Skip to main content
Top
Published in: Neurotherapeutics 6/2023

18-09-2023 | Review

Treating Traumatic Brain Injury with Minocycline

Authors: Peter J. Bergold, Rachel Furhang, Siobhán Lawless

Published in: Neurotherapeutics | Issue 6/2023

Login to get access

Summary

Traumatic brain injury (TBI) results in both rapid and delayed brain damage. The speed, complexity, and persistence of TBI present large obstacles to drug development. Preclinical studies from multiple laboratories have tested the FDA-approved anti-microbial drug minocycline (MINO) to treat traumatic brain injury. At concentrations greater than needed for anti-microbial action, MINO readily inhibits microglial activation. MINO has additional pleotropic effects including anti-inflammatory, anti-oxidant, and anti-apoptotic activities. MINO inhibits multiple proteins that promote brain injury including metalloproteases, caspases, calpain, and polyADP-ribose-polymerase-1. At these elevated doses, MINO is well tolerated and enters the brain even when the blood–brain barrier is intact. Most preclinical studies with a first dose of MINO at less than 1 h after injury have shown improved multiple outcomes after TBI. Fewer studies with more delayed dosing have yielded similar results. A small number of clinical trials for TBI have established the safety of MINO and suggested some drug efficacy. Studies are also ongoing that either improve MINO pharmacology or combine MINO with other drugs to increase its therapeutic efficacy against TBI. This review builds upon a previous, recent review by some of the authors (Lawless and Bergold, Neural Regen Res 17:2589–92, 2022). The present review includes the additional preclinical studies examining the efficacy of minocycline in preclinical TBI models. This review also includes recommendations for a clinical trial to test MINO to treat TBI.
Literature
1.
go back to reference Lawless S, Bergold PJ. Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine. Neural Regen Res. 2022;17(12):2589–92.PubMedPubMedCentralCrossRef Lawless S, Bergold PJ. Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine. Neural Regen Res. 2022;17(12):2589–92.PubMedPubMedCentralCrossRef
2.
go back to reference Faul M XL, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control Atlanta (GA). 2010. Faul M XL, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control Atlanta (GA). 2010.
3.
go back to reference Dixon KJ. Pathophysiology of traumatic brain injury. Phys Med Rehabil Clin N Am. 2017;28(2):215–25.PubMedCrossRef Dixon KJ. Pathophysiology of traumatic brain injury. Phys Med Rehabil Clin N Am. 2017;28(2):215–25.PubMedCrossRef
4.
go back to reference Hemlata, Vasudeva N, Sharma S. In-vivo and in-vitro investigations to assess traumatic brain injury. CNS Neurol Disord Drug Targets. 2023. Hemlata, Vasudeva N, Sharma S. In-vivo and in-vitro investigations to assess traumatic brain injury. CNS Neurol Disord Drug Targets. 2023.
5.
6.
go back to reference Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci. 2013;14(2):128–42. Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci. 2013;14(2):128–42.
7.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
9.
go back to reference Mohamadpour M, Whitney K, Bergold PJ. The importance of therapeutic time window in the treatment of traumatic brain injury. Front Neurosci. 2019;13:07.PubMedPubMedCentralCrossRef Mohamadpour M, Whitney K, Bergold PJ. The importance of therapeutic time window in the treatment of traumatic brain injury. Front Neurosci. 2019;13:07.PubMedPubMedCentralCrossRef
11.
go back to reference Somayaji MR, Przekwas AJ, Gupta RK. Combination therapy for multi-target manipulation of secondary brain injury mechanisms. Curr Neuropharmacol. 2018;16(4):484–504.PubMedPubMedCentralCrossRef Somayaji MR, Przekwas AJ, Gupta RK. Combination therapy for multi-target manipulation of secondary brain injury mechanisms. Curr Neuropharmacol. 2018;16(4):484–504.PubMedPubMedCentralCrossRef
12.
go back to reference Jonas M, Cunha BA. Minocycline. Therapeutic drug monitoring. 1982;4(2). Jonas M, Cunha BA. Minocycline. Therapeutic drug monitoring. 1982;4(2).
