The Effect of Minocycline on MMP-9 Levels in Traumatic Brain Injury: An Experimental Study in Wistar Rats
DOI:
https://doi.org/10.3889/oamjms.2022.10469Keywords:
Traumatic brain injury, Minocycline, MMP-9, Experimental studyAbstract
Introduction
The matrix metalloproteinase-9 (MMP-9) inhibition is an important target in the treatment of traumatic brain injury. Recent studies have shown that Minocycline may have MMP-9 inhibition activity. This study aims to determine the effect of minocycline in inhibiting MMP-9 in cases of head injury which has not been studied much.
Methods
This research was conducted using a laboratory experimental method on rats with a post-test control group design. The research was conducted at the Animal Laboratory, Faculty of Medicine, Hasanuddin University for a period of 2 weeks. The research population was rats with traumatic brain injury and rats without traumatic brain injury as controls. The sample size for each group was determined with Federer's formula, the minimum number of samples for each group was 9 experimental animals (a total of 27 mice in this study). Group 1 are control group, group 2(TBI) are rats with a traumatic brain injury, and group 3 are rats with a traumatic brain injury who was given minocycline.
Results
The mean value of MMP-9 in group 2 (TBI) was 0.610116 ng/ml compared to the control mean value of 0.519300 ng/ml. The mean value of MMP-9 in group 3 (TBI+M) was 0.552674 ng/ml. From the ANOVA test, there was a significant relationship with a p-value = 0.001 There was a statistically significant relationship between the administration of minocycline and the decrease in MMP-9 levels in traumatic brain injury in Wistar rats.
Conclusion
The level of MMP-9 in Wistar rats with traumatic brain injury who were given minocycline was shown to be significantly lower than that of those without minocycline treatment. This result showed that minocycline has the potential to inhibit the increase of MMP-9 levels in traumatic brain injury.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Winkler EA, Minter D, Yue JK, Manley GT. Cerebral edema in traumatic brain injury, neurosurg: Pathophysiology and Prospective Therapeutic Targets. Neurosurg Clin N Am. 2016;27(4):473-88. https://doi.org/10.1016/j.nec.2016.05.008 PMid:27637397 DOI: https://doi.org/10.1016/j.nec.2016.05.008
Georges A, Das JM. Traumatic brain injury. In: StatPearls Publishing, Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459300/?report=classic [Last accessed on 2022 Mar 05].
Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol. 2017;357:577619. https://doi.org/10.1016/j.jneuroim.2021.577619 PMid:34058510 DOI: https://doi.org/10.1016/j.jneuroim.2021.577619
Khan A, Prince M, Brayne C, Prina AM. Lifetime prevalence and factors associated with head injury among older people in low and middle income countries: A 10/66 Study. PLoS One. 2015;10(7):e0132229. https://doi.org/10.1371/journal.pone.0132229 PMid:26146992 DOI: https://doi.org/10.1371/journal.pone.0132229
Zeng JP, Jia LT, Jin X, Zheng JP, ZhangXW, Zhan RY. Emodin attenuates brain edema after traumatic brain injury in rats. Int J Clin Exp Med. 2017;10:15213-20.
Alluri H, Wilson RL, Shaji CA, Wiggins-Dohlvik K, Patel S, Liu Y, et al. Melatonin preserves blood-brain barrier integrity and permeability via matrix metalloproteinase-9 inhibition. PLoS One. 2016;11:e0154427. https://doi.org/10.1371/journal.pone.0154427 DOI: https://doi.org/10.1371/journal.pone.0154427
Nascimento GC, Rizzi E, Gerlach RF, Leite-Panissi CR. Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation. Braz J Med Biol Res. 2013;46:956-67. https://doi.org/10.1590/1414-431X20133138 PMid:24270905 DOI: https://doi.org/10.1590/1414-431X20133138
Shen LC, Chen YK, Lin LM, Shaw SY. Anti-invasion and anti-tumor growth effect of doxycycline treatment for human oral squamous-cell carcinoma--in vitro and in vivo studies. Oral Oncol. 2010;46(3):178-84. https://doi.org/10.1016/j.oraloncology.2009.11.013 PMid:20036604 DOI: https://doi.org/10.1016/j.oraloncology.2009.11.013
Daud KR, Islam AA, Ihwan A, Zainuddin AA, Faruk M. Oral doxycycline on the level of matrix metalloproteinase 9 in rat models experiencing traumatic brain injury. IIUM Med J Malaysia. 2021;20:11-6. https://doi.org/10.31436/imjm.v20i1.1773 DOI: https://doi.org/10.31436/imjm.v20i1.1773
Prihantono P, Syamsu SA, Smaradhania N, Ahmad M, Siagian NA, Lubis K, et al. Application of Scaevola taccada (Gaertn.) Roxb. Reduce pro-inflammatory cytokines interleukin-1β _in sprague dawley mice suffering from mastitis. Open Access Maced J Med Sci. 2020;8:423-7. https://doi.org/10.3889/oamjms.2020.4363 DOI: https://doi.org/10.3889/oamjms.2020.4363
