Skip to content
2000
Volume 23, Issue 9
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Spinal cord injury (SCI) has a catastrophic impact and lifelong functional incapacity on patients. Recent research has demonstrated the anti-inflammation and neuroprotection of minocycline, which were advantageous for treating disorders having an inflammatory foundation, including SCI. This study summarized the antioxidant, anti-inflammation, and neuro-restoration of minocycline. PubMed, Web of Science, Embase, and Chinese database were explored from their origin date to July 2022. Data extraction, methodological quality assessment, and study selection were conducted by 2 reviewers. Twenty-four studies were ultimately included. Overall, minocycline improved motor recovery after SCI, with Basso Beattie Bresnahan (BBB) scores in the treated group from the first week (15 studies, = 378; MD = 2.34; 95% Confidence interval (CI), 1.31-3.36; < 0.00001) to the fourth week (14 studies, = 346; MD = 3.15; 95% Confidence Interval (CI), 2.07-4.23; < 0.00001). Subgroup analysis showed function recovery was related to the mode of drug dose, animal race, and article quality. Network pharmacology identified 100 minocycline-related targets and 6720 SCI-related targets. Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Serine/Threonine kinase 1(Akt1), Steroid Receptor Coactivator (SRC), Epidermal growth factor receptor (EGFR) and Catenin (Cadherin-Associated Protein)-Beta 1 (CTNNB1) were key targets. 20 pathways were identified, including PI3K/Akt, MAPK and chemokine signaling pathway. Finally, molecular docking results showed B-cell CLL/lymphoma 2 (BCL2-6), CTNNB1, HSP90AA1, plasminogen activator urokinase (PLAU), and α protein kinase C alpha (PRCAKA) bound to minocycline better. This article concluded that minocycline was effective in treating SCI by improving neurological recovery and inhibiting oxidative stress, apoptosis, and inflammation.

Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X23666250313104646
2025-03-14
2025-10-13
Loading full text...

Full text loading...

References

  1. AhujaC.S. NoriS. TetreaultL. WilsonJ. KwonB. HarropJ. ChoiD. FehlingsM.G. Traumatic spinal cord injury-Repair and regeneration.Neurosurgery2017803SS9S2210.1093/neuros/nyw080 28350947
    [Google Scholar]
  2. KarsyM. HawrylukG. Modern medical management of spinal cord injury.Curr. Neurol. Neurosci. Rep.20191996510.1007/s11910‑019‑0984‑1 31363857
    [Google Scholar]
  3. DeVivoM.J. Causes and costs of spinal cord injury in the United States.Spinal Cord1997351280981310.1038/sj.sc.3100501 9429259
    [Google Scholar]
  4. SadowskyC.L. MargheritaA. The cost of spinal cord injury care.Spine199913593606
    [Google Scholar]
  5. Sandrow-FeinbergH.R. HouléJ.D. Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation.Brain Res.20151619122110.1016/j.brainres.2015.03.052 25866284
    [Google Scholar]
  6. Garrido-MesaN. ZarzueloA. GálvezJ. Minocycline: Far beyond an antibiotic.Br. J. Pharmacol.2013169233735210.1111/bph.12139 23441623
    [Google Scholar]
  7. YrjänheikkiJ. KeinänenR. PellikkaM. HökfeltT. KoistinahoJ. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia.Proc. Natl. Acad. Sci. USA19989526157691577410.1073/pnas.95.26.15769
    [Google Scholar]
