [37, 38, 39]. Different combination of rifampicin, doxycycline, and spiramycin or moxifloxacin were analyzed in rat Brucellosis model for the potential therapeutic options [40, 42]. Oxytetracycline combined with streptomycin were evaluated in the sheep for the test of practical and cost-effective treatment regimen for Brucellosis [59]. Additionally, as a new antibiotic carrier, the microspheres have been used to test for a treatment effect of
Surgery should be performed to treat Brucellar spondylodiscitis if the pharmacotherapy is poorly done. The indications for surgery included the following: persistent pain due to spinal instability, severe or progressive neurologic dysfunction due to nerve root compression by inflammatory granuloma or epidural abscesses, and no response to antibiotic therapy [9, 64]. The preclinical model is critical for the research of the improvement of surgery protocols. However, the rabbit model was originally developed for the study of Brucellar spondylodiscitis. Future studies are needed to further refine the surgical procedures.
By far, the quality of live vaccines that are commercially used for preventing animal Brucellosis is evaluated in mouse models. Live
7. Challenges and outlooks
During the past decades, significant progresses to diagnose and treat the Brucellar spondylodiscitis have been achieved [66, 67, 68, 69]. However, many obstacles still exist to be overcome in order to employ and utilize new strategies to refine early detection, diagnosis, therapy [70, 71]. Regarding the basic research, no appropriate vaccines exist due to an incomplete understanding of the mechanisms of human Brucellosis, including Brucellar spondylodiscitis. Clinically, the early and differential diagnosis of the Brucellar spondylodiscitis is challenging, especially in the early phases of the disease. Also, pharmacotherapy is the main clinical therapeutic modality for Brucellar spondylodiscitis and should be individually tailored; however, medication selection, administration, dosage, and duration are still largely debatable.
The ideal preclinical models should reflect the precise clinical characteristics of the human Brucellar spondylodiscitis and serve as a platform to explore the potential vaccines, examine novel diagnostic methods, and preselect innovative therapeutics [72, 73, 74]. More investigations in the future are still required to determine the optimal clinically relevant large preclinical model, to identify the efficacy-associated factors (e.g. age, joint size, gender, and dosage), to compare possible dissimilarities between models with local contained lesions or systematic spreading.
8. Conclusions
The pathogenesis, diagnosis, and treatment approach of Brucellar spondylodiscitis has recently become a clinical and research focus. Brucellar spondylodiscitis with highly variable clinical manifestations are practically challenging to be mimicked with laboratory preclinical models. More human-relevant preclinical models should be established to provide better insights into the sophisticated mechanism of human Brucellosis and early interventions of Brucellar spondylodiscitis.
References
- 1.
Nicoletti P. Brucellosis: past, present and future. Prilozi. 2010;31(1):21-32 - 2.
Yang H, Zhang S, Wang T, Zhao C, Zhang X, Hu J, et al. Epidemiological Characteristics and Spatiotemporal Trend Analysis of Human Brucellosis in China, 1950-2018. Int J Environ Res Public Health. 2020;17(7) - 3.
Tekin R, Cevik R, Nas K. Noncontiguous multiple-level brucellar spondylodiscitis with an epidural abscess. Rev Soc Bras Med Trop. 2015;48(5):638 - 4.
Turgut M, Turgut AT, Koşar U. Spinal brucellosis: Turkish experience based on 452 cases published during the last century. Acta Neurochir (Wien). 2006;148(10):1033-1044; discussion 44 - 5.
Bozgeyik Z, Ozdemir H, Demirdag K, Ozden M, Sonmezgoz F, Ozgocmen S. Clinical and MRI findings of brucellar spondylodiscitis. Eur J Radiol. 2008;67(1):153-158 - 6.
Zileli M, Ebeoglu A. Brucellar spondylodiscitis. ArgoSpine News & Journal. 2011;23(3):99-104 - 7.
Kutlu M, Ergonul O, Sayın Kutlu S, Guven T, Ustun C, Alp S, et al. Risk factors for occupational brucellosis among veterinary personnel in Turkey. Preventive veterinary medicine. 2014;117 - 8.
Araj GF. Update on laboratory diagnosis of human brucellosis. Int J Antimicrob Agents. 2010;36 Suppl 1:S12-S17 - 9.
Abulizi Y, Cai X, Xu T, Xun C, Sheng W, Gao L, Maimaiti M. Diagnosis and Surgical Treatment of Human Brucellar Spondylodiscitis. J Vis Exp. 2021:e61840 - 10.
Gao L, Guo R, Han Z, Liu J, Chen X. Clinical trial reporting. Lancet. 2020;396(10261):1488-1489 - 11.
