Sustained Tau Phosphorylation and Microglial Activation Following Repetitive Traumatic Brain Injury

Authors

  • Andre Marolop Pangihutan Siahaan Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia http://orcid.org/0000-0003-1107-055X
  • Rr Suzy Indharty Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Jessy Chrestella Department of Anatomic Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Wismaji Sadewo Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Steven Tandean Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Siti Syarifah Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.5471

Keywords:

Activated microglia, Repetitive traumatic brain injury, Phosphorylated tau

Abstract

BACKGROUND: Repetitive traumatic brain injury (TBI), even without acute sequela, can induce a delayed neurodegenerative with overexpression of phosphorylated tau (p-tau) as hallmark, caused by chronic inflammation mediated in part by microglial activation.

AIM: The aim of this study was to examine the dynamics of p-tau accumulation and microglial activation following repetitive TBI.

MATERIALS AND METHODS: Thirty Sprague–Dawley rats were randomized into a sham control group and two treatment groups receiving three successive closed-skull impacts (TBI model) from a 40-g mass dropped from a 1-m height on alternating days (days 0, 1, 3, and 7). The first treatment group was sacrificed on the last day of trauma and the second treatment group after 7 days of no trauma. The expression level of p-tau was evaluated by AT-8 antibody immunostaining and microglial activation by anti-CD-68 immunostaining.

RESULTS: Immunoexpression of AT-8 was significantly elevated 7 days after TBI compared to the last day of trauma and compared to the sham control group, while CD-68 expression was significantly higher than sham controls on the last day of trauma and remained elevated for 7 days without trauma.

CONCLUSION: The study showed that brain trauma can induce p-tau overexpression and microglial activation that is sustained during the non-trauma period.

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Author Biography

Andre Marolop Pangihutan Siahaan, Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

Department of Neurosurgery

References

Wang HK, Lin SH, Sung PS, Wu MH, Hung KW, Wang LC, et al. Population based study on patients with traumatic brain injury suggests increased risk of dementia. J Neurol Neurosurg Psychiatry. 2012;83(11):1080-5. https://doi.org/10.1136/jnnp-2012-302633 PMid:22842203

Barnes DE, Kaup A, Kirby KA, Byers AL, Diaz-Arrastia R, Yaffe K. Traumatic brain injury and risk of dementia in older veterans. Neurology. 2014;83(4):312-9. https://doi.org/10.1212/wnl.0000000000000616 PMid:24966406

Hawkins BE, Krishnamurthy S, Castillo-Carranza DL, Sengupta U, Prough DS, Jackson GR, et al. Rapid accumulation of endogenous tau oligomers in a rat model of traumatic brain injury: Possible link between traumatic brain injury and sporadic tauopathies. J Biol Chem. 2013;288(23):17042-50. https://doi.org/10.1074/jbc.m113.472746 PMid:23632019

Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-β pathology: A link to Alzheimer’s disease? Nat Rev Neurosci. 2010;11(5):361-70. https://doi.org/10.1038/nrn2808 PMid:20216546

McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol. 2017;131(1):75-86. https://doi.org/10.1007/s00401-015-1515-z PMid:26667418

Montenigro PH, Bernick C, Cantu RC. Clinical Features of Repetitive Traumatic Brain Injury and Chronic Traumatic Encephalopathy. Brain Pathol. 2015;25(3):304-17. https://doi.org/10.1111/bpa.12250 PMid:25904046

Omalu B. Chronic traumatic encephalopathy. Prog Neurol Surg. 2014;28:38-49. PMid:24923391

Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron. 2011;70(3):410-26. https://doi.org/10.1016/j.neuron.2011.04.009 PMid:21555069

Lucke-Wold BP, Turner RC, Logsdon AF, Bailes JE, Huber JD, Rosen CL. Linking traumatic brain injury to chronic traumatic encephalopathy: Identification of potential mechanisms leading to neurofibrillary tangle development. J Neurotrauma. 2014;31(13):1129-38. https://doi.org/10.1089/neu.2013.3303 PMid:24499307

