Efficacy of Minocycline in Neural Stem Cells Proliferation after Traumatic Brain Injury

Authors

  • R. R. Suzy Indharty Department of Neurosurgery, School of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia
  • Iskandar Japardi Department of Neurosurgery, School of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia
  • Andre M. P. Siahaan Department of Neurosurgery, School of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia
  • Steven Tandean Department of Neurosurgery, School of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia
  • Michael Lumintang Loe Department of Neurosurgery, School of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.3875

Keywords:

Brain-derived neurotropic factor, Minocycline, Neurogenesis, NF-E2-related factor 2, Traumatic brain injury, SOX2

Abstract

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that contributes to neurological impairments after traumatic brain injury (TBI). There is a robust evidence that neuroinflammation will diminish neurogenesis after TBI. Therefore, strategies to attenuate the inflammatory responses are potential to increase neurogenesis following TBI. Minocycline, a second-generation tetracycline antibiotic derivate, has potent anti-inflammatory effect by reducing microglial activation and suppressing some pro-inflammatory cytokines.

AIM: The aim of this study is to investigate if minocycline could enhance neurogenesis after TBI.

METHODS: Thirty Sprague Dawley rats were randomized into three treatments group, i.e., sham-operated controls, closed head injury (CHI), and CHI with minocycline. We used the modified Feeney’s weight-drop model for making CHI. For the treatment group, we gave minocycline per oral (50 mg/kg) twice daily for the first 2 days followed by 25 mg/kg once daily for 3 consecutive days. Animals were sacrificed on day 5. To assess the proliferation capacity of neural stem cells (NSC), we performed immunohistochemistry staining with SOX2, brain-derived neurotropic factor (BDNF), and NFR. Cell counts were carried out using light microscope with 1000 times magnification in 20 high-power fields.

RESULTS: SOX2, NF-E2-related factor 2 (NRF-2), and BDNF were upregulated in the CHI group compared to the sham-operated group (p < 0.05). NRF-2, BDNF, and SOX2 were upregulated also significantly in the CHI+ minocycline group compared to the sham-operated group and the CHI group (p < 0.05).

CONCLUSION: Minocycline increased the proliferation capacity of NSC.

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References

Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433-8. PMid:10688783

Kempermann G, Jessberger S, Steiner B, Kronenberg G. Milestones of neuronal development in the adult hippocampus. Trends Neurosci. 2004;27(8):447-52. https://doi.org/10.1016/j. tins.2004.05.013 PMid:15271491

Seki T. Microenvironmental elements supporting adult hippocampal neurogenesis. Anat Sci Int. 2003;78(2):69-78. https://doi.org/10.1046/j.0022-7722.2003.00043.x PMid:12828419

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(10):1683- 96. https://doi.org/10.1007/s00701-015-2512-7 PMid:26269030

Masel BE, DeWitt DS. Traumatic brain injury: A disease process, not an event. J Neurotrauma. 2010;27(8):1529-40. https://doi. org/10.1089/neu.2010.1358 PMid:20504161

Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4-9. PMid:17573392

Morganti-Kossmann MC, Satgunaseelan L, Bye N, Kossmann T. Modulation of immune response by head injury. Injury. 2007;38(12):1392-400. https://doi.org/10.1016/j. injury.2007.10.005 PMid:18048036

Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A. 2003;100(23):13632-7. https://doi. org/10.1073/pnas.2234031100 PMid:14581618

Kaur K, Kaur R, Kaur M. Recent advances in Alzheimer’s disease: Causes and treatment. Int J Pharm Pharm Sci. 2016;8(2):8-15.

Vallières L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci. 2002;22(2):486- 92. https://doi.org/10.1523/jneurosci.22-02-00486.2002 PMid:11784794

Elewa HF, Hilali H, Hess DC, Machado LS, Fagan SC. Minocycline for short-term neuroprotection. Pharmacotherapy. 2006;26(4):515-21. https://doi.org/10.1592/phco.26.4.515 PMid:16553511

Phukan P, Bawari M, Sengupta M. Promising neuroprotective plants from North-East India. Int J Pharm Pharm Sci. 2015;7(3):28-39.

Stirling DP, Khodarahmi K, Liu J, McPhail LT, McBride CB, Steeves JD, et al. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci. 2004;24(9):2182-90. https://doi.org/10.1523/ jneurosci.5275-03.2004 PMid:14999069

Teng YD, Choi H, Onario RC, Zhu S, Desilets FC, Lan S, et al. Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci U S A. 2004;101(9):3071-6. https://doi.org/10.1073/pnas.0306239101 PMid:14981254

Morimoto N, Shimazawa M, Yamashima T, Nagai H, Hara H. Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage. Brain Res. 2005;1044(1):8- 15. https://doi.org/10.1016/j.brainres.2005.02.062 PMid:15862784

Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004;4:7. https://doi.org/10.1186/1471-2377-4-7