13.
go back to reference Garrido-Mesa N, Zarzuelo A, Galvez J. What is behind the non-antibiotic properties of minocycline? Pharmacol Res. 2013;67(1):18–30.PubMedCrossRef Garrido-Mesa N, Zarzuelo A, Galvez J. What is behind the non-antibiotic properties of minocycline? Pharmacol Res. 2013;67(1):18–30.PubMedCrossRef
14.
go back to reference Zhang L, Xiao H, Yu X, Deng Y. Minocycline attenuates neurological impairment and regulates iron metabolism in a rat model of traumatic brain injury. Arch Biochem Biophys. 2020;682: 108302.PubMedCrossRef Zhang L, Xiao H, Yu X, Deng Y. Minocycline attenuates neurological impairment and regulates iron metabolism in a rat model of traumatic brain injury. Arch Biochem Biophys. 2020;682: 108302.PubMedCrossRef
15.
go back to reference Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006;58(2):256–65.PubMedCrossRef Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006;58(2):256–65.PubMedCrossRef
16.
go back to reference Romero-Miguel D, Lamanna-Rama N, Casquero-Veiga M, Gómez-Rangel V, Desco M, Soto-Montenegro ML. Minocycline in neurodegenerative and psychiatric diseases: an update. Eur J Neurol. 2021;28(3):1056–81.PubMedCrossRef Romero-Miguel D, Lamanna-Rama N, Casquero-Veiga M, Gómez-Rangel V, Desco M, Soto-Montenegro ML. Minocycline in neurodegenerative and psychiatric diseases: an update. Eur J Neurol. 2021;28(3):1056–81.PubMedCrossRef
17.
go back to reference Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Exp Neurol. 2016;275 Pt 3(Pt 3):367–80. Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Exp Neurol. 2016;275 Pt 3(Pt 3):367–80.
18.
go back to reference Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery. 2001;48(6):1393–9; discussion 9–401. Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery. 2001;48(6):1393–9; discussion 9–401.
19.
go back to reference Bye N, Habgood MD, Callaway JK, Malakooti N, Potter A, Kossmann T, et al. Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration. Exp Neurol. 2007;204(1):220–33.PubMedCrossRef Bye N, Habgood MD, Callaway JK, Malakooti N, Potter A, Kossmann T, et al. Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration. Exp Neurol. 2007;204(1):220–33.PubMedCrossRef
20.
go back to reference Homsi S, Federico F, Croci N, Palmier B, Plotkine M, Marchand-Leroux C, et al. Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res. 2009;1291:122–32.PubMedCrossRef Homsi S, Federico F, Croci N, Palmier B, Plotkine M, Marchand-Leroux C, et al. Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res. 2009;1291:122–32.PubMedCrossRef
21.
go back to reference Siopi E, Cho AH, Homsi S, Croci N, Plotkine M, Marchand-Leroux C, et al. Minocycline restores sAPPalpha levels and reduces the late histopathological consequences of traumatic brain injury in mice. J Neurotrauma. 2011;28(10):2135–43.PubMedCrossRef Siopi E, Cho AH, Homsi S, Croci N, Plotkine M, Marchand-Leroux C, et al. Minocycline restores sAPPalpha levels and reduces the late histopathological consequences of traumatic brain injury in mice. J Neurotrauma. 2011;28(10):2135–43.PubMedCrossRef
22.
go back to reference Haber M, Abdel Baki SG, Grin’kina NM, Irizarry R, Ershova A, Orsi S, et al. Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury. Exp Neurol. 2013;249:169–77.PubMedCrossRef Haber M, Abdel Baki SG, Grin’kina NM, Irizarry R, Ershova A, Orsi S, et al. Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury. Exp Neurol. 2013;249:169–77.PubMedCrossRef
23.
go back to reference Lam TI, Bingham D, Chang TJ, Lee CC, Shi J, Wang D, et al. Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury. Neurorehabil Neural Repair. 2013;27(9):889–99.PubMedCrossRef Lam TI, Bingham D, Chang TJ, Lee CC, Shi J, Wang D, et al. Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury. Neurorehabil Neural Repair. 2013;27(9):889–99.PubMedCrossRef
24.
go back to reference Lopez-Rodriguez AB, Siopi E, Finn DP, Marchand-Leroux C, Garcia-Segura LM, Jafarian-Tehrani M, et al. CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cereb Cortex. 2015;25(1):35–45.PubMedCrossRef Lopez-Rodriguez AB, Siopi E, Finn DP, Marchand-Leroux C, Garcia-Segura LM, Jafarian-Tehrani M, et al. CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cereb Cortex. 2015;25(1):35–45.PubMedCrossRef
25.
