CC BY-NC-ND 4.0 · Asian J Neurosurg 2020; 15(01): 10-15
DOI: 10.4103/ajns.AJNS_231_19
Review Article

Combined therapy potential of apocynin and tert-butylhydroquinone as a therapeutic agent to prevent secondary progression to traumatic brain injury

Rovie Parastan
Department of Medicine, Faculty of Medicine, Udayana University, Bali
,
Michael Christopher
Department of Medicine, Faculty of Medicine, Udayana University, Bali
,
Yesyurun Torrys
Department of Medicine, Faculty of Medicine, Udayana University, Bali
,
Tjokorda Mahadewa
1   Department of Neurosurgery, Faculty of Medicine, Udayana University, Bali
› Author Affiliations

Traumatic brain injury is caused by physical collision (primary injury). It changes the brain's biochemistry and disturbs the normal brain function such as memory loss and consciousness disturbance (secondary injury). The severity can be measured with the Glasgow Coma Scale. The secondary injury will cause oxidative stress that leads to the nervous cells death, so treatment is needed before it gets worse. Primary injury results in excess of reactive oxidative stress (ROS) which is known from NADPH oxidase 2 (Nox2). Excessive ROS is deadly to the nerve cells. Excessive ROS will activate nuclear factor erythroid 2-like 2 (Nrf2). Nrf2 will bind to antioxidant response elements, to protect multi organs against ROS, including this brain injury. However, this does not last long, so it requires handling excess ROS. Apocynin can inhibit the activation of Nox2, and reduce the neuron injuries in the hippocampus. It also protects the tissues from oxidative stress. While Nrf2 can be activated by tert-butylhydroquinone, to protect cells. The combination may reduce the secondary brain injury, improve the neurologic recovery, cognitive function, and reduce the secondary cortical lesion.

Financial support and sponsorship

Nil.