PMid:15109399

Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci U S A. 2001;98(25):14669-74. https://doi.org/10.1073/ pnas.251341998 PMid:11724929

Siopi E, Cho AH, Homsi S, Croci N, Plotkine M, Marchand- Leroux C, et al. Minocycline restores sAPPα levels and reduces the late histopathological consequences of traumatic brain injury in mice. J Neurotrauma. 2011;28(10):2135-43. https://doi. org/10.1089/neu.2010.1738 PMid:21770756

Kelso ML, Scheff NN, Scheff SW, Pauly JR. Melatonin and minocycline for combinatorial therapy to improve functional and histopathological deficits following traumatic brain injury. Neurosci Lett. 2011;488(1):60-4. https://doi.org/10.1016/j. neulet.2010.11.003 PMid:21056621

Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21(8):2580-8. https://doi. org/10.1523/jneurosci.21-08-02580.2001 PMid:11306611

Krady JK, Basu A, Allen CM, Xu Y, LaNoue KF, Gardner TW, et al. Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes. 2005;54(5):1559-65. https:// doi.org/10.2337/diabetes.54.5.1559 PMid:15855346

Seabrook TJ, Jiang L, Maier M, Lemere CA. Minocycline affects microglia activation, abeta deposition, and behavior in APP-tg mice. Glia. 2006;53(7):776-82. https://doi.org/10.1002/ glia.20338 PMid:16534778

Fan LW, Pang Y, Lin S, Tien LT, Ma T, Rhodes PG, et al. Minocycline reduces lipopolysaccharide-induced neurological dysfunction and brain injury in the neonatal rat. J Neurosci Res. 2005;82(1):71-82. https://doi.org/10.1002/jnr.20623 PMid:16118791

Zanjani TM, Sabetkasaei M, Mosaffa N, Manaheji H, Labibi F, Farokhi B. Suppression of interleukin-6 by minocycline in a rat model of neuropathic pain. Eur J Pharmacol. 2006;538(1-3):66-72. https://doi.org/10.1016/j.ejphar.2006.03.063

PMid:16687137

Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW. Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis. Brain. 2002;125(Pt6):1297-308. https://doi.org/10.1093/brain/awf133 PMid:12023318

Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol. 2004;3(12):744- 51. https://doi.org/10.1016/s1474-4422(04)00937-8 PMid:15556807

Arvin KL, Han BH, Du Y, Lin SZ, Paul SM, Holtzman DM. Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol. 2002;52(1):54-61. https:// doi.org/10.1002/ana.10242 PMid:12112047

Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000;6(7):797-801. https://doi. org/10.1038/77528 PMid:10888929

Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002;417(6884):74-8. https://doi.org/10.1038/417074a PMid:11986668

Wixey JA, Reinebrant HE, Spencer SJ, Buller KM. Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotonergic system in the immature rat brain. Neuroscience. 2011;182:184-92. https://doi.org/10.1016/j.neuroscience.2011.03.033 PMid:21440046

Wang J, Wei Q, Wang CY, Hill WD, Hess DC, Dong Z. Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J Biol Chem. 2004;279(9):19948-54. https:// doi.org/10.1074/jbc.m313629200 PMid:15004018

Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly (ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci U S A. 2006;103(25):9685- 90. https://doi.org/10.1073/pnas.0600554103 PMid:16769901

Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, et al. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature. 2006;442(7104):823-6. https://doi.org/10.1038/nature04940 PMid:16799564

Guzman R, De Los Angeles A, Cheshier S, Choi R, Hoang S, Liauw J, et al. Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model. Stroke. 2008;39(4):1300-6. https://doi.org/10.1161/ strokeaha.107.500470 PMid:18309158

Nomoto H, Takaiwa M, Mouri A, Furukawa S. Pro-region of neurotrophins determines the processing efficiency. Biochem Biophys Res Commun. 2007;356(4):919-24. https://doi. org/10.1016/j.bbrc.2007.03.059 PMid:17395157

Cheng ZG, Zhang GD, Shi PQ, Du BS. Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury. Asian Pac J Trop Med. 2013;6(4):305-10. PMid:23608333

Zhang S, Cui W. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells. 2014;6(3):305-11. https://doi.org/10.4252/wjsc.v6.i3.305 PMid:25126380

Corenblum MJ, Ray S, Remley QW, Long M, Harder B, Zhang DD, et al. Reduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period. Aging Cell. 2016;15(4):725-36. https://doi.org/10.1111/ acel.12482 PMid:2709537564

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Published

2020-03-25

How to Cite

1.
Indharty RRS, Japardi I, Siahaan AMP, Tandean S, Loe ML. Efficacy of Minocycline in Neural Stem Cells Proliferation after Traumatic Brain Injury. Open Access Maced J Med Sci [Internet]. 2020 Mar. 25 [cited 2024 Nov. 23];8(A):59-64. Available from: https://oamjms.eu/index.php/mjms/article/view/3875

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