The dual role of the immune system in the pathogenesis of traumatic brain injury
DOI:
https://doi.org/10.25305/unj.155107Keywords:
traumatic brain injury, immune system, autoimmune reactions, inflammation, regenerationAbstract
Studies of the recent 10–15 years in the field of immunology have been obtained new data on the immune system structure, the functions of cells of innate and acquired immunity, the mechanisms of development of both immunopathological, damaging, and protective, stimulating tissue repair effect of immune reactions in the body as a whole including with TBI. The review examines the mechanism of development of the immune response to neurotrauma, which includes: 1) the initial activation of cells of innate immunity, namely microglia in the brain, 2) microglia synthesis of cytokines and attraction of peripheral immune cells into the brain parenchyma, 3) development of systemic specific immune and inflammatory reactions in the body. The article shows that immune reactions develop over time after TBI and may have a dual effect, namely, beneficial brain cleansing of dead cells and stimulating neuronal repair, and an immunopathological effect on the course of injury, which can lead to early or delayed neurodegeneration after TBI. Based on this duality of the influence of immune reactions on the course of neurotrauma, the review points to the need to further study of these immune processes during TBI, and to develop methods for targeted immunomodulation, which can significantly improve the results of treatment of acute TBI and its long-term effects.
References
1. Romodanov AP, Lisianyi NI. Traumatic brain injury and immunological reactivity. Kiev: Zdorov'ya; 1991. Russian.
2. Das M, Mohapatra S, Mohapatra SS. New perspectives on central and peripheral immune responses to acute traumatic brain injury. J Neuroinflammation. 2012 Oct 12;9:236. [CrossRef] [PubMed] [PubMed Central]
3. Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotectionin traumatic brain injury. JAMA Neurol. 2015 Mar;72(3):355-62. [CrossRef] [PubMed] [PubMed Central]
4. Chiu CC, Liao YE, Yang LY, Wang JY, Tweedie D, Karnati HK, Greig NH, Wang JY. Neuroinflammation in animal models of traumatic brain injury. J Neurosci Methods. 2016 Oct;272:38-49. [CrossRef] [PubMed] [PubMed Central]
5. Lisianyĭ II, Cheren'ko TM, Komissarenko SV, Berezhnoĭ GA, Tukhtiev NKh, Arustamian RS. [The determination of neurospecific proteins in the blood of patients with closed craniocerebral trauma and their diagnostic significance]. Zh Nevrol Psikhiatr Im S S Korsakova. 1993;93(2):50-3. Russian. [PubMed]
6. Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B, Fernandes J, Gogichaisvili T, Golden N, Hartzenberg B. Final results of MRC CRASH, a randomised placebocontrolledtrial of intravenous corticosteroid in adults with head injury-outcomesat 6 months. Lancet. 2005 Jun;365(9475):1957-1959. [CrossRef] [PubMed]
7. Roberts DJ, Jenne CN, Léger C, Kramer AH, Gallagher CN, Todd S, Parney IF, Doig CJ, Yong VW, Kubes P, Zygun DA. A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans. J Neurotrauma. 2013 Oct 15;30(20):1717-26. [CrossRef] [PubMed]
8. Pedachenko EG, editor. [Modern ideas about the pathogenesis of closed traumatic brain injury]. Kyiv: Zadruga; 1996. 282 p. Russian.
9. Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Exp Neurol. 2016 Jan; 275(Pt 3):367-380. [CrossRef] [PubMed] [PubMed Central]
10. McIntosh TK, Smith DH, Meaney DF, Kotapka MJ, Gennarelli TA, Graham DI. Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Invest. 1996 Feb;74(2):315-42. [PubMed]
11. Cernak I. Animal models of head trauma. NeuroRx. 2005 Jul;2(3):410-22. [CrossRef] [PubMed] [PubMed Central]
12. DeKosky ST, Kochanek PM, Clark RS, Ciallella JR, Dixon CE. Secondary injury after head trauma: subacute and long-term mechanisms. Semin Clin Neuropsychiatry. 1998 Jul;3(3):176-185. [PubMed]
13. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006 Jan;147 Suppl 1:S232-40. [CrossRef] [PubMed] [PubMed Central]
14. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4-9. [CrossRef] [PubMed]
15. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta. 2012 May;1822(5):675-84. [CrossRef] [PubMed] [PubMed Central]
16. Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008 Aug;7(8):728-41. [CrossRef] [PubMed]
17. Zhang YB, Li SX, Chen XP, Yang L, Zhang YG, Liu R, Tao LY. Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull. 2008 Jun;24(3):143-149. [CrossRef] [PubMed] [PubMed Central]
18. Zozulya YuP, Lisianyi MI. Clinical significance of neuroimmune disorders in neurosurgical pathology. Journal of the Academy of Medical Sciences of Ukraine. 1996;(4):592-610. Ukrainian.