go back to reference Hanlon LA, Huh JW, Raghupathi R. Minocycline transiently reduces microglia/macrophage activation but exacerbates cognitive deficits following repetitive traumatic brain injury in the neonatal rat. J Neuropathol Exp Neurol. 2016;75(3):214–26.PubMedPubMedCentralCrossRef Hanlon LA, Huh JW, Raghupathi R. Minocycline transiently reduces microglia/macrophage activation but exacerbates cognitive deficits following repetitive traumatic brain injury in the neonatal rat. J Neuropathol Exp Neurol. 2016;75(3):214–26.PubMedPubMedCentralCrossRef
26.
go back to reference Haber M, James J, Kim J, Sangobowale M, Irizarry R, Ho J, et al. Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes, and modifies neuroinflammation in a rat model of mild traumatic brain injury. J Cereb Blood Flow Metab. 2017;0(0):0271678X17718106. Haber M, James J, Kim J, Sangobowale M, Irizarry R, Ho J, et al. Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes, and modifies neuroinflammation in a rat model of mild traumatic brain injury. J Cereb Blood Flow Metab. 2017;0(0):0271678X17718106.
27.
go back to reference Wang JY, Bakhadirov K, Abdi H, Devous MD Sr, CD MdlP, Moore C, et al. Longitudinal changes of structural connectivity in traumatic axonal injury. Neurology. 2011;77(9):818–26. Wang JY, Bakhadirov K, Abdi H, Devous MD Sr, CD MdlP, Moore C, et al. Longitudinal changes of structural connectivity in traumatic axonal injury. Neurology. 2011;77(9):818–26.
28.
go back to reference Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013;4(3):e525–e. Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013;4(3):e525–e.
29.
go back to reference Witcher KG, Bray CE, Chunchai T, Zhao F, O’Neil SM, Gordillo AJ, et al. Traumatic brain injury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia. J Neurosci. 2021;41(7):1597–616.PubMedPubMedCentralCrossRef Witcher KG, Bray CE, Chunchai T, Zhao F, O’Neil SM, Gordillo AJ, et al. Traumatic brain injury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia. J Neurosci. 2021;41(7):1597–616.PubMedPubMedCentralCrossRef
30.
go back to reference Ritzel RM, Li Y, Jiao Y, Lei Z, Doran SJ, He J, et al. Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration. Sci Adv. 2023;9(10):eadd1101. Ritzel RM, Li Y, Jiao Y, Lei Z, Doran SJ, He J, et al. Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration. Sci Adv. 2023;9(10):eadd1101.
31.
go back to reference Kovesdi E, Kamnaksh A, Wingo D, Ahmed F, Grunberg NE, Long JB, Kasper CE, Agoston DV. Acute Minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury. Frontiers in Neurol. 2012;3(111). Kovesdi E, Kamnaksh A, Wingo D, Ahmed F, Grunberg NE, Long JB, Kasper CE, Agoston DV. Acute Minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury. Frontiers in Neurol. 2012;3(111).
32.
go back to reference He J, Mao J, Hou L, Jin S, Wang X, Ding Z, et al. Minocycline attenuates neuronal apoptosis and improves motor function after traumatic brain injury in rats. Exp Anim. 2021. He J, Mao J, Hou L, Jin S, Wang X, Ding Z, et al. Minocycline attenuates neuronal apoptosis and improves motor function after traumatic brain injury in rats. Exp Anim. 2021.
33.
go back to reference Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke. 2011;42(12):3587–93.PubMedPubMedCentralCrossRef Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke. 2011;42(12):3587–93.PubMedPubMedCentralCrossRef
34.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
35.
go back to reference Naderi Y, Panahi Y, Barreto GE, Sahebkar A. Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review. Neural Regen Res. 2020;15(5):773–82.PubMedCrossRef Naderi Y, Panahi Y, Barreto GE, Sahebkar A. Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review. Neural Regen Res. 2020;15(5):773–82.PubMedCrossRef
36.
go back to reference Sonmez E, Kabatas S, Ozen O, Karabay G, Turkoglu S, Ogus E, et al. Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat. Spine (Phila Pa 1976). 2013;38(15):1253–9. Sonmez E, Kabatas S, Ozen O, Karabay G, Turkoglu S, Ogus E, et al. Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat. Spine (Phila Pa 1976). 2013;38(15):1253–9.