  8. MorimotoN. ShimazawaM. YamashimaT. NagaiH. HaraH. Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage.Brain Res.20051044181510.1016/j.brainres.2005.02.062 15862784
    [Google Scholar]
  9. TikkaT. FiebichB.L. GoldsteinsG. KeinänenR. KoistinahoJ. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia.J. Neurosci.20012182580258810.1523/JNEUROSCI.21‑08‑02580.2001 11306611
    [Google Scholar]
  10. LeeJ.H.T. TigchelaarS. LiuJ. StammersA.M.T. StreijgerF. TetzlaffW. KwonB.K. Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury.Exp. Neurol.2010225121923010.1016/j.expneurol.2010.06.018 20599974
    [Google Scholar]
  11. KwonB.K. OkonE. HillyerJ. MannC. BaptisteD. WeaverL.C. FehlingsM.G. TetzlaffW. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury.J. Neurotrauma20112881545158810.1089/neu.2009.1149 20146558
    [Google Scholar]
  12. BassoD.M. FisherL.C. AndersonA.J. JakemanL.B. MctigueD.M. PopovichP.G. Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.J. Neurotrauma200623563565910.1089/neu.2006.23.635 16689667
    [Google Scholar]
  13. BassoD.M. BeattieM.S. BresnahanJ.C. A sensitive and reliable locomotor rating scale for open field testing in rats.J. Neurotrauma199512112110.1089/neu.1995.12.1 7783230
    [Google Scholar]
  14. MacleodM.R. O’CollinsT. HowellsD.W. DonnanG.A. Pooling of animal experimental data reveals influence of study design and publication bias.Stroke20043551203120810.1161/01.STR.0000125719.25853.20 15060322
    [Google Scholar]
  15. CangB. LiF. Effects of minocycline on motor function recovery after spinal cord crush injury in rats. English J.Practical Nervous Dis.201518163536
    [Google Scholar]
  16. DuanB. ZhouH. RenH. Minocycline up-regulates the expression of brain-derived neurotropic factor and neurotropin-3 in experimental incomplete spinal cord injury.Chin. J. Histochem. Cytochem.20132205406410
    [Google Scholar]
  17. TakedaM. KawaguchiM. KumatoriyaT. HoriuchiT. WatanabeK. InoueS. KonishiN. FuruyaH. Effects of minocycline on hind-limb motor function and gray and white matter injury after spinal cord ischemia in rats.Spine201136231919192410.1097/BRS.0b013e3181ffda29 21304434
    [Google Scholar]
  18. Xiao-boF.E.N.G. Hang-kongR.E.N. Effect of minocycline on the recovery of neurofunction in rats with incomplete spinal cord injury.Zhongguo Yiyuan Yaoxue Zazhi2012321074474710.13286/j.cnki.chinhosppharmacyj.2012.10.031
    [Google Scholar]
  19. GangW. XiaotaoW. ZubinM. Effect of minocycline on expression of cytochrome C and neuron apoptosis after spinal cord injury in rats.Chin. J Spine and Spinal Cord200620067523526
    [Google Scholar]
  20. Xiong-wei-yeH. Shao-dongZ. Jun-huaL. Bin-binW. Effect of minocycline on acute closed spinal cord injury in rats.Chin. J. Rehabil. Theory Prac.20192504416421
    [Google Scholar]
  21. Qian-longZ. Spermidine and Minocycline regulate ferroptosis after spinal cord injury in SD rats by inhibiting NO.202210.27811/d.cnki.gdixy.2022.000115
    [Google Scholar]
  22. PinzonA. MarcilloA. QuintanaA. StamlerS. BungeM.B. BramlettH.M. DietrichW.D. A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model.Brain Res.2008124314615110.1016/j.brainres.2008.09.047 18838063
    [Google Scholar]
  23. TanA.M. ZhaoP. WaxmanS.G. HainsB.C. Early microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury.J. Rehabil. Res. Dev.200946112313310.1682/JRRD.2008.03.0048 19533525
