Travmatik Beyin Hasarında İnflamatuvar Sitokinlerin Rolü

Abstract

Travmatik beyin hasarı dünyada, 45 yaş altı bireylerde mortalite ve morbiditenin başlıca nedenlerinden biridir. Oluşan bu birincil lezyonlardan daha çok, esas olarak, bu direkt etkinin başlattığı ikincil süreç, mortalite ve morbiditeden sorumludur ve teröpatik müdahalelere de duyarlıdır. Birincil ve ikincil patofizyolojik süreçlerin her ikisi de hücresel mediatörlerin (proinflamatuvar sitokinler, prostaglandinler, serbest radikaller ve komplemanlar) salınımına, adezyon moleküllerinin ekspresyonuna, savunma ve glial hücrelerinin kemotaksisine ve transmigrasyonuna neden olmaktadır. Travmatik beyin hasarından sonra proinflamatuvar sitokinlerin üretimi ve sekresyonu hem insan hem de deneysel hayvan modellerinde gösterilmiştir. Beyinde travmadan sonra interlökin 1, interlökin 6, tümör nekroz faktör ve santral sinir sistemi kaynaklı sitokinlerin yüksek konsantrasyonlarda saptanması onların travmayı takiben gelişen patolojik süreçte önemli rol oynadıklarını düşündürmektedir. Bu sitokinlerinlerin hasar sürecinde oynadığı rolü bilmek ve geliştirilecek uygun ajanlar ile kendi kendine ilerleyici bu süreci bir noktada durdurmak yani nöronal hasarı azaltmak, kafa travmasında hayat kurtarıcı olabilir.

Keywords

• Travmatik beyin hasarı, İnterlökin-1, İnterlökin-6, Tümörnekroz faktör alfa

References

1. 1. Werner CK. Engelhard. Pathophysiology of traumatic brain injury. Br J Anaesth 2007;99:4-9. doi:10.1093/bja/aem131
2. 2. Marx J (editor). Rosen’s Emergency Medicine and Clinical Practice. 7th Edition. Philedelphia: Mosby, Elsevier, 2010:297-9.
3. 3. Frugier T, Morganti-Kossmann MC, O'Reilly D, McLean CA. J Neurotrauma 2010, 27: 497-507. doi:10.1089/neu.2009.1120.
4. 4. Schmidek HH, Roberts DW (editors). Schmidek and Sweet Operative Neurosurgical Techniques: Indications, Methods and Results. 5th. edition. Philedelphia: WB Saunders, 2005: 32-4.
5. 5. Youmans JR. (editor) Neurological Surgery. 6th. edition. Philedelphia:Saunders, 2011: 3277-80.
6. 6. McIntosh TK, Saatman KE, Raghupathi R, et al. The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathology 1998;24:251–67. doi: 10.1046/j.1365- 2990.1998.00121.x
7. 7. Schmidt OI, Heyde CE, Ertel W, Stahel PF. Closed head injury-an inflammatory disease? Brain Res Rev 2005;483:388-99. doi:10.1016/j.brainresrev.2004.12.028
8. 8. Ghirnikar RS, Lee YL, Lawrence F. Inflammation in traumatic brain injury: Role of cytokines and chemokines. Neurochem Res 1998; 23: 329-40.

9. 9. Mocchetti I, Wrathall JR. Neurotrophic factors in central nervous system trauma. J Neurotrauma 1995;12:853-70. doi:10.1089/neu.1995.12.853
10. 10. Uhl MW, Biagas KV, Grundl PD, et al. Effects of neutropenia on edema, histology, and cerebral blood flow after traumatic brain injury in rats. J Neurotrauma 1994; 11: 303-15. doi:10.1089/neu.1994.11.303
11. 11. Miyasaki KT, Vilson M E, Genco RJ. Klinig of Actinobacillus actinomycetemcomitans by the Human Neutrophil MyeloperoxidaseHydrogen Peroxide Chloride System. Infect Immun 1986; 53:161-5.
12. 12. Nauseef WM. Insights into myeloperoxidase biosynthesis from its inherited deficiency. J Mol Med 1998;76:661-8.
13. 13. Biagas K V, Uhl M W, Schiding J K, Nemoto E M, Kochanek P M. Assessment of posttraumatic polymorphonuclear leukocyte accumulation in rat brain using tissue myeloperoxidase assay and vinblastine treatment. J Neurotrauma 1992; 9: 363-71.
14. 14. Loddick SA, Rothwel NJ. Neuroprotective effects of human recombinant IL-1 receptor antagonist in focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1996;16:932-940
15. 15. Dietrich WD, Alonso O, Halley M. Early microvascular and neuronal consequences to traumatic brain injury: a light and electron microscopic study in rats. J Neurotrauma 1994;11: 289-301.
16. 16. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87:2095-147.
17. 17. Woodroofe MN, Sarna GS, Wadhwa M, et al. Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production. J Neuroimmunology 1991;33:227-36. doi:10.1016/0165-5728(91)90110-S
18. 18. Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T. Inflammatory response in acute traumatic brain injury: a doubleedged sword. Curr Opin Crit Care 2002;8:101–5.
19. 19. Patel HC. Interleukin-1 in the brain mechanisms of action in acute neurodegeneration. Ann N Y Acad Sci. 2003;992:39-47. doi: 10.1111/j.1749-6632.2003.tb03136.x
20. 20. Shohami E, Gallily R, Mechoulam R, Bass R, Ben-Hur T. Cytokine production in the brain following closed head injury: dexanabinol HU-211 is a novel TNF- inhibitor and an effective neuroprotectant. J Neuroimmunol. 1997;72:169-77.
21. 21. Zaremba J, Losy J. Cytokines in clinical and experimental ischemic stroke. Neurol Neurochir 2004;38:57-62.
22. 22. Shohami E, Novikov M, Bass R, et al. Closed head injury triggers early production of TNF-α and IL-6 by brain tissue. J Cereb Blood Flow Metab 1994;14: 615-9.
23. 23. Kossmann T, Hans V, Imhof HG, et al. Intrathecal and serum interleukin-6 and the acute phase response in patients with severe traumatic brain injuries. Shock 1995;5: 311– 7.
24. 24. Morganti-Kossmann MC, Lenzlinger PM, Stahel P, et al. Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Mol Psychiatry 1997;2: 133–6.
25. 25. Utagawa A, Truettner JS, Dietrich WD, Bramlett HM. Systemic inflammation exacerbates behavioral and histopathologica consequences of ısolated traumatic brain injury in rats. Exp Neurol 2008; 211: 283–91. doi:10.1016/j.expneurol.2008.02.001