37.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
38.
go back to reference Pernici CD, Rowe RK, Doughty PT, Madadi M, Lifshitz J, Murray TA. Longitudinal optical imaging technique to visualize progressive axonal damage after brain injury in mice reveals responses to different minocycline treatments. Sci Rep. 2020;10(1):7815.PubMedPubMedCentralCrossRef Pernici CD, Rowe RK, Doughty PT, Madadi M, Lifshitz J, Murray TA. Longitudinal optical imaging technique to visualize progressive axonal damage after brain injury in mice reveals responses to different minocycline treatments. Sci Rep. 2020;10(1):7815.PubMedPubMedCentralCrossRef
39.
go back to reference Vonder Haar C, Anderson GD, Elmore BE, Moore LH, Wright AM, Kantor ED, Farin FM, Bammler TK, MacDonald JW, Hoane MR. Comparison of the effect of minocycline and simvastatin on functional recovery and gene expression in a rat traumatic brain injury model. J Neurotrauma. 2014;31:961–75. Vonder Haar C, Anderson GD, Elmore BE, Moore LH, Wright AM, Kantor ED, Farin FM, Bammler TK, MacDonald JW, Hoane MR. Comparison of the effect of minocycline and simvastatin on functional recovery and gene expression in a rat traumatic brain injury model. J Neurotrauma. 2014;31:961–75.
40.
go back to reference Sheng WW, Zhang WP, Wang ML, Zhang SH, Hu H, Chu SL, et al. Incomplete protective effects of minocycline on traumatic brain injury in rats and mice. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006;35(4):411–8.PubMed Sheng WW, Zhang WP, Wang ML, Zhang SH, Hu H, Chu SL, et al. Incomplete protective effects of minocycline on traumatic brain injury in rats and mice. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006;35(4):411–8.PubMed
41.
go back to reference Ng SY, Semple BD, Morganti-Kossmann MC, Bye N. Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice. J Neurotrauma. 2012;29:1410–25.PubMedCrossRef Ng SY, Semple BD, Morganti-Kossmann MC, Bye N. Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice. J Neurotrauma. 2012;29:1410–25.PubMedCrossRef
42.
go back to reference Simon DW, Aneja RK, Alexander H, Bell MJ, Bayır H, Kochanek PM, Clark RS. Minocycline attenuates high mobility group box 1 translocation, microglial activation, and thalamic neurodegeneration after traumatic brain injury in postnatal day 17 rats. J Neurotrauma. 2017;ahead of print. Simon DW, Aneja RK, Alexander H, Bell MJ, Bayır H, Kochanek PM, Clark RS. Minocycline attenuates high mobility group box 1 translocation, microglial activation, and thalamic neurodegeneration after traumatic brain injury in postnatal day 17 rats. J Neurotrauma. 2017;ahead of print.
43.
go back to reference Sangobowale MA, Grin’kina NM, Whitney K, Nikulina E, St Laurent-Ariot K, Ho JS, et al. Minocycline plus N-acetylcysteine reduce behavioral deficits and improve histology with a clinically useful time window. J Neurotrauma. 2018a;35(7):907–17.PubMedCrossRef Sangobowale MA, Grin’kina NM, Whitney K, Nikulina E, St Laurent-Ariot K, Ho JS, et al. Minocycline plus N-acetylcysteine reduce behavioral deficits and improve histology with a clinically useful time window. J Neurotrauma. 2018a;35(7):907–17.PubMedCrossRef
44.
go back to reference Abdel Baki SG, Schwab B, Haber M, Fenton AA, Bergold PJ. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats. PLoS ONE. 2010;5(8):e12490.PubMedPubMedCentralCrossRef Abdel Baki SG, Schwab B, Haber M, Fenton AA, Bergold PJ. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats. PLoS ONE. 2010;5(8):e12490.PubMedPubMedCentralCrossRef
45.
go back to reference Siopi E, Calabria S, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice. J Neurotrauma. 2012;29(2):354–61.PubMedCrossRef Siopi E, Calabria S, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice. J Neurotrauma. 2012;29(2):354–61.PubMedCrossRef
46.
go back to reference Homsi S, Piaggio T, Croci N, Noble F, Plotkine M, Marchand-Leroux C, et al. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neurotrauma. 2010;27(5):911–21.PubMedCrossRef Homsi S, Piaggio T, Croci N, Noble F, Plotkine M, Marchand-Leroux C, et al. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neurotrauma. 2010;27(5):911–21.PubMedCrossRef
47.