    [Google Scholar]
  24. FestoffB.W. AmeenuddinS. ArnoldP.M. WongA. SantacruzK.S. CitronB.A. Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury.J. Neurochem.200697513141326
    [Google Scholar]
  25. StirlingD.P. KhodarahmiK. LiuJ. McPhailL.T. McBrideC.B. SteevesJ.D. RamerM.S. TetzlaffW. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury.J. Neurosci.20042492182219010.1523/JNEUROSCI.5275‑03.2004 14999069
    [Google Scholar]
  26. SchmidtE.K.A. RaposoP.J.F. Torres-EspinA. FenrichK.K. FouadK. Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota.J. Neuroinflammation202118114410.1186/s12974‑021‑02123‑0 34174901
    [Google Scholar]
  27. SonmezE. KabatasS. OzenO. KarabayG. TurkogluS. OgusE. YilmazC. CanerH. AltinorsN. Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat.Spine201338151253125910.1097/BRS.0b013e3182895587 23370685
    [Google Scholar]
  28. SquairJ.W. RuizI. PhillipsA.A. ZhengM.M.Z. SarafisZ.K. SachdevaR. GopaulR. LiuJ. TetzlaffW. WestC.R. KrassioukovA.V. Minocycline reduces the severity of autonomic dysreflexia after experimental spinal cord injury.J. Neurotrauma201835242861287110.1089/neu.2018.5703 30113266
    [Google Scholar]
  29. SaganováK. OrendáčováJ. ČížkováD. VanickýI. Limited minocycline neuroprotection after balloon-compression spinal cord injury in the rat.Neurosci. Lett.2008433324624910.1016/j.neulet.2008.01.041 18280653
    [Google Scholar]
  30. AfsharyK. ChamanaraM. TalariB. RezaeiP. NassireslamiE. Therapeutic effects of minocycline pretreatment in the locomotor and sensory complications of spinal cord injury in an animal model.J. Mol. Neurosci.20207071064107210.1007/s12031‑020‑01509‑8 32144723
    [Google Scholar]
  31. LeeS.M. YuneT.Y. KimS.J. ParkD.W. LeeY.K. KimY.C. OhY.J. MarkelonisG.J. OhT.H. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat.J. Neurotrauma200320101017102710.1089/089771503770195867 14588118
    [Google Scholar]
  32. SencarL. YilmazD.M. TuliA. PolatS. Effects of combined treatment of minocycline and methylprednisolone on the expression of tumor necrosis factor alpha and interleukine-6 in experimental spinal cord injury: A light and electron microscopic study.Ultrastruct. Pathol.202044328329910.1080/01913123.2020.1771493 32567988
    [Google Scholar]
  33. ArasM. AltasM. MotorS. DokuyucuR. YilmazA. OzgirayE. SeraslanY. YilmazN. Protective effects of minocycline on experimental spinal cord injury in rats.Injury20154681471147410.1016/j.injury.2015.05.018 26052053
    [Google Scholar]
  34. TengY.D. ChoiH. OnarioR.C. ZhuS. DesiletsF.C. LanS. WoodardE.J. SnyderE.Y. EichlerM.E. FriedlanderR.M. Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury.Proc. Natl. Acad. Sci. USA200410193071307610.1073/pnas.0306239101 14981254
    [Google Scholar]
  35. UenoT. OhoriY. ItoJ. HoshikawaS. YamamotoS. NakamuraK. TanakaS. AkaiM. TobimatsuY. OgataT. Hyperphosphorylated neurofilament NF-H as a biomarker of the efficacy of minocycline therapy for spinal cord injury.Spinal Cord201149333333610.1038/sc.2010.116 20805831
    [Google Scholar]
  36. XuJ. JiJ. WangZ. XuT. Effects of minocycline on motor function recovery and expression of glial fibrillary acidic protein and brain-derived neurotrophic factor after spinal cord injury in rats.J. Pharm. Pharmacol.202173333233710.1093/jpp/rgaa041 33793886