Loane DJ, Kumar A. Microglia in the TBI brain: The good, the bad, and the dysregulated. Exp Neurol. 2016;275 Pt 3(0 3):316-27. https://doi.org/10.1016/j.expneurol.2015.08.018 PMid:26342753

Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI. Progressive neurodegeneration after experimental brain trauma: Association with chronic microglial activation. J Neuropathol Exp Neurol. 2014;73(1):14-29. https://doi.org/10.1097/nen.0000000000000021 PMid:24335533

De Calignon A, Polydoro M, Suárez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, et al. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron. 2012;73(4):685-97. https://doi.org/10.1016/j.neuron.2011.11.033 PMid:22365544

Xu L, Nguyen JV, Lehar M, Menon A, Rha E, Arena J, et al. Repetitive mild traumatic brain injury with impact acceleration in the mouse: Multifocal axonopathy, neuroinflammation, and neurodegeneration in the visual system. Exp Neurol. 2016;275:436-49. https://doi.org/10.1016/j.expneurol.2014.11.004 PMid:25450468

McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(1):43-64. PMid:23208308

Cherry JD, Tripodis Y, Alvarez VE, Huber B, Kiernan PT, Daneshvar DH, et al. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun. 2016;4:112. https://doi.org/10.1186/s40478-016-0382-8 PMid:27793189

Collins-Praino LE, Corrigan F. Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury? Brain Behav Immun. 2017;60:369-82. https://doi.org/10.1016/j.bbi.2016.09.027 PMid:27686843

Yoshiyama Y, Higuchi M, Zhang B, Huang S-M, Iwata N, Saido TC, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53(3):337-51. https://doi.org/10.1016/j.neuron.2007.01.010 PMid:17270732

Maphis N, Xu G, Kokiko-Cochran ON, Jiang S, Cardona A, Ransohoff RM, et al. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain. 2015;138(6):1738-55. https://doi.org/10.1093/brain/awv081 PMid:25833819

Simon DW, McGeachy MJ, Bayır H, Clark RSB, Loane DJ, Kochanek PM. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat Rev Neurol. 2017;13(3):171-91. https://doi.org/10.1038/nrneurol.2017.13 PMid:28186177

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;136(1):28-42. https://doi.org/10.1093/brain/aws322 PMid:23365092

Shitaka Y, Tran HT, Bennett RE, Sanchez L, Levy MA, Dikranian K, et al. Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J Neuropathol Exp Neurol. 2011;70(7):551-67. https://doi.org/10.1097/nen.0b013e31821f891f PMid:21666502

Blennow K, Brody DL, Kochanek PM, Levin H, McKee A, Ribbers GM, et al. Traumatic brain injuries. Nat Rev Dis Primers. 2016;2:16084. https://doi.org/10.1038/nrdp.2016.84 PMid:27853132

Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982;216(4542):136-44. https://doi.org/10.1126/science.6801762 PMid:6801762

Kriegel J, Papadopoulos Z, McKee AC. Chronic traumatic encephalopathy: Is latency in symptom onset explained by tau propagation? Cold Spring Harb Perspect Med. 2018;8(2):a024059. https://doi.org/10.1101/cshperspect.a024059 PMid:28096246

Van der Jeugd A, Hochgräfe K, Ahmed T, Decker JM, Sydow A, Hofmann A, et al. Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human tau. Acta Neuropathol. 2012;123(6):787-805. https://doi.org/10.1007/s00401-012-0987-3 PMid:22532069

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Published

2020-10-26

How to Cite

1.
Siahaan AMP, Indharty RS, Chrestella J, Sadewo W, Tandean S, Syarifah S. Sustained Tau Phosphorylation and Microglial Activation Following Repetitive Traumatic Brain Injury. Open Access Maced J Med Sci [Internet]. 2020 Oct. 26 [cited 2024 Mar. 28];8(A):837-40. Available from: https://oamjms.eu/index.php/mjms/article/view/5471

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Pathophysiology

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