go back to reference Perumal V, Ravula AR, Shao N, Chandra N. Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model. J Otol. 2023;18(1):38–48.PubMedCrossRef Perumal V, Ravula AR, Shao N, Chandra N. Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model. J Otol. 2023;18(1):38–48.PubMedCrossRef
48.
go back to reference Pechacek KM, Reck AM, Frankot MA, Vonder HC. Minocycline fails to treat chronic traumatic brain injury-induced impulsivity and attention deficits. Exp Neurol. 2022;348:113924.PubMedCrossRef Pechacek KM, Reck AM, Frankot MA, Vonder HC. Minocycline fails to treat chronic traumatic brain injury-induced impulsivity and attention deficits. Exp Neurol. 2022;348:113924.PubMedCrossRef
49.
go back to reference Sangobowale M, Nikulina E, Bergold PJ. Minocycline plus N-acetylcysteine protect oligodendrocytes when first dosed 12 hours after closed head injury in mice. Neurosci Lett. 2018b;682:16–20.PubMedPubMedCentralCrossRef Sangobowale M, Nikulina E, Bergold PJ. Minocycline plus N-acetylcysteine protect oligodendrocytes when first dosed 12 hours after closed head injury in mice. Neurosci Lett. 2018b;682:16–20.PubMedPubMedCentralCrossRef
50.
go back to reference Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. stroke. J Cereb Circ. 2010;41(10):2283–7. Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. stroke. J Cereb Circ. 2010;41(10):2283–7.
51.
go back to reference Taylor AN, Tio DL, Paydar A, Sutton RL. Sex differences in thermal, stress, and inflammatory responses to minocycline administration in rats with traumatic brain injury. J Neurotrauma. 2018;35(4):630–8.PubMedCrossRef Taylor AN, Tio DL, Paydar A, Sutton RL. Sex differences in thermal, stress, and inflammatory responses to minocycline administration in rats with traumatic brain injury. J Neurotrauma. 2018;35(4):630–8.PubMedCrossRef
52.
go back to reference Koulaeinejad N, Haddadi K, Ehteshami S, Shafizad M, Salehifar E, Emadian O, et al. Effects of minocycline on neurological outcomes in patients with acute traumatic brain injury: a pilot study. Iran J Pharm Res. 2019;18(2):1086–96.PubMedPubMedCentral Koulaeinejad N, Haddadi K, Ehteshami S, Shafizad M, Salehifar E, Emadian O, et al. Effects of minocycline on neurological outcomes in patients with acute traumatic brain injury: a pilot study. Iran J Pharm Res. 2019;18(2):1086–96.PubMedPubMedCentral
53.
go back to reference Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, et al. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33(5):679–89.PubMedCrossRef Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, et al. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33(5):679–89.PubMedCrossRef
54.
go back to reference Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, et al. Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration. Brain. 2018;141(2):459–71.PubMedCrossRef Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, et al. Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration. Brain. 2018;141(2):459–71.PubMedCrossRef
55.
go back to reference Camara-Lemarroy C, Metz L, Kuhle J, Leppert D, Willemse E, Li DK, et al. Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels. Mult Scler. 2022;28(13):2081–9.PubMedPubMedCentralCrossRef Camara-Lemarroy C, Metz L, Kuhle J, Leppert D, Willemse E, Li DK, et al. Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels. Mult Scler. 2022;28(13):2081–9.PubMedPubMedCentralCrossRef
56.
go back to reference Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther. 1973;14(5):852–61.PubMedCrossRef Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther. 1973;14(5):852–61.PubMedCrossRef
57.
go back to reference Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John HR. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012;135(4):1224–36.PubMedCrossRef Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John HR. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012;135(4):1224–36.PubMedCrossRef
58.
go back to reference Fagan SC, Edwards DJ, Borlongan CV, Xu L, Arora A, Feuerstein G, et al. Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection. Exp Neurol. 2004;186(2):248–51.PubMedCrossRef Fagan SC, Edwards DJ, Borlongan CV, Xu L, Arora A, Feuerstein G, et al. Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection. Exp Neurol. 2004;186(2):248–51.PubMedCrossRef
59.