19. Biloshytsky VV. The principles of experimental traumatic brain injury modelling. Ukrainian Neurosurgical Journal. 2008;(4):9-16. [CrossRef]
20. Lisyanyy NI, Cherenko TM. Kletochnyy immunnyy otvet na neyrospetsificheskiye belki u bol'nykh s zakrytoy cherepno-mozgoy travmoy. Immunologiya i Allergologiya: Respublikanskiy Sbornik. 1986;22:93-95. Russian.
21. Smrcka M, Mrlian A, Karlsson-Valik J, Klabusay M. The effect of head injury upon the immune system. Bratisl Lek Listy. 2007;108(3):144-8. [PubMed]
22. Utagawa A, Truettner JS, Dietrich WD, Bramlett HM. Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats. Exp Neurol. 2008 May;211(1):283-91. [CrossRef] [PubMed] [PubMed Central]
23. Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed). 2009 Jan;14:3795-813. [PubMed]
24. Keel M, Trentz O. Pathophysiology of polytrauma. Injury. 2005 Jun;36(6):691-709. [CrossRef] [PubMed]
25. Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013 Mar;4:18. [CrossRef] [PubMed] [PubMed Central]
26. Harry GJ. Microglia during development and aging. Pharmacol Ther. 2013 Sep;139(3):313-26. [CrossRef] [PubMed] [PubMed Central]
27. Cernak I. Animal models of head trauma. NeuroRx. 2005;2:410–422. [CrossRef] [PubMed] [PubMed Central]
28. Smrcka M, Mrlian A, Karlsson-Valik J, Klabusay M. The effect of head injury upon the immune system. Bratisl Lek Listy. 2007;108(3):144-8. [PubMed]
29. Smith RM, Giannoudis PV. Trauma and the immune response. J R Soc Med. 1998 Aug; 91(8):417-420. [PubMed] [PubMed Central]
30. DiPiro JT, Howdieshell TR, Goddard JK, Callaway DB, Hamilton RG, Mansberger AR Jr. Association of interleukin-4 plasma levels with traumatic injury and clinical course. Arch Surg. 1995 Nov;130(11):1159-62; discussion 1162-3. [CrossRef] [PubMed]
31. Marcu AC, Paccione KE, Barbee RW, Diegelmann RF, Ivatury RR, Ward KR, Loria RM. Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage shock model. J Trauma. 2007 Sep;63(3):662-9. [CrossRef] [PubMed]
32. Zamora R, Vodovotz Y, Billiar TR. Inducible nitric oxide synthase and inflammatory diseases. Mol Med. 2000 May;6(5):347-73. [PubMed] [PubMed Central]
33. Hierholzer C, Harbrecht B, Menezes JM, Kane J, MacMicking J, Nathan CF, Peitzman AB, Billiar TR, Tweardy DJ. Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J Exp Med. 1998 Mar;187(6):917-28. [CrossRef] [PubMed] [PubMed Central]
34. Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev. 2003 Oct;14(5):409-26. [CrossRef] [PubMed]
35. Das M, Leonardo CC, Rangooni S, Pennypacker KR, Mohapatra S, Mohapatra SS. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats. J Neuroinflammation. 2011 Oct;8:148. [CrossRef] [PubMed] [PubMed Central]
36. Kappe C, Tracy LM, Patrone C, Iverfeldt K, Sjöholm Å. GLP-1 secretion by microglial cells and decreased CNS expression in obesity. J Neuroinflammation. 2012 Dec;9:276. [CrossRef] [PubMed] [PubMed Central]
37. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013 Mar;13(3):159-75. [CrossRef] [PubMed]
38. Soares HD, Hicks RR, Smith D, McIntosh TK. Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. J Neurosci. 1995 Dec;15(12):8223-33. [PubMed]
39. Carlos TM, Clark RS, Franicola-Higgins D, Schiding JK, Kochanek PM. Expression of endothelial adhesion molecules and recruitment of neutrophils after traumatic brain injury in rats. J Leukoc Biol. 1997 Mar;61(3):279-85. [PubMed]
40. Szmydynger-Chodobska J, Strazielle N, Gandy JR, Keefe TH, Zink BJ, Ghersi-Egea JF, Chodobski A. Posttraumatic invasion of monocytes across the blood-cerebrospinal fluid barrier. J Cereb Blood Flow Metab. 2012;32(1):93-104. [CrossRef] [PubMed] [PubMed Central]
41. Schwarzmaier SM, Plesnila N. Contributions of the immune system to the pathophysiology of traumatic brain injury – evidence by intravital microscopy. Front Cell Neurosci. 2014;8:358. [CrossRef] [PubMed] [PubMed Central]
42. Russo MV, McGavern DB. Immune surveillance of the CNS following infection and injury. Trends Immunol. 2015; 36(10):637-50. [CrossRef] [PubMed] [PubMed Central]
43. Villapol S, Byrnes KR, Symes AJ. Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte-vasculature interaction and astrogliosis in the pericontusional region after traumatic brain injury. Front Neurol. 2014;5:82. [CrossRef] [PubMed] [PubMed Central]
44. Ren Z, Iliff JJ, Yang L, Yang J, Chen X, Chen MJ, Giese RN, Wang B, Shi X, Nedergaard M. “Hit & Run” model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation. J Cereb Blood Flow Metab. 2013;33(6):834-45. [CrossRef] [PubMed] [PubMed Central]
45. Lisianyi NI, Pedachenko EG, Kadzhaya NV. Features of the development of autoimmune reactions with repeated TBI. Immunology and Allergy. 2006;(3): 50-53. Russian.
46. Czigner A, Mihály A, Farkas O, Büki A, Krisztin-Péva B, Dobó E, Barzó P. Kinetics of the cellular immune response following closed head injury. Acta Neurochir (Wien). 2007;149(3):281-9. [CrossRef] [PubMed]
47. Clausen F, Lorant T, Lewén A, Hillered L. T lymphocyte trafficking: a novel target for neuroprotection in traumatic brain injury. J Neurotrauma. 2007 Aug;24(8):1295-307. [CrossRef] [PubMed]
48. Weckbach S, Neher M, Losacco JT, Bolden AL, Kulik L, Flierl MA, Bell SE, Holers VM, Stahel PF. Challenging the role of adaptive immunity in neurotrauma: Rag1(-/-) mice lacking mature B and T cells do not show neuroprotection after closed head injury. J Neurotrauma. 2012 Apr;29(6):1233-42. [CrossRef] [PubMed] [PubMed Central]
49. Mencl S, Hennig N, Hopp S, Schuhmann MK, Albert-Weissenberger C, Siren AL, Kleinschnitz C. FTY720 does not protect from traumatic brain injury in mice despite reducing posttraumatic inflammation. J Neuroimmunol. 2014 Sep;274(1-2):125-31. [CrossRef] [PubMed]
50. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med. 1999 Jan;5(1):49-55. [CrossRef] [PubMed]
51. Ellwardt E, Walsh JT, Kipnis J, Zipp F. Understanding the role of T cells in CNS homeostasis. Trends Immunol. 2016; 37(2):154-65. [CrossRef] [PubMed]
52. Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens JR, Gadani S, Hechler D, Gölz G, Rosenberger K, Kammertöns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti TD, Nitsch R, Zipp F, Kipnis J. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest. 2015 Feb;125(2):699-714. [CrossRef]
53. Griffin GD. The injured brain: TBI, mTBI, the immune system, and infection: connecting the dots. Mil Med. 2011 Apr;176(4):364-368. [PubMed]
54. Wolach B, Sazbon L, Gavrieli R, Broda A, Schlesinger M. Early immunological defects in comatose patients after acute brain injury. J Neurosurg. 2001 May;94(5):706-11. [CrossRef] [PubMed]
55. Dziedzic T, Slowik A, Szczudlik A. Nosocomial infections and immunity: lesson from brain-injured patients. Crit Care. 2004;8(4):266-70. [CrossRef] [PubMed] [PubMed Central]
56. Lisianyĭ NI, Prikhodchenko IA, Rudenko VA. [B-immunity system indices of patients with closed craniocerebral injury]. Fiziol Zh. 1984 Jul-Aug;30(4):463-7. Russian. [PubMed]
57. Lisyany NI, Cherenko TM, Terletskaya YT. Dynamics of Revealing Antibodies to Main Myelin Protein in Patients with Closed Head Injury. Vrachebnoe Delo. 1987;(10):101-104. Russian.
58. Lisianyi MI, Nosov AT, Kadjaya MV. Pathogenetic bases of the recurrent craniocerebral trauma. Integrative Anthropology. 2010;1(15):57-61. Ukrainian.
59. Muravskyi AV, Lisianyi MI, Belska LM. Effect of mild craniocerebral injury of boxers on the development of autoimmune reactions and their clinical and prognostic significance. Hospital Surgery. 2012;(4):37-42. Ukrainian. http://nbuv.gov.ua/UJRN/shpkhir_2012_4_10
60. Becher B, Prat A, Antel JP. Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia. 2000 Feb;29(4):293-304. [CrossRef] [PubMed]
61. Mirzayan MJ, Probst C, Krettek C, Samii M, Pape HC, van Griensven M, Samii A. Systemic effects of isolated brain injury: an experimental animal study. Neurol Res. 2008;30(5):457-60. [CrossRef]
62. Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, Hong NH, Kim JH, Ban JJ, Park HK, Kim SU, Park CG, Lee SK, Kim M, Roh JK. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain. 2008 Mar;131(Pt 3):616-29. [CrossRef] [PubMed]
63. Ajmo CT Jr, Collier LA, Leonardo CC, Hall AA, Green SM, Womble TA, Cuevas J, Willing AE, Pennypacker KR. Blockade of adrenoreceptors inhibits the splenic response to stroke. Exp Neurol. 2009 Jul;218(1):47-55. [CrossRef] [PubMed] [PubMed Central]
64. Das M, Leonardo CC, Rangooni S, Pennypacker K, Mohapatra S, Mohapatra SS. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats. J Neuroinflammation. 2011 Oct;8:148. [CrossRef] [PubMed] [PubMed Central]
65. Radzievsky AA. Correction of the cellular and subpopulation composition of the lymphoid organs of rats after severe traumatic brain injury with the help of lymphoid preparations. In: Proceedings of the Republican Conference «Immunostimulation Mechanisms». Kiev, Ukraine. 1985. P.191-196. Russian.
66. Guan J, Jin D, Jin L. Apoptosis in multiple organs of rats in early stage of polytrauma combined with shock. Zhonghua Yi Xue Za Zhi. 1998 Oct;78(10):741-5. [PubMed]
67. Xiong Y, Mahmood A, Meng Y, Zhang Y, Zhang ZG, Morris DC, Chopp M. Treatment of traumatic brain injury with thymosin β4 in rats. J Neurosurg. 2011 Jan; 114(1):102-115. [CrossRef] [PubMed] [PubMed Central]
68. Campbell SJ, Zahid I, Losey P, Law S, Jiang Y, Bilgen M, van Rooijen N, Morsali D, Davis AE, Anthony DC. Liver Kupffer cells control the magnitude of the inflammatory response in the injured brain and spinal cord. Neuropharmacology. 2008;55(5):780-7. [CrossRef] [PubMed]
69. Campbell SJ, Perry VH, Pitossi FJ, Butchart AG, Chertoff M, Waters S, Dempster R, Anthony DC. Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver. Am J Pathol. 2005 May;166(5):1487-97. [CrossRef] [PubMed] [PubMed Central]
70. Moinard C, Gupta S, Besson V, Morio B, Marchand-Leroux C, Chaumeil JC, Cynober L, Charrueau C. Evidence for impairment of hepatic energy homeostasis in head-injured rat. J Neurotrauma. 2008;25(2):124-9. [CrossRef] [PubMed]
71. Kamm K, Vanderkolk W, Lawrence C, Jonker M, Davis AT. The effect of traumatic brain injury upon the concentration and expression of interleukin-1beta and interleukin-10 in the rat. J Trauma. 2006 Jan;60(1):152-7. [CrossRef] [PubMed]
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