    [Google Scholar]
  37. YuneT.Y. LeeJ.Y. JungG.Y. KimS.J. JiangM.H. KimY.C. OhY.J. MarkelonisG.J. OhT.H. Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury.J. Neurosci.200727297751776110.1523/JNEUROSCI.1661‑07.2007 17634369
    [Google Scholar]
  38. ZhangG. ZhaJ. LiuJ. DiJ. Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury.Arch. Med. Sci.201915247548310.5114/aoms.2018.73520 30899301
    [Google Scholar]
  39. IslamM.T. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.Neurol. Res.2017391738210.1080/01616412.2016.1251711 27809706
    [Google Scholar]
  40. Saed-MoucheshiA. SohrabiF. FasihfarE. BaniasadiF. RiasatM. MozafariA.A. Superoxide dismutase (SOD) as a selection criterion for triticale grain yield under drought stress: A comprehensive study on genomics and expression profiling, bioinformatics, heritability, and phenotypic variability.BMC Plant Biol.202121114810.1186/s12870‑021‑02919‑5 33752615
    [Google Scholar]
  41. ZelováH. HošekJ. TNF-α signalling and inflammation: Interactions between old acquaintances.Inflamm. Res.201362764165110.1007/s00011‑013‑0633‑0 23685857
    [Google Scholar]
  42. TanakaT. NarazakiM. KishimotoT. IL-6 in inflammation, immunity, and disease.Cold Spring Harb. Perspect. Biol.2014610a01629510.1101/cshperspect.a016295 25190079
    [Google Scholar]
  43. OrrM.B. GenselJ.C. Spinal cord injury scarring and inflammation: Therapies targeting glial and inflammatory responses.Neurotherapeutics201815354155310.1007/s13311‑018‑0631‑6 29717413
    [Google Scholar]
  44. GuadagnoJ. XuX. KarajgikarM. BrownA. CreganS.P. Microglia-derived TNFα induces apoptosis in neural precursor cells via transcriptional activation of the Bcl-2 family member Puma.Cell Death Dis.201343e53810.1038/cddis.2013.59 23492769
    [Google Scholar]
  45. PangT. WangJ. BenickyJ. SaavedraJ.M. Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition.Biochim. Biophys. Acta, Gen. Subj.20121820450351010.1016/j.bbagen.2012.01.011 22306153
    [Google Scholar]
  46. OlsonC.M. HedrickM.N. IzadiH. BatesT.C. OliveraE.R. AnguitaJ. p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens.Infect. Immun.200775127027710.1128/IAI.01412‑06 17074860
    [Google Scholar]
  47. DongH. ZhangX. DaiX. LuS. GuiB. JinW. ZhangS. ZhangS. QianY. Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1 pathway.J. Neuroinflammation201411114010.1186/s12974‑014‑0140‑4 25115727
    [Google Scholar]
  48. SticozziC. BelmonteG. MeiniA. CarbottiP. GrassoG. PalmiM. IL-1β induces GFAP expression in vitro and in vivo and protects neurons from traumatic injury-associated apoptosis in rat brain striatum via NFκB/Ca2+-calmodulin/ERK mitogen-activated protein kinase signaling pathway.Neuroscience201325236738310.1016/j.neuroscience.2013.07.061 23928073
    [Google Scholar]
  49. ZhaoL.X. JiangB.C. WuX.B. CaoD.L. GaoY.J. Ligustilide attenuates inflammatory pain via inhibition of NF κB-mediated chemokines production in spinal astrocytes.Eur. J. Neurosci.20143981391140210.1111/ejn.12502 24521480
    [Google Scholar]
  50. OrioL. LlopisN. TorresE. IzcoM. O’SheaE. ColadoM.I. A study on the mechanisms by which minocycline protects against MDMA (‘ecstasy’)-induced neurotoxicity of 5-HT cortical neurons.Neurotox. Res.201018218719910.1007/s12640‑009‑9120‑3 19777321