go back to reference Alshikho MJ, Zürcher NR, Loggia ML, Cernasov P, Reynolds B, Pijanowski O, et al. Integrated magnetic resonance imaging and [(11) C]-PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis. Ann Neurol. 2018;83(6):1186–97.PubMedPubMedCentralCrossRef Alshikho MJ, Zürcher NR, Loggia ML, Cernasov P, Reynolds B, Pijanowski O, et al. Integrated magnetic resonance imaging and [(11) C]-PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis. Ann Neurol. 2018;83(6):1186–97.PubMedPubMedCentralCrossRef
60.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
61.
go back to reference Whitney K, Nikulina E, Rahman SN, Alexis A, Bergold PJ. Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury. Exp Neurol. 2021;345: 113816.PubMedPubMedCentralCrossRef Whitney K, Nikulina E, Rahman SN, Alexis A, Bergold PJ. Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury. Exp Neurol. 2021;345: 113816.PubMedPubMedCentralCrossRef
62.
go back to reference Abdel Baki SG, Kao HY, Kelemen E, Fenton AA, Bergold PJ. A hierarchy of neurobehavioral tasks discriminates between mild and moderate brain injury in rats. Brain Res. 2009;1280:98–106. Abdel Baki SG, Kao HY, Kelemen E, Fenton AA, Bergold PJ. A hierarchy of neurobehavioral tasks discriminates between mild and moderate brain injury in rats. Brain Res. 2009;1280:98–106.
63.
go back to reference Shochat A, Abookasis D. Differential effects of early postinjury treatment with neuroprotective drugs in a mouse model using diffuse reflectance spectroscopy. Neurophotonics. 2015;2(1):015001. Shochat A, Abookasis D. Differential effects of early postinjury treatment with neuroprotective drugs in a mouse model using diffuse reflectance spectroscopy. Neurophotonics. 2015;2(1):015001.
64.
go back to reference Hanlon LA, Raghupathi R, Huh JW. Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat. Exp Neurol. 2017;290:1–14. Hanlon LA, Raghupathi R, Huh JW. Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat. Exp Neurol. 2017;290:1–14.
65.
go back to reference Chhor V, Moretti R, Le Charpentier T, Sigaut S, Lebon S, Schwendimann L, Oré MV, Zuiani C, Milan V, Josserand J, Vontell R, Pansiot J, Degos V, Ikonomidou C, Titomanlio L, Hagberg H, Gressens P, Fleiss B. Role of microglia in a mouse model of paediatric traumatic brain injury. Brain Behav Immun. 2017;63:197-209. Chhor V, Moretti R, Le Charpentier T, Sigaut S, Lebon S, Schwendimann L, Oré MV, Zuiani C, Milan V, Josserand J, Vontell R, Pansiot J, Degos V, Ikonomidou C, Titomanlio L, Hagberg H, Gressens P, Fleiss B. Role of microglia in a mouse model of paediatric traumatic brain injury. Brain Behav Immun. 2017;63:197-209.
66.
go back to reference Haber M, James J, Kim J, Sangobowale M, Irizarry R, Ho J, Nikulina E, Grin'kina NM, Ramadani A, Hartman I, Bergold PJ. Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes and modifies neuroinflammation in a rat model of mild traumatic brain injury. J Cereb Blood Flow Metab. 2018;38(8):1312–1326. Haber M, James J, Kim J, Sangobowale M, Irizarry R, Ho J, Nikulina E, Grin'kina NM, Ramadani A, Hartman I, Bergold PJ. Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes and modifies neuroinflammation in a rat model of mild traumatic brain injury. J Cereb Blood Flow Metab. 2018;38(8):1312–1326.
67.
go back to reference Simon DW, Aneja RK, Alexander H, Bell MJ, Bayır H, Kochanek PM, Clark RSB. Minocycline attenuates high mobility group box 1 translocation, microglial activation, and thalamic neurodegeneration after traumatic brain injury in post-natal day 17 rats. J Neurotrauma. 2018;35(1):130–138. Simon DW, Aneja RK, Alexander H, Bell MJ, Bayır H, Kochanek PM, Clark RSB. Minocycline attenuates high mobility group box 1 translocation, microglial activation, and thalamic neurodegeneration after traumatic brain injury in post-natal day 17 rats. J Neurotrauma. 2018;35(1):130–138.
