J Korean Neurosurg Soc.  2015 Feb;57(2):73-76. 10.3340/jkns.2015.57.2.73.

Effects of Tumor Necrosis Factor Alpha Blocker Adalimumab in Experimental Spinal Cord Injury

Affiliations
  • 1Department of Neurosurgery, Gazi University Faculty of Medicine, Ankara, Turkey. alpborcek@gmail.com
  • 2Department of Neurosurgery, Medicana Private Hospital, Konya, Turkey.
  • 3Department of Biochemistry, Gazi University Faculty of Medicine, Ankara, Turkey.

Abstract


OBJECTIVE
Tumor necrosis factor alpha (TNF-alpha) have proven effects in pathogenesis of neuroinflammation after spinal cord injury (SCI). Current study is designed to evaluate the effects of an anti-TNF-alpha agent, adalimumab, on spinal cord clip compression injury in rats.
METHODS
Thirty two male adult Wistar rats were divided into four groups (sham, trauma, infliximab, and adalimumab groups) and SCI was introduced using an aneurysm clip. Animals in treatment groups received 5 mg/kg subcutaneous adalimumab and infliximab right after the trauma. Malondialdehyde (MDA) levels were studied in traumatized spinal cord tissues 72 hours after the injury as a marker of lipid peroxidation.
RESULTS
Animals that received anti-TNF-alpha agents are found to have significantly decreased MDA levels. MDA levels were significantly different between the trauma and infliximab groups (p<0.01) and trauma and adalimumab groups (p=0.022). There was no significant difference in neurological evaluation of the rats using Tarlov scale.
CONCLUSION
These results suggest that, like infliximab, adalimumab has favorable effects on lipid peroxidation induced by spinal cord trauma in rats.

Keyword

Adalimumab; Spinal cord injury; Tumor necrosis factor alpha

MeSH Terms

Adult
Aneurysm
Animals
Humans
Lipid Peroxidation
Male
Malondialdehyde
Rats
Rats, Wistar
Spinal Cord
Spinal Cord Injuries*
Tumor Necrosis Factor-alpha*
Adalimumab
Infliximab
Malondialdehyde
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 Box plot demonstrating mean MDA levels. MDA levels were significantly different between the trauma and infliximab groups (theta, p<0.01) and trauma and adalimumab groups (asterisk, p=0.022) (central line for each group indicates median, with the box showing upper and lower quartiles and the whiskers showing the range). MDA : malondialdehyde

  • Fig. 2 Line graph demonstrating progress in mean Tarlov scores in groups.