Nasution RA, Islam AA, Hatta M, Prihantono, Massi MN, Warsinggih, et al. Effectiveness of CAPE in reducing vascular permeability after brain injury. Med Clín Práct. 2021;4:100229. https://doi.org/10.1016/j.mcpsp.2021.100229 DOI: https://doi.org/10.1016/j.mcpsp.2021.100229
Nasution RA, Islam AA, Hatta M, Prihantono, Turchan A, Nasrullah, et al. Role of CAPE in Reducing Oxidative Stress in Animal Models with Traumatic Brain Injury. Ann Med Surg. 2020;57:118-22. https://doi.org/10.1016/j.amsu.2020.07.036 DOI: https://doi.org/10.1016/j.amsu.2020.07.036
Higashida T, Kreipke CW, Rafols JA, Peng C, Schafer S, Schafer P, et al. The role of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury. J Neurosurg. 2011;114:92-101. https://doi.org/10.3171/2010.6.JNS10207 PMid:20617879 DOI: https://doi.org/10.3171/2010.6.JNS10207
Fan X, Lo EH, Wang X. Effects of minocycline plus tissue plasminogen activator combination therapy after focal embolic stroke in Type 1 diabetic rats. Stroke. 2013;44(3):745-52. https://doi.org/10.1161/STROKEAHA.111.000309 PMid:23422086 DOI: https://doi.org/10.1161/STROKEAHA.111.000309
Yan P, Zhu A, Liao F, Xiao Q, Kraft AW, Gonzales E, et al. Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid angiopathy. Stroke. 2015;46(6):1633-40. https://doi.org/10.1161/STROKEAHA.115.008582 PMid:25944329 DOI: https://doi.org/10.1161/STROKEAHA.115.008582
Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods. 1991;39(3):253-62. https://doi.org/10.1016/0165-0270(91)90104-8 DOI: https://doi.org/10.1016/0165-0270(91)90104-8
Hayashi T, Kaneko Y, Yu S, Bae E, Stahl CE, Kawase T, et al. Quantitative analyses of matrix metalloproteinase activity after traumatic brain injury in adult rats. Brain Res. 2009;1280:172-7. https://doi.org/10.1016/j.brainres.2009.05.040 PMid:19464272 DOI: https://doi.org/10.1016/j.brainres.2009.05.040
Webster KM, Sun M, Crack P, O’Brien TJ, Shultz AJ, Semple BD. Inflammation in epileptogenesis after traumatic brain injury. J Neuroinflammation. 2017;14(1):10. https://doi.org/10.1186/s12974-016-0786-1 PMid:28086980 DOI: https://doi.org/10.1186/s12974-016-0786-1
Vajtr D, Benada O, Kukacka J, Průša R, Houstava L, Ťoupalík P, et al. Correlation of ultrastructural changes of endothelial cells and astrocytes occurring during blood brain barrier damage after traumatic brain injury with biochemical markers of BBB leakage and inflammatory response. Physiol Res. 2009;58(2):263-8. https://doi.org/10.33549/physiolres.931253 PMid:18380546 DOI: https://doi.org/10.33549/physiolres.931253
Grossetete M, Phelps J, Arko L, Yonas H, Rosenberg GA. Elevation of matrix metalloproteinases 3 and 9 in cerebrospinal fluid and blood in patients with severe traumatic brain injury. Neurosurgery. 2009;65(4):702-8. https://doi.org/10.1227/01.NEU.0000351768.11363.48 PMid:19834375 DOI: https://doi.org/10.1227/01.NEU.0000351768.11363.48
Yang Z, Fan R, Sun P, Cui H, Peng W, Luo J, et al. Rhubarb attenuates cerebral edema via inhibition of the extracellular signal-regulated kinase pathway following traumatic brain injury in rats. Pharmacogn Mag. 2018;14(53):134-9. https://doi.org/10.4103/pm.pm_218_17 PMid:29576714 DOI: https://doi.org/10.4103/pm.pm_218_17
Chang JJ, Kim-Tenser M, Emanuel BA, Jones GM, Chapple K, Alikhani A, et al. Pourmotabbed, Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: A pilot study. Eur J Neurol. 2017;24(1):1384-91. https://doi.org/10.1111/ene.13403 PMid:28929560 DOI: https://doi.org/10.1111/ene.13403
Hanemaaijer R, van Lent N, Sorsa T, Salo T, YrjŐ, Konttinen T, et al. Inhibition of matrix metalloproteinases (MMPs) by tetracyclines. In: Nelson M, Hillen W, Greenwald RA, editors. BT-tetracyclines in Biology, Chemistry and Medicine. Switzerland: Birkhäuser Basel; 2001. p. 267-81. https://doi.org/10.1007/978-3-0348-8306-1_11 DOI: https://doi.org/10.1007/978-3-0348-8306-1_11
Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006;58:256-65. https://doi.org/10.1093/jac/dkl224 PMid:16816396 DOI: https://doi.org/10.1093/jac/dkl224
Fouda AY, Newsome AS, Spellicy S, Waller JL, Zhi W, Hess DC, et al. Minocycline in acute cerebral hemorrhage: An early phase randomized trial. Stroke. 2017;48(10):2885-7. https://doi.org/10.1161/STROKEAHA.117.018658 Mid:28887388 DOI: https://doi.org/10.1161/STROKEAHA.117.018658
Ding JY, Kreipke CW, Schafer P, Schafer S, Speirs SL, Rafols JA. Synapse loss regulated by matrix metalloproteinases in traumatic brain injury is associated with hypoxia inducible factor-1alpha expression. Brain Res. 2009;1268:125-34. https://doi.org/10.1016/j.brainres.2009.02.060 PMid:19285046 DOI: https://doi.org/10.1016/j.brainres.2009.02.060
Downloads
Published
How to Cite
License
Copyright (c) 2022 Darren Perdana, Andi Ihwan, Andi Alfian Zainuddin, Andi Asadul Islam, Djoko Widodo, Nasrullah Nasrullah, Willy Adhimarta, Wahyudi Wahyudi, Robert Christeven, Muhammad Faruk (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0