    [Google Scholar]
  51. Ataie-KachoieP. BadarS. MorrisD.L. PourgholamiM.H. Minocycline targets the NF-κB Nexus through suppression of TGF-β1-TAK1-IκB signaling in ovarian cancer.Mol. Cancer Res.201311101279129110.1158/1541‑7786.MCR‑13‑0239 23858099
    [Google Scholar]
  52. ZhongY. ShultzR.B. Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury.Neural Regen. Res.201712570271310.4103/1673‑5374.206633 28616020
    [Google Scholar]
  53. BetheaJ.R. Spinal cord injury-induced inflammation: A dual-edged sword.Prog. Brain Res.2000128334210.1016/S0079‑6123(00)28005‑9 11105667
    [Google Scholar]
  54. WhiteC. McCombeP.A. PenderM.P. Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95).Int. Immunol.199810793594110.1093/intimm/10.7.935 9701031
    [Google Scholar]
  55. BrásJP. BravoJ. FreitasJ. TNF-alpha-induced microglia activation requires miR-342: impact on NF-κB signaling and neurotoxicity.Cell Death Dis.202011641510.1038/s41419‑020‑2626‑6
    [Google Scholar]
  56. BeattieM.S. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury.Trends Mol. Med.2004101258058310.1016/j.molmed.2004.10.006 15567326
    [Google Scholar]
  57. BruckheimerE.M. ChoS.H. SarkissM. HerrmannJ. McDonnellT.J. The Bcl-2 gene family and apoptosis.Adv. Biochem. Eng. Biotechnol.1998627510510.1007/BFb0102306 9755641
    [Google Scholar]
  58. WangY. SunZ.Y. ZhangK.M. XuG.Q. LiG. Bcl-2 in suppressing neuronal apoptosis after spinal cord injury.World J. Emerg. Med.2011213844 25214981
    [Google Scholar]
  59. KaneD. SarafianT. AntonR. HahnH. GrallaE. ValentineJ. OrdT. BredesenD. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species.Science199326251371274127710.1126/science.8235659 8235659
    [Google Scholar]
  60. ZhongL.T. SarafianT. KaneD.J. CharlesA.C. MahS.P. EdwardsR.H. BredesenD.E. bcl-2 inhibits death of central neural cells induced by multiple agents.Proc. Natl. Acad. Sci. USA199390104533453710.1073/pnas.90.10.4533 8506295
    [Google Scholar]
  61. AllsoppT.E. WyattS. PatersonH.F. DaviesA.M. The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis.Cell199373229530710.1016/0092‑8674(93)90230‑N 8477446
    [Google Scholar]
  62. ThompsonC.D. ZurkoJ.C. HannaB.F. HellenbrandD.J. HannaA. The therapeutic role of interleukin-10 after spinal cord injury.J. Neurotrauma201330151311132410.1089/neu.2012.2651 23731227
    [Google Scholar]
  63. LvZ.C. CaoX.Y. GuoY.X. ZhangX.D. DingJ. GengJ. FengK. NiuH. MiR-137-5p alleviates inflammation by upregulating IL-10R1 expression in rats with spinal cord injury.Eur. Rev. Med. Pharmacol. Sci.201923114551455710.26355/eurrev_201906_18030 31210303
    [Google Scholar]
  64. YuF. SugawaraT. MaierC.M. HsiehL.B. ChanP.H. Akt/Bad signaling and motor neuron survival after spinal cord injury.Neurobiol. Dis.200520249149910.1016/j.nbd.2005.04.004 15896972
    [Google Scholar]
  65. AhmadK.A. ShoaibR.M. AhsanM.Z. DengM.Y. MaL. ApryaniE. LiX.Y. WangY.X. Microglial IL-10 and β-endorphin expression mediates gabapentinoids antineuropathic pain.Brain Behav. Immun.20219534436110.1016/j.bbi.2021.04.007 33862171
    [Google Scholar]
/content/journals/cn/10.2174/1570159X23666250313104646
Loading
/content/journals/cn/10.2174/1570159X23666250313104646
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test