Guo R, Gao L, Xu B. Current Evidence of Adult Stem Cells to Enhance Anterior Cruciate Ligament Treatment: A Systematic Review of Animal Trials. Arthroscopy. 2018;34(1):331-40.e2 - 12.
Cai X, Gao L, Cucchiarini M, Madry H. Association of Nicotine with Osteochondrogenesis and Osteoarthritis Development: The State of the Art of Preclinical Research. J Clin Med. 2019;8(10) - 13.
Gao L, Goebel LKH, Orth P, Cucchiarini M, Madry H. Subchondral drilling for articular cartilage repair: a systematic review of translational research. Dis Model Mech. 2018;11(6) - 14.
Cai X, Xu T, Xun C, Abulizi Y, Liu Q, Sheng W, et al. Establishment and Initial Testing of a Medium-Sized, Surgically Feasible Animal Model for Brucellar Spondylodiscitis: A Preliminary Study. Biomed Res Int. 2019;2019:7368627 - 15.
Silva TMA, Costa EA, Paixão TA, Tsolis RM, Santos RL. Laboratory Animal Models for Brucellosis Research. Journal of Biomedicine and Biotechnology. 2011;2011:518323 - 16.
Rajashekara G, Glover DA, Banai M, O'Callaghan D, Splitter GA. Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice. Infect Immun. 2006;74(5):2925-2936 - 17.
Daly C, Ghosh P, Jenkin G, Oehme D, Goldschlager T. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic. BioMed Research International. 2016;2016:5952165 - 18.
O'Connell GD, Vresilovic Ej Fau - Elliott DM, Elliott DM. Comparison of animals used in disc research to human lumbar disc geometry. (1528-1159 (Electronic)) - 19.
Jaumard NV, Leung J Fau - Gokhale AJ, Gokhale Aj Fau - Guarino BB, Guarino Bb Fau - Welch WC, Welch Wc Fau - Winkelstein BA, Winkelstein BA. Relevant Anatomic and Morphological Measurements of the Rat Spine: Considerations for Rodent Models of Human Spine Trauma. (1528-1159 (Electronic)) - 20.
Wu J, Xue J, Huang R, Zheng C, Cui Y, Rao S. A rabbit model of lumbar distraction spinal cord injury. (1878-1632 (Electronic)) - 21.
Kroeber MW, Unglaub F Fau - Wang H, Wang H Fau - Schmid C, Schmid C Fau - Thomsen M, Thomsen M Fau - Nerlich A, Nerlich A Fau - Richter W, et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. (1528-1159 (Electronic)) - 22.
Wilke HJ, Kettler A Fau - Wenger KH, Wenger Kh Fau - Claes LE, Claes LE. Anatomy of the sheep spine and its comparison to the human spine. (0003-276X (Print)) - 23.
Yumuk Z, Küçükbasmaci Ö, Büyükbaba Boral Ö, Küçüker Anğ M, Dundar V. The effects of streptozotocin-induced diabetes on brucellosis of rats. FEMS Immunology & Medical Microbiology. 2003;39(3):275-278 - 24.
If T, Na R. Comparative study of the susceptibility and infectious sensitivity of laboratory animals and sheep to different species of the causative agent of brucellosis. Zhurnal mikrobiologii epidemiologii i immunobiologii. 1971;48:97-101 - 25.
Thorpe BD, Sidwell RW, Lundgren DL. Experimental studies with four species of Brucella in selected wildlife, laboratory, and domestic animals. Am J Trop Med Hyg. 1967;16(5):665-674 - 26.
Huddleson IF, Hallman ET. The Pathogenicity of the Species of the Genus Brucella for Monkeys. The Journal of Infectious Diseases. 1929;45(4):293-303 - 27.
Enright FM, Araya Ln Fau - Elzer PH, Elzer Ph Fau - Rowe GE, Rowe Ge Fau - Winter AJ, Winter AJ. Comparative histopathology in BALB/c mice infected with virulent and attenuated strains of Brucella abortus . (0165-2427 (Print)) - 28.
Stevens MG, Olsen SC, Pugh GW, Jr., Palmer MV. Immune and pathologic responses in mice infected with Brucella abortus 19, RB51, or 2308. Infection and immunity. 1994;62(8):3206-3212 - 29.
Tobias L, Cordes Do Fau - Schurig GG, Schurig GG. Placental pathology of the pregnant mouse inoculated with Brucella abortus strain 2308. (0300-9858 (Print)) - 30.
Izadjoo MJ, Mense Mg Fau - Bhattacharjee AK, Bhattacharjee Ak Fau - Hadfield TL, Hadfield Tl Fau - Crawford RM, Crawford Rm Fau - Hoover DL, Hoover DL. A study on the use of male animal models for developing a live vaccine for brucellosis. (1865-1674 (Print)) - 31.
