Prognostic factors of neuroinflammation and oxidative stress in brain injury patients at Cipto Mangunkusumo Hospital Jakarta

  • Renindra A. Aman
  • Syaiful Ichwan
  • Alida Harahap
  • Yusuf Wibisono
  • Nia Yuliatri
  • Mohammad A. Aulia
  • Hans-Joachim Freisleben
Keywords: Neuroinflammation, oxidative stress, traumatic brain injury, neurosurgical procedures, interleukin 6, uric acid, malondialdehyde, NR2A antibody, glutathione
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Background: This study aims to determine the association between neuroinflammation and oxidative stress with prognosis of brain injury patients and the association between neurosurgical procedure with neuroinflammation and oxidative stress condititons.

Methods: The study design is a prospective observation of 40 brain injury patients who underwent surgery. IL-6, uric acid, MDA, NR2A antibodies and GSH serum level of pre- and 1 day post-operation on brain injury patients were measured, and their association with GCS, GOS and neurosurgical procedures were analyzed.

Results: The post-operative IL-6 serum level showed a downward trend compared to pre-operative value (mean decrease: -190.61 pg/mL). The post-operative IL-6 level was significantly associated with GCS 7 days post-operation (p = 0.006), with OR 24. The post-operative IL-6 serum level was significantly associated with GOS 3 months post-trauma (p = 0.016) with OR 11.6. The post-operative uric acid serum level showed a downward trend compared to pre-operative value (mean decrease: -0.26 mg/dL). There was a significant difference between the mean value of post-operative uric acid serum level in patients with 7 days post-trauma with GCS ⤠8 (mean: 4.16 mg/dL) and GCS > 8 (mean: 2.71 mg/dL), (p = 0.042). The post-operative MDA serum level showed a downward trend compared to pre-operative value (mean decrease: -0.08 nmol/mL). There is no significant association between MDA serum level, GCS and GOS and no significant association of NR2A antibody and GSH serum level with GCS, GOS and neurosurgical procedure. From the multivariate analysis, the most important neuroinflammatory variable associated with GCS and GOS is IL-6.

Conclusion: Neuroinflammation and oxidative stress may have prognostic values in brain-injured patients, in particular IL-6. Neurosurgical procedures may decrease the neuroinflammation process (Med J Indones. 2012;21:152-9)


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  1. Selladurai B, Reilly P, editors. Initial management of head injury: a comprehensive guide. Brisbane: McGraw-Hill Australia Pty Ltd; 2007. p. 1-28.

  2. Longhi L, Saatman K. Cellular basic of injury and recovery from trauma. In: Winn HR, editor. Youmans neurological surgery. Philadelphia: Saunders; 1996. p. 5025-33.

  3. Zwienenberf-Lee M, Muizelaar JP. Clinical pathophysiology of traumatic brain injury. In: Winn HR, editor. Youmans neurological surgery. Philadelphia: Saunders; 1996. p. 5039-58.

  4. Woicienchowxky C, Schoning B, Cobanov J, Lanksch WR, Volk HD, Docke WD. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma. 2002;52:339-45.

  5. Swartz KR, Liu F, Sewell D, Schocet T, Campbell I, Sandor M, et al. Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res. 2001;896:86-95.

  6. Schmidt OI, Infanger M, Heyde CE, Ertel W, Stahel F. The role of neuroinflammation in traumatic brain injury. Eur J Trauma. 2004;30:135-49.

  7. Bayir H, Kagan VE. Bench-to-bedside review: mitochondrial injury, oxidative stress and apoptosis – there is nothing more practical than a good theory. Crit Care. 2008;12:206.

  8. Higgins P, Walters M, Dawson J. The potential for xanthine oxidase inhibition in the prevention and treatment of cardiovascular and cerebrovascular disease. Cardiovascular Psychiatry and Neurology. 2009, Article ID 282059.

  9. Paolin A, Nardin L, Gaetani P, Rodriguez Y, Baena R, Pansarasa O, et al. Oxidative damage after severe head injury and its relationship to neurological outcome. Neurosurgery. 2002;51:949-55.

  10. Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem. 2000;267:4912-6.

  11. Townsend DT, Tew KD, Tapiero AH. The importance of glutathione in human disease. Biomed Pharmacother. 2003;57:145-55.

  12. Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. 2006;37:1432-6.

  13. Bullock MR, Chesnut R, Ghajar J, Gordon D, Servadei F, Hartl R, et al. Guidelines for the surgical management of traumatic brain injury. Neurosurgery. 2006;58(3):1-57.

  14. Badiyono B, Moeslichan S, Sastroasmoro S, Budiman I, Purwanto H. Perkiraan besar sampel. Dasar-dasar metodologi penelitian klinis. Jakarta: Sagung Seto; 2002. p. 259-86. Indonesian.

  15. Baldwin SA, Fugaccia I, Brown DR, Brown LV, Scheff SW. Blood-brain barrier breach following cortical contusion in the rat. J Neurosurg. 1996;85:476–81.

  16. Hergenroeder GW, Moore AN, McCoy JP, Samsel W, Ward NH, Clifton GL, et al. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury. J Neuroinflammation. 2010;7:19.

  17. Kinuta Y, Kimura M, Itokawa Y, Ishikawa M, Kikuchi H. Changes in xanthine oxidase in ischemic rat brain. J Neurosurg. 1989;71:417-20.

  18. Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006;58(1):87-114.

  19. Ayer RE, Zhang JH. Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm.Acta Neurochir Suppl. 2008;104:33-41.

  20. Sloan J, Symonds T, Vargas-Chanes D, Fridley B. Practical guidelines for assessing the clinical significance of health-related quality of life changes within clinical trials. Drug Information Journal. 2003;37:23-31.

  21. Shohami E, Gati I, Beit-Yannai E, Trembovler V, Kohen R. Closed head injury in the rat induces whole body oxidative stress: overall reducing antioxidant profile. J Neurotrauma. 1999;16:365-76.

  22. Shohami E, Beit-Yannai E, Horowitz M, Kohen R. Oxidative stress in closed-head injury: brain antioxidant capacity as an indicator of functional outcome. J Cereb Blood Flow Metab. 1997;17:1007-19.

  23. Bullock MR, Merchant RE, Choi SC, Gilman CB, Kreutzer JS, Marmarou A, et al. Outcome measures for clinical trials in neurotrauma. Neurosurg Focus. 2002;13:1-11.

  24. Brennan AM, Suh SW, Won SJ, Narasimhan P, Kauppinen TM, Lee H, et al. NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci. 2009;12(7):857-63.

  25. Papadia S, Hardingham GE. The dichotomy of NMDA receptor signaling. Neuroscientist. 2007;13(6):572-9.

  26. Dambinova SA, Khounteev GA, Izykenova GA, Zavolokov IG, Ilyukhina AY, Skoromets AA. Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem. 2003;49(10):1752-62.

  27. Kudo H, Mio T, Kokunai T, Tamaki N, Sumino K, Matsumoto S. Quantitative analysis of glutathione in human brain tumors. J Neurosurg. 1990;72:610-5.

How to Cite
Aman RA, Ichwan S, Harahap A, Wibisono Y, Yuliatri N, Aulia MA, Freisleben H-J. Prognostic factors of neuroinflammation and oxidative stress in brain injury patients at Cipto Mangunkusumo Hospital Jakarta. Med J Indones [Internet]. 2012Aug.1 [cited 2024Jun.20];21(3):152-9. Available from:
Clinical Research

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