Effect of chondroitinase ABC on inflammatory and oxidative response following spinal cord injury

Document Type : Original Article


1 Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

2 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Faculty of Veterinary Medicine, Shahid Bahonar University, Kerman, Iran

4 Department of Biostatistics and Epidemiology, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran

5 Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran


Objective(s): Chondroitinase ABC (cABC) treatment improves functional recovery following spinal cord injury (SCI) through degrading inhibitory molecules to axon growth. However, cABC involvement in other pathological processes contributing to SCI remains to be investigated. Here, we studied the effect of cABC I on oxidative stress and inflammation developed in a rat model of SCI.
Materials and Methods: Male rats (220–250 g) were divided into three groups (n=28) including rats that underwent SCI (SCI group), rats subjected to SCI and received an intrathecal injection of phosphate buffer saline (SCI+PBS group), and rats that underwent SCI and received cABC intrathecally (SCI+E group). Then, the level of TNF-α, Il-1β, malondialdehyde, nitric oxide, and myeloperoxidase in injured tissues, as well as hindlimb motor function, were measured at 4 hr, 1, 3 and 7 days post-SCI.
Results: Our data showed that cABC treatment reduced the development of inflammation and oxidative stress associated with SCI at all-time points. In addition, functional recovery was improved in rats that received cABC at 7 days post-SCI.
Conclusion: The present findings indicate that cABC treatment can exert its neuroprotective effect through modulation of post-traumatic inflammatory and oxidative response.


1. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 2011; 71: 281-299.
2.   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.
3.   Chan CC. Inflammation: beneficial or detrimental after spinal cord injury? Recent Pat CNS Drug Discov 2008; 3: 189-199.
4.   McPhail LT, Stirling DP, Tetzlaff W, Kwiecien JM, Ramer MS. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury. Eur J Neurosci 2004; 20: 1984-1994.
5.   Fitch MT, Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Exp Neurol 1997; 148: 587-603.
6.   Hausmann ON. Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003; 41: 369-378.
7.   Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007; 87: 315-424.
8.   Pannu R, Barbosa E, Singh AK, Singh I. Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res 2005; 79: 340-350.
9.   James ND, Shea J, Muir EM, Verhaagen J, Schneider BL, Bradbury EJ. Chondroitinase gene therapy improves upper limb function following cervical contusion injury. Exp Neurol 2015; 271: 131-135.
10. Kwok JC, Afshari F, Garcia-Alias G, Fawcett JW. Proteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC. Restor Neurol Neurosci 2008; 26: 131-145.
11. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636-640.
12. Rolls A, Cahalon L, Bakalash S, Avidan H, Lider O, Schwartz M. A sulfated disaccharide derived from chondroitin sulfate proteoglycan protects against inflammation-associated neurodegeneration. FASEB J 2006; 20: 547-549.
13. Barritt AW, Davies M, Marchand F, Hartley R, Grist J, Yip P et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 2006; 26: 10856-10867.
14. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995; 12: 1-21.
15. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990; 186: 407-421.
16. Taskiran D, Kutay FZ, Sozmen E, Pogun S. Sex differences in nitrite/nitrate levels and antioxidant defense in rat brain. Neuroreport 1997; 8: 881-884.
17. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78: 206-209.
18. Popovich PG, Jones TB. Manipulating neuroinflamma-tory reactions in the injured spinal cord: back to basics. Trends Pharmacol Sci 2003; 24: 13-17.
19. Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. Acute inflammatory response in spinal cord following impact injury. Exp Neurol 1998; 151: 77-88.
20. Popovich PG, Guan Z, McGaughy V, Fisher L, Hickey WF, Basso DM. The neuropathological and behavioral consequen-ces of intraspinal microglial/macrophage activation. J Neuro-pathol Exp Neurol 2002; 61: 623-633.
21. Streit WJ, Semple-Rowland SL, Hurley SD, Miller RC, Popovich PG, Stokes BT. Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp Neurol 1998; 152: 74-87.
22. Aimone JB, Leasure JL, Perreau VM, Thallmair M. Spatial and temporal gene expression profiling of the contused rat spinal cord. Exp Neurol 2004; 189: 204-221.
23. Ramer LM, Ramer MS, Bradbury EJ. Restoring function after spinal cord injury: towards clinical translation of experimental strategies. Lancet Neurol 2014; 13: 1241-1256.
24. Rolls A, Avidan H, Cahalon L, Schori H, Bakalash S, Litvak V et al. A disaccharide derived from chondroitin sulphate proteoglycan promotes central nervous system repair in rats and mice. Eur J Neurosci 2004; 20: 1973-1983.
25. Didangelos A, Iberl M, Vinsland E, Bartus K, Bradbury EJ. Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury. J Neurosci 2014; 34: 16424-16432.
26. Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma 2000; 17: 871-890.
27. Leski ML, Bao F, Wu L, Qian H, Sun D, Liu D. Protein and DNA oxidation in spinal injury: neurofilaments--an oxidation target. Free Radic Biol Med 2001; 30: 613-624.
28. Qian H, Liu D. The time course of malondialdehyde production following impact injury to rat spinal cord as measured by microdialysis and high pressure liquid chromatography. Neurochem Res 1997; 22: 1231-1236.
29. Vaishnav RA, Singh IN, Miller DM, Hall ED. Lipid peroxidation-derived reactive aldehydes directly and differentially impair spinal cord and brain mitochondrial function. J Neurotrauma 2010; 27: 1311-1320.
30. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol 2013; 698: 6-18.
31. Bao F, Liu D. Peroxynitrite generated in the rat spinal cord induces neuron death and neurological deficits. Neuroscience 2002; 115: 839-849.
32. Matsuyama Y, Sato K, Kamiya M, Yano J, Iwata H, Isobe K. Nitric oxide: a possible etiologic factor in spinal cord cavitation. J Spinal Disord 1998; 11: 248-252.
33. Biagas KV, Uhl MW, Schiding JK, Nemoto EM, Kochanek PM. Assessment of posttraumatic polymorphonuclear leukocyte accumulation in rat brain using tissue myeloperoxidase assay and vinblastine treatment. J Neurotrauma 1992; 9: 363-371.
34. Panasenko OM, Evgina SA, Driomina ES, Sharov VS, Sergienko VI, Vladimirov YA. Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid liposomes. Free Radic Biol Med 1995; 19: 133-140.
35. Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW.
Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 2009; 12: 1145-1151.
36. Zuo J, Neubauer D, Dyess K, Ferguson TA, Muir D. Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue. Exp Neurol 1998; 154: 654-662.
37. Blight AR. Macrophages and inflammatory damage in spinal cord injury. J Neurotrauma 1992; 9 Suppl 1: S83-91.