Iran J Vet Surg, Print ISSN: 2008-3033, Online ISSN: 2676-6299

Document Type : Original Article


1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran

2 Department of Pathobiology, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran

3 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium


Objective- The current study was conducted to evaluate changes in the urinary bladder structure and leukocyte profile as an important index of the systemic inflammation response for two different types of spinal cord injury (SCI) in a rat model.
Design- Experimental Study.
Animals- Forty adult healthy female Sprague-Dawley rats.
Procedure- Animals were assigned into two equal model groups: the incomplete transection group (ITG) and the contusion group (CG). In both groups, SCI was created at the T9-10 level of the column. Alterations in the urinary bladder construction and changes in the leukocytes were examined in both groups post-surgically.
Results- Degenerative changes and a reduction in the cellular volume in the mucous layer, hyperemia, and the presence of inflammatory cells in the submucosa were the most important findings in both SCI groups. The extent of the destructive lesions was more prominent in the CG 14 days after operation. At 28 days after surgery, pathological lesions including leukocyte infiltration in the submucosa, denudation of the urothelial mucosa, severe edema, atrophy of the muscle layer, and necrosis of muscle fibers in some areas were recorded in both groups; the extent and severity of the lesions were more evident in the CG. There was no significant difference between the white blood cells and N/L ratio at the different times in the CG and ITG groups.
Conclusion and Clinical Relevance- Despite the similar leukocyte response in the IGT and CG, more severe degenerative histological alternations in the urinary bladder structure were observed in the CG. Therefore, attention should be paid to the extent of cystitis in these patients in clinical trials and interventions.