Kahl-McDonagh MM, Arenas-Gamboa Am Fau - Ficht TA, Ficht TA. Aerosol infection of BALB/c mice with Brucella melitensis and Brucella abortus and protective efficacy against aerosol challenge. (0019-9567 (Print)) - 32.
Young JD. Brucellosis with hepatomegaly and splenomegaly - 33.
Colmenero Jde D, Queipo-Ortuño Mi Fau - Maria Reguera J, Maria Reguera J Fau - Angel Suarez-Muñoz M, Angel Suarez-Muñoz M Fau - Martín-Carballino S, Martín-Carballino S Fau - Morata P, Morata P. Chronic hepatosplenic abscesses in Brucellosis. Clinico-therapeutic features and molecular diagnostic approach. (0732-8893 (Print)) - 34.
Akritidis N, Tzivras M, Delladetsima I, Stefanaki S, Moutsopoulos HM, Pappas G. The Liver in Brucellosis. Clinical Gastroenterology and Hepatology. 2007;5(9):1109-1112 - 35.
Franco MP, Mulder M Fau - Gilman RH, Gilman Rh Fau - Smits HL, Smits HL. Human brucellosis. (1473-3099 (Print)) - 36.
Rajashekara G, Glover Da Fau - Krepps M, Krepps M Fau - Splitter GA, Splitter GA. Temporal analysis of pathogenic events in virulent and avirulent Brucella melitensis infections. (1462-5814 (Print)) - 37.
Prior S, Gander B, Irache JM, Gamazo C. Gentamicin-loaded microspheres for treatment of experimental Brucella abortus infection in mice. J Antimicrob Chemother. 2005;55(6):1032-1036 - 38.
Shasha B, Lang R, Rubinstein E. Therapy of experimental murine brucellosis with streptomycin, co-trimoxazole, ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin. Antimicrob Agents Chemother. 1992;36(5):973-976 - 39.
Arda B, Tunçel M, Yaimazhan T, Gökengin D, Gürel O. Efficacy of oral levofloxacin and dirithromycin alone and in combination with rifampicin in the treatment of experimental murine Brucella abortus infection. Int J Antimicrob Agents. 2004;23(2):204-207 - 40.
Geyik MF, Dikici B Fau - Kokoglu OF, Kokoglu Of Fau - Bosnak M, Bosnak M Fau - Celen MK, Celen Mk Fau - Hosoglu S, Hosoglu S Fau - Ayaz C, et al. Therapeutic effect of spiramycin in brucellosis. (1328-8067 (Print)) - 41.
Yumuk Z, Dundar V. The effect of long-term ethanol feeding on efficacy of doxycycline plus rifampicin in the treatment of experimental brucellosis caused by Brucella melitensis in rats. (1120-009X (Print)) - 42.
Sezak N, Kuruuzum Z Fau - Cakir N, Cakir N Fau - Yuce A, Yuce A. Comparison of rifampicin and moxifloxacin efficacy in an experimental model of animal brucellosis. (1973-9478 (Electronic)) - 43.
Siddiqur RM, Kirl BB. Clinical and pathological findings in experimental brucellosis in pregnant rats. (1972-2680 (Electronic)) - 44.
Oláh T, Michaelis JC, Cai X, Cucchiarini M, Madry H. Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part II: Small animals. Ann Anat. 2021;234:151630 - 45.
Subbian S, Bandyopadhyay N, Tsenova L, O'Brien P, Khetani V, Kushner NL, et al. Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits. Cell Commun Signal. 2013;11:60 - 46.
Wu J, Xue J, Huang R, Zheng C, Cui Y, Rao S. A rabbit model of lumbar distraction spinal cord injury. Spine J. 2016;16(5):643-658 - 47.
Grilló MJ, Blasco JM, Gorvel JP, Moriyón I, Moreno E. What have we learned from brucellosis in the mouse model? Vet Res. 2012;43(1):29 - 48.
Denayer T, Stöhr T, Van Roy M. Animal models in translational medicine: Validation and prediction. New Horizons in Translational Medicine. 2014;2(1):5-11 - 49.
Mak IW, Evaniew N, Ghert M. Lost in translation: animal models and clinical trials in cancer treatment. (1943-8141 (Print)) - 50.
Sobajima S, Kompel Jf Fau - Kim JS, Kim Js Fau - Wallach CJ, Wallach Cj Fau - Robertson DD, Robertson Dd Fau - Vogt MT, Vogt Mt Fau - Kang JD, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. (1528-1159 (Electronic)) - 51.
Marques RM, Teixeira L Fau - Aguas AP, Aguas Ap Fau - Ribeiro JC, Ribeiro Jc Fau - Costa-e-Silva A, Costa-e-Silva A Fau - Ferreira PG, Ferreira PG. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD). (1297-9716 (Electronic)) - 52.
