Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

Document Type : Original Article


1 Department of Spine Surgery, Aviation General Hospital of China Medical University, Beijing Institute of Translational Medicine, Chinese Academy of Sciences, No. 3 Anwai beiyuan Road, Chaoyang District, Beijing, 100012, China

2 Department of Neurology, Beijing Tsinghua Changgung Hospital Medical Center, Tsinghua University, No. 168 Li Tang Rd. Dongxiaokou Town, Tiantongyuan Area, Changping District, Beijing, 102218, China


Objective(s): To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection
Materials and Methods:Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry.
Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly  decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery.
Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.


1. Ide C. Peripheral nerve regeneration. Neurosci Res 1996; 25:101-121.
2. Karanth S, Yang G, Yeh J, Richardson PM. Nature of signals that initiate the immune response during Wallerian degeneration of peripheral nerves. Exp Neurol 2006; 202:161-166.
3. Nguyen MD, Julien JP, Rivest S. Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 2002; 3:216-227.
4. Tuszynski MH, Steward O. Concepts and methods for the study of axonal regeneration in the CNS. Neuron 2012; 74:777-791.
5. Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol 2004; 5:575-581.
6. Profyris C, Cheema SS, Zang D, Azari MF, Boyle K, Petratos S. Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 2004; 15:415-436.
7. Camara-Lemarroy CR, Guzman-de la Garza FJ, Fernandez-Garza NE. Molecular inflammatory mediators in peripheral nerve degeneration and regeneration. Neuroimmunomodulation 2010; 17:314-324.
8. Ha GK, Parikh S, Huang Z, Petitto JM. Influence of injury severity on the rate and magnitude of the T lymphocyte and neuronal response to facial nerve axotomy. J Neuroimmunol 2008; 199:18-23.
9. Temporin K, Tanaka H, Kuroda Y, Okada K, Yachi K, Moritomo H, et al. Interleukin-1 beta promotes sensory nerve regeneration after sciatic nerve injury. Neurosci Lett 2008; 440:130-133.
10. Amadori A, Zamarchi R, De Silvestro G, Forza G, Cavatton G, Danieli GA, et al. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med 1995; 1:1279-1283.
11. Shokouhi G, Tubbs RS, Shoja MM, Hadidchi S, Ghorbanihaghjo A, Roshangar L, et al. Neuroprotective effects of high-dose vs low dose melatonin after blunt sciatic nerve injury. Childs Nerv Syst 2008; 24:111–117.
12. Chlebicki CA, et al. The sciatic nerve transection in the third treatment group was performed by severing the left sciatic nerve with a scalpel. Lasers Surg Med 2010; 42:306–312.
13. Blackburn GL. Metabolic considerations in management of surgical patients. Surg Clin North Am 2011; 91:467-480.
14. Duarte-Rey C, Bogdanos DP, Leung PS, Anaya JM, Gershwin ME. IgM predominance in autoimmune disease: genetics and gender. Autoimmun Rev 2012; 11:A404-412.
15. Torgerson TR. Overview of routes of IgG administration. J Clin Immunol 2013; 33:S87-89.
16. Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation 2011; 8:110.
17. Tian P, et al.  Orthop Surg 2009; 1, 4: 317–321.
18. Hendriks JJ, Teunissen CE, de Vries HE, Dijkstra CD. Macrophages and neurodegeneration. Brain Res Brain Res Rev 2005; 48:185-195.
19. Koeppen AH. Wallerian degeneration: history and clinical significance. J Neurol Sci 2004; 220:115-117.
20. Zochodne DW. The microenvironment of injured and regenerating peripheral nerves. Muscle Nerve Suppl 2000; 9:S33-38.