Main Subjects

  1. Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Advances in Physiology Education, 2002; 26(4): 238-255.
  2. Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. Mary Ann Liebert, Inc., 2004.
  3. Herrera JJ, Haywood-Watson RJ, Grill RJ. Acute and chronic deficits in the urinary bladder after spinal contusion injury in the adult rat. Journal of Neurotrauma, 2010; 27(2): 423-431.
  4. Yu X, Xu L, Zhang X, Cui F. Effect of spinal cord injury on urinary bladder spinal neural pathway: a retrograde transneuronal tracing study with pseudorabies virus. Urology, 2003; 62(4): 755-759.
  5. Craggs MD, Balasubramaniam AV, Chung EA, Emmanuel AV. Aberrant reflexes and function of the pelvic organs following spinal cord injury in man. Autonomic Neuroscience, 2006; 126: 355-370.
  6. Samson G, Cardenas DD. Neurogenic bladder in spinal cord injury. Physical Medicine and Rehabilitation Clinics of North America, 2007; 18(2): 255-274.
  7. Apodaca G, Kiss S, Ruiz W, Meyers S, Zeidel M, Birder L. Disruption of bladder epithelium barrier function after spinal cord injury. American Journal of Physiology-Renal Physiology, 2003; 284(5): F966-F976.
  8. Toosi KK, Nagatomi J, Chancellor MB, Sacks MS. The effects of long-term spinal cord injury on mechanical properties of the rat urinary bladder. Annals of Biomedical Engineering, 2008; 36(9): 1470-1480.
  9. Janzen J, Bersch U, Pietsch-Breitfeld B, Pressler H, Michel D, Bültmann B. Urinary bladder biopsies in spinal cord injured patients. Spinal Cord, 2001; 39(11): 568.
  10. Janzen J, Vuong P, Bersch U, Michel D, Zaech G. Bladder tissue biopsies in spinal cord injured patients: histopathologic aspects of 61 cases. Neurourology and Urodynamics, 1998; 17(5): 525-530.
  11. Genovese T, Esposito E, Mazzon E, Di Paola R, Caminiti R, Bramanti P, Cappelani A, Cuzzocrea S. Absence of endogenous interleukin‐10 enhances secondary inflammatory process after spinal cord compression injury in mice. Journal of Neurochemistry, 2009; 108(6): 1360-1372.
  12. Okada S. The pathophysiological role of acute inflammation after spinal cord injury. Inflammation and Regeneration, 2016; 36(1): 20.
  13. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y1, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 2018; 9(6): 7204.
  14. Trivedi A, Olivas AD, Noble-Haeusslein LJ. Inflammation and spinal cord injury: infiltrating leukocytes as determinants of injury and repair processes. Clinical Neuroscience Research, 2006; 6(5): 283-292.
  15. Kwon BK, Oxland TR, Tetzlaff W. Animal models used in spinal cord regeneration research. Spine, 2002; 27(14): 1504-1510.
  16. Onifer SM, Rabchevsky AG, Scheff SW. Rat models of traumatic spinal cord injury to assess motor recovery. ILAR Journal, 2007; 48(4): 385-395.
  17. Verma R, Virdi JK, Singh N, Jaggi AS. Animals models of spinal cord contusion injury. Korean Journal of Pain, 2019; 32(1): 12-21.
  18. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science, 2011; 25: 331:1565-1570.
  19. Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, Widmann WD. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Annals of Surgical Oncology, 2012; 19(1): 217-224.
  20. Swan MP, Hickman DL. Evaluation of the neutrophil-lymphocyte ratio as a measure of distress in rats. Laboratory Animals, 2014; 43(8): 276-282.
  21. Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. Journal of Surgical Oncology, 2005; 1: 91(3): 181-184.
  22. Malik HZ, Prasad KR, Halazun KJ, Aldoori A, Al-Mukhtar A, Gomez D, Lodge JP, Toogood GJ. Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases. Annals of Surgery, 2007; 246(5): 806-814.
  23. Davis AK, Maney DL, Maerz JC. The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists. Functional Ecology, 2008; 22: 760–772.
  24. Blumenreich MS. The White Blood Cell and Differential Count. Kenneth WH, Hall WD, Hurst JW. In: eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, Butterworths, 1990.
  25. Bain BJ. Briggs C. Laffan MA. Dacie and Lewis Practical Haematology. 12th ed. Elsevier, 2017.
  26. Leary SL, Underwood W, Anthony R, Gwaltney-Brant S, Poison A, Meyer R, editors. AVMA guidelines for the euthanasia of animals. American Veterinary Medical Association Schaumburg, IL, 2013.
  27. Hung E, Darouiche R, Trautner B. Proteus bacteriuria is associated with significant morbidity in spinal cord injury. Spinal cord, 2007; 45(9): 616.
  28. Acharya P, Beckel J, Ruiz WG, Wang E, Rojas R, Birder L, Apodaca G. Distribution of the tight junction proteins ZO-1, occludin, and claudin-4,-8, and-12 in bladder epithelium. American Journal of Physiology-Renal Physiology, 2004; 287(2): F305-F318.
  29. Al Taweel W, Seyam R. Neurogenic bladder in spinal cord injury patients. Research and Reports in Urology, 2015; 7: 85.
  30. Friedli L, Rosenzweig ES, Barraud Q, Schubert M, Dominici N, Awai L, Nielson JL, Musienko P, Nout-Lomas Y, Zhong H, Zdunowski S, Roy RR, Strand SC, van den Brand R, Havton LA, Beattie MS, Bresnahan JC, Bézard E, Bloch J, Edgerton VR, Ferguson AR, Curt A, Tuszynski MH, Courtine G. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates. Science Translational Medicine,2015; 7(302): 302ra134.
  31. Kjell J, Olson L. Rat models of spinal cord injury: from pathology to potential therapies. Disease Models and Mechanisms, 2016; 9(10): 1125-1137.
  32. Bao F, Bailey CS, Gurr KR, Bailey SI, Rosas-Arellano MP, Dekaban GA, Weaver LC. Increased oxidative activity in human blood neutrophils and monocytes after spinal cord injury. Experimental Neurology, 2009; 215(2): 308-316.
  33. Sun X, Jones ZB, Chen X-m, Zhou L, So K-F, Ren Y. Multiple organ dysfunction and systemic inflammation after spinal cord injury: a complex relationship. Journal of Neuroinflammation, 2016; 13(1): 260.
  34. Javdani M, Habibi A, Shirian S, Kojouri GA, Hosseini F. Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats. Biological Trace Element Research, 2019; 187(1): 202-211.
  35. Al-Hussain F, Alfallaj MM, Alahmari AN, Almazyad AN, Alsaeed TK, Abdurrahman AA, Murtaza G, Bashir S. Relationship between Neutrophil-to-Lymphocyte Ratio and Stress in Multiple Sclerosis Patients. Journal of Clinical and Diagnostic Research, 2017; 11(5): CC01.
  36. Neirinckx V, Coste C, Franzen R, Gothot A, Rogister B, Wislet S. Neutrophil contribution to spinal cord injury and repair. Journal of Neuroinflammation, 2014; 11(1): 150.