Neave MJ, Hall RA-O, Huang N, McColl KA, Kerr P, Hoehn M, et al. Robust Innate Immunity of Young Rabbits Mediates Resistance to Rabbit Hemorrhagic Disease Caused by Lagovirus Europaeus GI.1 But Not GI.2. LID - 10.3390/v10090512 [doi] LID - 512. (1999-4915 (Electronic)) - 53.
Trzeciak-Ryczek A, Tokarz-Deptuła B, Deptuła W. Expression of IL-1β, IL-2, IL-10, TNF-β and GM-CSF in peripheral blood leukocytes of rabbits experimentally infected with rabbit haemorrhagic disease virus. (1873-2542 (Electronic)) - 54.
Blasco JM. Brucella ovis. Animal brucellosis. 1990;8:9-12 - 55.
Blasco JM, Molina-Flores B. Control and eradication of Brucella melitensis infection in sheep and goats. Vet Clin North Am Food Anim Pract. 2011;27(1):95-104 - 56.
Garin-Bastuji B, Blasco JM, Marín C, Albert D. The diagnosis of brucellosis in sheep and goats, old and new tools. Small Ruminant Research. 2006;62(1):63-70 - 57.
Alhamada AG, Habib I, Barnes A, Robertson I. Risk Factors Associated with Brucella Seropositivity in Sheep and Goats in Duhok Province, Iraq. Veterinary sciences. 2017;4(4):65 - 58.
Oláh T, Cai X, Michaelis JC, Madry H. Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part I: Large animals. Ann Anat. 2021;235:151680 - 59.
Radwan AI, Bekairi SI, Mukayel AA. Treatment of Brucella melitensis infection in sheep and goats with oxytetracycline combined with streptomycin. Rev Sci Tech. 1992;11(3):845-857 - 60.
Wang F, Ni B, Zhu Z, Liu F, Zhu YZ, Liu J. Intra-discal vancomycin-loaded PLGA microsphere injection for MRSA discitis: an experimental study. Arch Orthop Trauma Surg. 2011;131(1):111-119 - 61.
Hull NC, Schumaker BA. Comparisons of brucellosis between human and veterinary medicine. Infect Ecol Epidemiol. 2018;8(1):1500846 - 62.
Prior S, Gander B, Lecároz C, Irache JM, Gamazo C. Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes. J Antimicrob Chemother. 2004;53(6):981-988 - 63.
Prior S, Gander B, Blarer N, Merkle HP, Subirá ML, Irache JM, et al. In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres. Eur J Pharm Sci. 2002;15(2):197-207 - 64.
Katonis P, Tzermiadianos M, Gikas A, Papagelopoulos P, Hadjipavlou A. Surgical treatment of spinal brucellosis. Clin Orthop Relat Res. 2006;444:66-72 - 65.
Bugybayeva D, Kydyrbayev Z, Zinina N, Assanzhanova N, Yespembetov B, Kozhamkulov Y, et al. A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization schedule in a guinea pig model. Infect Dis Poverty. 2021;10(1):13 - 66.
Hammami F, Koubaa M, Feki W, Chakroun A, Rekik K, Smaoui F, et al. Tuberculous and Brucellar Spondylodiscitis: Comparative Analysis of Clinical, Laboratory, and Radiological Features. Asian Spine J. 2020 - 67.
Unuvar GK, Kilic AU, Doganay M. Current therapeutic strategy in osteoarticular brucellosis. North Clin Istanb. 2019;6(4):415-420 - 68.
Liang C, Wei W, Liang X, De E, Zheng B. Spinal brucellosis in Hulunbuir, China, 2011-2016. Infect Drug Resist. 2019;12:1565-1571 - 69.
Zhang Y, Zhang Q, Zeng Z. Histopathological findings of nucleus pulposus in lumbar brucellar spondylodiscitis. Rev Soc Bras Med Trop. 2019;52:e20180108 - 70.
Lee H, Hur J, Lee J, Lee S. Brucellar Spondylitis. Journal of Korean Neurosurgical Society. 2008;44:277-279 - 71.
Zileli M, Ebeoglu A. Brucellar spondylodiscitis. ArgoSpine News & Journal. 2011;23 - 72.
Zhang N, Fang M, Chen H, Gou F, Ding M. Evaluation of spinal cord injury animal models. Neural Regen Res. 2014;9(22):2008-2012 - 73.
Sheng SR, Wang XY, Xu HZ, Zhu GQ, Zhou YF. Anatomy of large animal spines and its comparison to the human spine: a systematic review. Eur Spine J. 2010;19(1):46-56 - 74.
Zhang Y. Animal models of inflammatory spinal and sacroiliac joint diseases. Rheum Dis Clin North Am. 2003;29(3):631-645