Publication History

Received: 19 July 2019

Accepted: 23 January 2020

Article published online:
16 August 2022

© 2020. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol 2015;72:355-62.
  • 2 Kabadi SV, Faden AI. Neuroprotective strategies for traumatic brain injury: Improving clinical translation. Int J Mol Sci 2014;15:1216-36.
  • 3 Faul M, Coronado V. Epidemiology of traumatic brain injury. In: Handbook of Clinical Neurology. Edinburg, London: Elsevier; 2015. p. 3-13.
  • 4 Maier D, Njoku I Jr., Schmutzhard E, Dharsee J, Doppler M, Härtl R, et al. Traumatic brain injury in a rural and an urban Tanzanian hospital – A comparative, retrospective analysis based on computed tomography. World Neurosurg 2014;81:478-82.
  • 5 Greve MW, Zink BJ. Pathophysiology of traumatic brain injury. Mt Sinai J Med 2009;76:97-104.
  • 6 Hinson HE, Rowell S, Schreiber M. Clinical evidence of inflammation driving secondary brain injury: A systematic review. J Trauma Acute Care Surg 2015;78:184-91.
  • 7 Kumar A, Loane DJ. Neuroinflammation after Traumatic Brain Injury: Opportunities for Theraupeutic Interventon. Edinburg, London: Elsevier; 2012. p. 1191-201.
  • 8 Hartings JA, Strong AJ, Fabricius M, Manning A, Bhatia R, Dreier JP, et al. Spreading depolarizations and late secondary insults after traumatic brain injury. J Neurotrauma 2009;26:1857-66.
  • 9 Pekic S, Popovic V. Alternative causes of hypopituitarism: Traumatic brain injury, cranial irradiation, and infections. In: Handbook of Clinical Neurology. Edinburg, London: Elsevier; 2014. p. 271-90.
  • 10 Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma HF, et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 2015;157:1683-96.
  • 11 Xiong Y, Mahmood A, Chopp M. Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs 2009;14:67-84.
  • 12 Choi BY, Jang BG, Kim JH, Lee BE, Sohn M, Song HK, et al. Prevention of traumatic brain injury-induced neuronal death by inhibition of NADPH oxidase activation. Brain Res 2012;1481:49-58.
  • 13 Lu XY, Wang HD, Xu JG, Ding K, Li T. Pretreatment with tert-butylhydroquinone attenuates cerebral oxidative stress in mice after traumatic brain injury. J Surg Res 2014;188:206-12.
  • 14 Jin W, Kong J, Wang H, Wu J, Lu T, Jiang J, et al. Protective effect of tert-butylhydroquinone on cerebral inflammatory response following traumatic brain injury in mice. Injury 2011;42:714-8.
  • 15 Chandran R, Kim T, Mehta SL, Udho E, Chanana V, Cengiz P, et al. A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury. J Cereb Blood Flow Metab 2018;38:1818-27.
  • 16 Thurman DJ. The epidemiology of traumatic brain injury in children and youths: A review of research since 1990. J Child Neurol 2016;31:20-7.
  • 17 Henry LC, Burkhart SO, Elbin RJ, Agarwal V, Kontos AP. Traumatic axonal injury and persistent emotional lability in an adolescent following moderate traumatic brain injury: A case study. J Clin Exp Neuropsychol 2015;37:439-54.
  • 18 Lozano D, Gonzales-Portillo GS, Acosta S, de la Pena I, Tajiri N, Kaneko Y, et al. Neuroinflammatory responses to traumatic brain injury: Etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr Dis Treat 2015;11:97-106.
  • 19 Angeloni C, Prata C, Dalla Sega FV, Piperno R, Hrelia S. Traumatic brain injury and NADPH oxidase: A deep relationship. Oxid Med Cell Longev 2015;2015:1-10.
  • 20 Simonyi A, Serfozo P, Lehmidi TM, Cui J, Gu Z, Lubahn DB, et al. The neuroprotective effects of apocynin. Front Biosci (Elite Ed) 2012;4:2183-93.
  • 21 Hatic H, Kane MJ, Saykally JN, Citron BA. Modulation of transcription factor Nrf2 in anin vitro model of traumatic brain injury. J Neurotrauma 2012;29:1188-96.
  • 22 Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB,et al. Pathophysiology associated with traumatic brain injury: Current treatments and potential novel therapeutics. Cell Mol Neurobiol 2017;37:571-85.
  • 23 Kovac S, Angelova PR, Holmström KM, Zhang Y, Dinkova-Kostova AT, Abramov AY. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim Biophys Acta 2015;1850:794-801.
  • 24 Hong Y, Yan W, Chen S, Sun CR, Zhang JM. The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice. Acta Pharmacol Sin 2010;31:1421-30.
  • 25 Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6-15.
  • 26 Lu XY, Wang HD, Xu JG, Ding K, Li T. NADPH oxidase inhibition improves neurological outcome in experimental traumatic brain injury. Neurochem Int 2014;69:14-9.
  • 27 Song SX, Gao JL, Wang KJ, Li R, Tian YX, Wei JQ, et al. Attenuation of brain edema and spatial learning deficits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats. Mol Med Rep 2013;7:327-31.
  • 28 Feng Y, Cui C, Liu X, Wu Q, Hu F, Zhang H, et al. Protective role of apocynin via suppression of neuronal autophagy and TLR4/NF-κB signaling pathway in a rat model of traumatic brain injury. Neurochem Res 2017;42:3296-309.
  • 29 Li T, Sun KJ, Wang HD, Zhou ML, Ding K, Lu XY, et al. Tert-butylhydroquinone ameliorates early brain injury after experimental subarachnoid hemorrhage in mice by enhancing Nrf2-independent autophagy. Neurochem Res 2015;40:1829-38.
  • 30 Boutten A, Goven D, Boczkowski J, Bonay M. Oxidative stress targets in pulmonary emphysema: Focus on the Nrf2 pathway. Expert Opin Ther Targets 2010;14:329-46.
  • 31 Ding H, Wang X, Wang H, Zhu L, Wang Q, Jia Y, et al. Nrf2-ARE signaling provides neuroprotection in traumatic brain injury via modulation of the ubiquitin proteasome system. Neurochem Int 2017;111:32-44.
  • 32 Ferreira AP, Rodrigues FS, Della-Pace ID, Mota BC, Oliveira SM, Velho Gewehr CD, et al. The effect of NADPH-oxidase inhibitor apocynin on cognitive impairment induced by moderate lateral fluid percussion injury: Role of inflammatory and oxidative brain damage. Neurochem Int 2013;63:583-93.
  • 33 Stefanska J, Sarniak A, Wlodarczyk A, Sokolowska M, Pniewska E, Doniec Z, et al. Apocynin reduces reactive oxygen species concentrations in exhaled breath condensate in asthmatics. Exp Lung Res 2012;38:90-9.
  • 34 Sargazi S, Jafari AM, Heidarpour M. Tert-butylhydroquinone (TBHQ) improves antioxiandt status in rat tissues following chronic diazinon intoxication. Iran J Veterinary Sci Technol 2015;2:42-52.