Reference

1. Balentine JD. Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest. 1978; 39:236–253. PMID: 713489.
2. Balentine JD. Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Lab Invest. 1978; 39:254–266. PMID: 713490.
3. Bayrakli F, Balaban H, Ozum U, Duger C, Topaktas S, Kars HZ. Etanercept treatment enhances clinical and neuroelectrophysiological recovery in partial spinal cord injury. Eur Spine J. 2012; 21:2588–2593. PMID: 22526707.
Article
4. Beattie MS, Hermann GE, Rogers RC, Bresnahan JC. Cell death in models of spinal cord injury. Prog Brain Res. 2002; 137:37–47. PMID: 12440358.
5. Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, Marcillo AE, et al. Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma. 1999; 16:851–863. PMID: 10547095.
Article
6. Blight AR. Macrophages and inflammatory damage in spinal cord injury. J Neurotrauma. 1992; 9(Suppl 1):S83–S91. PMID: 1588634.
7. Bracken MB. Methylprednisolone and acute spinal cord injury : an update of the randomized evidence. Spine (Phila Pa 1976). 2001; 26(24 Suppl):S47–S54. PMID: 11805609.
8. Bracken MB. Methylprednisolone in the management of acute spinal cord injuries. Med J Aust. 1990; 153:368. PMID: 2233469.
Article
9. Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev. 2012; 1:CD001046. PMID: 22258943.
Article
10. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA. 1984; 251:45–52. PMID: 6361287.
Article
11. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990; 322:1405–1411. PMID: 2278545.
Article
12. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, Freeman DF, et al. Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J Neurosurg. 1985; 63:704–713. PMID: 3903070.
Article
13. Burmester GR, Mease P, Dijkmans BA, Gordon K, Lovell D, Panaccione R, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009; 68:1863–1869. PMID: 19147611.
Article
14. Burness CB, Keating GM. Adalimumab : a review of its use in the treatment of patients with ulcerative colitis. BioDrugs. 2013; 27:247–262. PMID: 23580096.
Article
15. Caminero A, Comabella M, Montalban X. Tumor necrosis factor alpha (TNF-α), anti-TNF-α and demyelination revisited: an ongoing story. J Neuroimmunol. 2011; 234:1–6. PMID: 21474190.
Article
16. 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. PMID: 9582256.
Article
17. Catalá A. Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions. Chem Phys Lipids. 2009; 157:1–11. PMID: 18977338.
Article
18. Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A. Tumor necrosis factor alpha blockers and malignancy in children : forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum. 2010; 62:2517–2524. PMID: 20506368.
Article
19. Ducker TB, Kindt GW, Kempf LG. Pathological findings in acute experimental spinal cord trauma. J Neurosurg. 1971; 35:700–708. PMID: 5000662.
Article
20. Emmez H, Börcek AÖ, Kaymaz M, Kaymaz F, Durdağ E, Civi S, et al. Neuroprotective effects of gabapentin in experimental spinal cord injury. World Neurosurg. 2010; 73:729–734. PMID: 20934165.
Article
21. Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD, et al. The cellular inflammatory response in human spinal cords after injury. Brain. 2006; 129(Pt 12):3249–3269. PMID: 17071951.
Article
22. Grotto D, Maria LS, Valentini J, Paniz C, Schmitt G, Garcia SC, et al. Importance of the lipid peroxidation biomarkers and methodological aspects for malondialdehyde quantification. Quim Nova. 2009; 32:169–174.
Article
23. Guadagno J, Xu X, Karajgikar M, Brown A, Cregan SP. Microglia-derived TNFα induces apoptosis in neural precursor cells via transcriptional activation of the Bcl-2 family member Puma. Cell Death Dis. 2013; 4:e538. PMID: 23492769.
Article
24. Guven C, Borcek AO, Cemil B, Kurt G, Yildirim Z, Ucankus NL, et al. Neuroprotective effects of infliximab in experimental spinal cord ischemic injury. J Clin Neurosci. 2010; 17:1563–1567. PMID: 20817464.
Article
25. Hall ED. Inhibition of lipid peroxidation in CNS trauma. J Neurotrauma. 1991; 8(Suppl 1):S31–S40. discussion S41. PMID: 1920459.
26. Hall ED, Braughler JM. Free radicals in CNS injury. Res Publ Assoc Res Nerv Ment Dis. 1993; 71:81–105. PMID: 8380240.
27. Hamada Y, Ikata T, Katoh S, Nakauchi K, Niwa M, Kawai Y, et al. Involvement of an intercellular adhesion molecule 1-dependent pathway in the pathogenesis of secondary changes after spinal cord injury in rats. J Neurochem. 1996; 66:1525–1531. PMID: 8627308.
Article
28. Harrington JF, Messier AA, Levine A, Szmydynger-Chodobska J, Chodobski A. Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord injury. J Neurotrauma. 2005; 22:919–928. PMID: 16083358.
Article
29. Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK, et al. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol. 2009; 131:308–316. PMID: 19188093.
Article
30. Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, et al. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986; 136:4220–4225. PMID: 3009619.
31. Kurt G, Cemil B, Borcek AO, Borcek P, Akyurek N, Sepici A, et al. Infliximab administration reduces neuronal apoptosis on the optic pathways in a rabbit hydrocephalus model : a preliminary report. Br J Neurosurg. 2010; 24:275–279. PMID: 20465456.
32. Kurt G, Ergün E, Cemil B, Börcek AO, Börcek P, Gülbahar O, et al. Neuroprotective effects of infliximab in experimental spinal cord injury. Surg Neurol. 2009; 71:332–336. PMID: 18440605.
Article
33. Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 2011; 28:1545–1588. PMID: 20146558.
Article
34. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86:271–278. PMID: 655387.
Article
35. Papakostas JC, Matsagas MI, Toumpoulis IK, Malamou-Mitsi VD, Pappa LS, Gkrepi C, et al. Evolution of spinal cord injury in a porcine model of prolonged aortic occlusion. J Surg Res. 2006; 133:159–166. PMID: 16337967.
Article
36. Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis : results of a randomised controlled trial. Gut. 2011; 60:780–787. PMID: 21209123.
Article
37. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976). 2001; (24 Suppl):S2–S12. PMID: 11805601.
Article
38. Tang X, Wang Y, Zhou S, Qian T, Gu X. Signaling pathways regulating dose-dependent dual effects of TNF-α on primary cultured Schwann cells. Mol Cell Biochem. 2013; 378:237–246. PMID: 23479382.
Article
39. Wang CX, Nuttin B, Heremans H, Dom R, Gybels J. Production of tumor necrosis factor in spinal cord following traumatic injury in rats. J Neuroimmunol. 1996; 69:151–156. PMID: 8823387.
Article
40. Yu SH, Cho DC, Kim KT, Nam KH, Cho HJ, Sung JK. The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury. J Korean Neurosurg Soc. 2012; 51:191–198. PMID: 22737297.
Article
Full Text Links
  • JKNS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr