Chronic traumatic encephalopathy: the nature, mechanisms and stages of development

Authors

DOI:

https://doi.org/10.25305/unj.168890

Keywords:

traumatic brain injury, traumatic chronic encephalopathy, tau protein, neuroinflammation

Abstract

The survey provides data on the history of discovery and the epidemiology of chronic traumatic encephalopathy, which can occur after a single or repeated mild traumatic brain injury. Chronic traumatic encephalopathy has a nearly century-long history and was first identified in boxing veterans. Initially, signs of progressive neurological disease (punch-drunk), which occurred after repeated multiple traumatic brain injury in boxers, were described. Other sport activities alongside with box, associated with repeated mild brain injuries may cause dementia and neurodegenerative diseases. That led to the use of the term “chronic traumatic encephalopathy” (CTE). The features of the disease are defined, namely, that it occurs many years after the injury and develops in very small percentage of persons experienced a head injury, and clinically it resembles such neurodegenerative disorders as Parkinson’s and Alzheimer’s diseases. The paper deals with the pathogenesis associated with the accumulation of beta amyloid, tau protein, the development of neuro-inflammation and immune-associated reactions, including intracerebral local and systemic immune processes. The review indicates the role of genetic susceptibility, resistance to injury, gender, physiological stress, environmental exposure and age in the development of CTE.

The significance of immune responses and inflammation in the development of various forms of neurodegenerative diseases and CTE is widely recognized, but the mechanisms of the immunoprotective and immunodegenerative actions are still not well understood and require special experimental studies. The review notes different role of immune responses in the pathogenesis at certain stages of development of CTE.

The protective and immunopathological mechanisms of chronic traumatic encephalopathy are analyzed in detail; three main periods of its development have been identified, and new approaches to the study and treatment have been outlined.

Author Biographies

Eugene G. Pedachenko, Romodanov Neurosurgery Institute, Kyiv

Director

Nikolay I. Lisianyi, Romodanov Neurosurgery Institute, Kyiv

Department of Neuroimmunology

References

1. Gardner RC, Yaffe K. Epidemiology of mild traumatic brain injury and neurodegenerative disease. Mol Cell Neurosci. 2015 May;66(Pt B):75-80. [CrossRef] [PubMed] [PubMed Central]

2. McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, Lee HS, Wojtowicz SM, Hall G, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013 Jan;136(Pt 1):43-64. [CrossRef] [PubMed] [PubMed Central]

3. Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma. 2010 Aug;27(8):1529-40. [CrossRef] [PubMed]

4. Kiraly M, Kiraly SJ. Traumatic brain injury and delayed sequelae: a review - traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Scientific World Journal. 2007 Nov;7:1768-76. [CrossRef] [PubMed] [PubMed Central]

5. Emmerling MR, Morganti-Kossmann MC, Kossmann T, Stahel PF, Wat son MD, Evans LM, Mehta PD, Spiegel K, Kuo YM, Roher AE, Raby CA.. Traumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann N Y Acad Sci. 2000;903:118-22. [CrossRef] [PubMed]

6. Cernak I. Animal models of head trauma. NeuroRx. 2005 Jul;2(3):410-22. [CrossRef] [PubMed] [PubMed Central]

7. Martland HS. Punch drunk. J Am Med Assoc. 1928;91(15):1103-7. [CrossRef]

8. Roberts A. Brain damage in boxers: A study of prevalence of traumatic encephalopathy among ex-professional boxers. London: Pitman Medical Scientific Publishing Co.; 1969.

9. Tsolaki M, Fountoulakis K, Chantzi E, Kazis A. Risk factors for clinically diagnosed Alzheimer’s disease: a case-control study of a Greek population. Int Psychogeriatr. 1997 Sep;9(3):327-341. [CrossRef] [PubMed]

10. Weiner MW, Crane PK, Montine TJ, Bennett DA. Traumatic brain injury may not increase the risk of Alzheimer disease. Neurology. 2017 Oct;89(18):1923-1925. [CrossRef] [PubMed] [PubMed Central]

11. McKee AC, Stein TD, Kiernan PT, Alvarez VE. The neuropathology of chronic traumatic encephalopathy. Brain Pathol. 2015 May;25(3):350-64. [CrossRef] [PubMed] [PubMed Central]

12. O’Meara ES, Kukull WA, Sheppard L, Bowen JD, McCormick WC, Teri L, Pfanschmidt M, Thompson JD, Schellenberg GD, Larson EB. Head injury and risk of Alzheimer’s disease by apolipoprotein E genotype. Am J Epidemiol. 1997 Sep;146(5):373-84. [CrossRef] [PubMed]

13. Rasmusson DX, Brandt J, Martin DB, Folstein MF. Head injury as a risk factor in Alzheimer’s disease. Brain Inj. 1995 Apr;9(3):213-9. [CrossRef] [PubMed]

14. Castellani RJ, Perry G, Iverson GL. Chronic effects of mild neurotrauma: putting the cart before the horse? J Neuropathol Exp Neurol. 2015 Jun;74(6):493-9. [CrossRef] [PubMed] [PubMed Central]

15. McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010 Sep;69(9):918-29. [CrossRef] [PubMed] [PubMed Central]

16. Wang HK, Lee YC, Huang CY, Liliang PC, Lu K, Chen HJ, Li YC, Tsai KJ. Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis. Neuroscience. 2015 Aug 6;300:94-103. [CrossRef] [PubMed]

17. Schoch KM, Evans HN, Brelsfoard JM, Madathil SK, Takano J, Saido TC, Saatman KE. Calpastatin overexpression limits calpain-mediated proteolysis and behavioural deficits following traumatic brain injury. Exp Neurol. 2012;236(2):371-82. [CrossRef] [PubMed] [PubMed Central]

18. de Calignon A, Polydoro M, Suárez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron. 2012 Feb 23;73(4):685-97. [CrossRef] [PubMed] [PubMed Central]

19. McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 2009 Jul;68(7):709-35. [CrossRef] [PubMed] [PubMed Central]

20. Liu L, Drouet V, Wu JW, Witter MP, Small SA, Clelland C, Duff K. Trans-synaptic spread of tau pathology in vivo. PLoS One. 2012;7(2):e31302. [CrossRef] [PubMed] [PubMed Central]

21. Amadoro G, Ciotti MT, Costanzi M, Cestari V, Calissano P, Canu N. NMDA receptor mediates tau-induced neurotoxicity by calpain and ERK/MAPK activation. Proc Natl Acad Sci U S A. 2006 Feb;103(8):2892-7. [CrossRef] [PubMed] [PubMed Central]

22. Khlistunova I, Biernat J, Wang Y, Pickhardt M, von Bergen M, Gazova Z, Mandelkow E, Mandelkow EM. Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem. 2006 Jan 13;281(2):1205-14. [CrossRef] [PubMed]

23. Tran HT, Sanchez L, Esparza TJ, Brody DL. Distinct temporal and anatomical distributions of amyloid-β and tau abnormalities following controlled cortical impact in transgenic mice. PLoS One. 2011;6(9):e25475. [CrossRef] [PubMed] [PubMed Central]

24. Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain. 2003 Mar;126(Pt 3):515-30. [CrossRef] [PubMed]

25. Saing T, Dick M, Nelson PT, Kim RC, Cribbs DH, Head E. Frontal cortex neuropathology in dementia pugilistica. J Neurotrauma. 2012 Apr 10;29(6):1054-70. [CrossRef] [PubMed] [PubMed Central]

26. 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]

27. Giunta B, Obregon D, Velisetty R, Sanberg PR, Borlongan CV, Tan J. The immunology of traumatic brain injury: a prime target for Alzheimer’s disease prevention. J Neuroinflammation. 2012 Aug;9:185. [CrossRef] [PubMed] [PubMed Central]

28. Walsh JG, Muruve DA, Power C. Inflammasomes in the CNS. Nat Rev Neurosci. 2014 Feb;15(2):84-97. [CrossRef] [PubMed]

29. Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 2015 Mar;72(3):355-62. [CrossRef] [PubMed] [PubMed Central]

30. 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]

31. Gadani SP, Walsh JT, Lukens JR, Kipnis J. Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron. 2015 Jul;87(1):47-62. [CrossRef] [PubMed] [PubMed Central]

32. Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013 Jan;136(Pt 1):28-42. [CrossRef] [PubMed] [PubMed Central]

33. Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, Gentleman S, Heckemann RA, Gunanayagam K, Gelosa G, Sharp DJ. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol. 2011 Sep;70(3):374-83. [CrossRef] [PubMed]

34. Loane DJ, Pocivavsek A, Moussa CE, Thompson R, Matsuoka Y, Faden AI, Rebeck GW, Burns MP. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med. 2009 Apr;15(4):377-9. [CrossRef] [PubMed] [PubMed Central]

35. Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer’s disease. Nat Immunol. 2015 Mar;16(3):229-36. [CrossRef] [PubMed]

36. Washington PM, Villapol S, Burns MP. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy? Exp Neurol. 2016 Jan;275 Pt 3:381-388. [CrossRef] [PubMed] [PubMed Central]

37. Washington PM, Morffy N, Parsadanian M, Zapple DN, Burns MP. Experimental traumatic brain injury induces rapid aggregation and oligomerization of amyloid-beta in an Alzheimer’s disease mouse model. J Neurotrauma. 2014 Jan 1;31(1):125-34. [CrossRef] [PubMed] [PubMed Central]

38. Romas VS, Dekhtyar VD. Nekotoryye prichiny dekompensatsii i klinicheskiye struktury otdalennykh issledovaniy posledstviy cherepno-mozgovoy travmy. Respublikanskiy mezhvedomstvennyy sbornik «Nevrologiya i psikhiatriya» (Kiev: Zdorov’ya). 1979;7:28-30. Russian.

39. Filatova AD, Mikhaylenko YK. Osnovnyye faktory, vyzyvayushchiye dekompensatsiyu v otdalennom periode zakrytoy cherepno-mozgovoy travmy. Respublikanskiy mezhvedomstvennyy sbornik «Nevrologiya i psikhiatriya» (Kiev: Zdorov’ya). 1979;7: 18-28. Russian.

40. Vasilyeva IG, Vasilyev AN, Kostyuk MR, Kurako YuL, Lisyany NI, Nosov AT, Omelchenko VV, Pedachenko GA, Pedachenko EG, Rudenko VA, Cherchenko AP, Chopik NG. Current ideas about the pathogenesis of closed traumatic brain injury. Kiev: Zadruga; 1996. Russian.

41. Ushakova GO, Babets YV., Kirichenko SV. Molecular mechanisms of the development of encephalopathy. Dnipro: DNU; 2017. 203 p. Ukrainian.

42. Shkolnyk V, Fesenko G, Golyk V, Pogorielova S, Pashkovskyi V, Huk A. Remote cognitive impairments after traumatic brain injury as a disability cause. Ukrainian Neurosurgical Journal. 2015;(2):5-10. Ukrainian. [CrossRef]

43. Shevaga VM, Kuhlenko OY, Kuhlenko RV. Clinical and instrumental diagnostics of cognitive deficit in an acute period of traumatic brain injury of mild and moderate severity Ukrainian neurological journal. 2009;(3):51-4.

44. Mironenko TV, Smirnova MP, Kazartseva SN. About the question of consecquences of mild craniocerebral trauma. Zagalna patologia i patologichna fisiologia. 2007;(6):40-7. Russian.

45. Lichko VS, Lichko VS, Petrenko VY, Petrenko VY, Malakhov VO, Belevtsova EN, Zubkov AV. Chronic traumatic encephalopathy (Мartland’s syndrome). Journal of Clinical and Experimental Medical Research. 2016;4(1):146-152. Ukrainian. Available from: http://essuir.sumdu.edu.ua/handle/123456789/44771

46. Lisyanyy MI, Nosov AT, Kadzhaya MV. The Pathogenegical Basis Of The Progredient Course Of Mild Repeated Mild Craniocerebral Injury. Intehratyvna Antropolohiya. 2010;(1):57-61. Ukrainian.

47. Gorbunov VI. Second mild cranial cerebral trauma within the intermediate period of traumatic disease of the brain (clinical and immunological investigation). Russian Journal of Neurosurgery. 2002;(3):21-5. Russian. Available from: https://elibrary.ru/item.asp?id=21788364

48. Pedachenko EG, Sutkovoĭ DA, Lisianyĭ AN, Rudenko VA, Guk AP, Markina EA, Glushchenko NV, Fedosenko TN. [Free-radical and neuroimmune processes in primary and repeated craniocerebral trauma (in an experiment)]. Zh Vopr Neirokhir Im N N Burdenko. 1998 Oct-Dec;(4):24-7. Russian. [PubMed]

49. Lekomtseva YV. Serum tau protein level in patients with long-term consequences of the mild brain traumatic injury. Ukrainian Neurological Journal. 2019 Mar 29;(1):17–20. Ukrainian. [CrossRef]

50. Polishchuk ME, Muravskiy AV. Traumatic brain injuries in boxers. Ukrainian neurological journal. 2008;(4):57-65. Ukrainian.

51. Muravskiy AV, Dekhtyaryov YuP, Kolosovsky SO. Features of clinical and hemodynamic disorders in boxers who have a history of recurrent mild traumatic brain injuries. Pathology. 2010;7(2):47-9. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/pathology_2010_7_2_13

52. Muravskyi AV. Features of neurotropic autoantibodies content in boxers with mild brain injuries. Coliection of scientific works of staff member of P. L. Shupyk NMAPE. 2013;22(1):169-76. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Znpsnmapo_2013_22(1)__28

53. Salii ZV, Shkrobot SI. Clinical and laboratory correlation in patients with consequences of traumatic brain injury. Ukrainian neurological journal. 2015;(4):68-72. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/UNJ_2015_4_12

Published

2019-09-28

How to Cite

Pedachenko, E. G., & Lisianyi, N. I. (2019). Chronic traumatic encephalopathy: the nature, mechanisms and stages of development. Ukrainian Neurosurgical Journal, 25(3), 5–11. https://doi.org/10.25305/unj.168890

Issue

Section

Review articles