68.
go back to reference Wang, B, Lin, W, Zhu, H Minocycline improves the recovery of nerve function and alleviates blood-brain barrier damage by inhibiting endoplasmic reticulum in traumatic brain injury mice model. Euro J Inflam. 2021;19. Wang, B, Lin, W, Zhu, H Minocycline improves the recovery of nerve function and alleviates blood-brain barrier damage by inhibiting endoplasmic reticulum in traumatic brain injury mice model. Euro J Inflam. 2021;19.
69.
go back to reference Hiskens, MI, Vella, RK, Schneiders, AG, Fenning, AS. Minocycline improves cognition and molecular measures of inflammation and neurodegeneration following repetitive mTBI. 2021; Brain Inj. 35(7):831–841. Hiskens, MI, Vella, RK, Schneiders, AG, Fenning, AS. Minocycline improves cognition and molecular measures of inflammation and neurodegeneration following repetitive mTBI. 2021; Brain Inj. 35(7):831–841.
70.
go back to reference Lu Q, Xiong J, Yuan Y, Ruan Z, Zhang Y, Chai B, Li L, Cai S, Xiao J, Wu Y, Huang P, Zhang H. Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4. Int J Biol Sci. 2022;18(1):441–458. Lu Q, Xiong J, Yuan Y, Ruan Z, Zhang Y, Chai B, Li L, Cai S, Xiao J, Wu Y, Huang P, Zhang H. Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4. Int J Biol Sci. 2022;18(1):441–458.
71.
go back to reference Celorrio M, Shumilov K, Payne C, Vadivelu S, Friess SH. Acute minocycline administration reduces brain injury and improves long-term functional outcomes after delayed hypoxemia following traumatic brain injury. Acta Neuropathol Commun. 2022;10(1):10. Celorrio M, Shumilov K, Payne C, Vadivelu S, Friess SH. Acute minocycline administration reduces brain injury and improves long-term functional outcomes after delayed hypoxemia following traumatic brain injury. Acta Neuropathol Commun. 2022;10(1):10.
72.
go back to reference Perumal V, Ravula AR, Agas A, Gosain A, Aravind A, Sivakumar PM, I SS, Sambath K, Vijayaraghavalu S, Chandra N. Enhanced targeted delivery of minocycline via transferrin conjugated albumin nanoparticle improves neuroprotection in a blast traumatic brain injury model. Brain Sci. 2023;13(3):402. Perumal V, Ravula AR, Agas A, Gosain A, Aravind A, Sivakumar PM, I SS, Sambath K, Vijayaraghavalu S, Chandra N. Enhanced targeted delivery of minocycline via transferrin conjugated albumin nanoparticle improves neuroprotection in a blast traumatic brain injury model. Brain Sci. 2023;13(3):402.
73.
go back to reference Perumal V, Ravula AR, Shao N, Chandra N. Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model. J Otol. 2023;18(1):38–48. Perumal V, Ravula AR, Shao N, Chandra N. Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model. J Otol. 2023;18(1):38–48.
74.
go back to reference Noriega-Navarro R, Martínez-Tapia RJ, González-Rivera R, Ochoa-Sánchez A, Abarca-Magaña JC, Landa-Navarro L, Rodríguez-Mata V, Ugalde-Muñiz P, Pérez-Torres A, Landa A, Navarro L. The effect of thioredoxin-1 in a rat model of traumatic brain injury depending on diurnal variation. Brain Behav. 2023;e3031. Noriega-Navarro R, Martínez-Tapia RJ, González-Rivera R, Ochoa-Sánchez A, Abarca-Magaña JC, Landa-Navarro L, Rodríguez-Mata V, Ugalde-Muñiz P, Pérez-Torres A, Landa A, Navarro L. The effect of thioredoxin-1 in a rat model of traumatic brain injury depending on diurnal variation. Brain Behav. 2023;e3031.
75.
go back to reference Bai X, Zhao N, Koupourtidou C, Fang LP, Schwarz V, Caudal LC, Zhao R, Hirrlinger J, Walz W, Bian S, Huang W, Ninkovic J, Kirchhoff F, Scheller A. In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury. Dev Cell. 2023;58(13):1153–1169.e5. Bai X, Zhao N, Koupourtidou C, Fang LP, Schwarz V, Caudal LC, Zhao R, Hirrlinger J, Walz W, Bian S, Huang W, Ninkovic J, Kirchhoff F, Scheller A. In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury. Dev Cell. 2023;58(13):1153–1169.e5.
76.
go back to reference Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, Reineke J, Peduzzi-Nelson J, Roskos PT. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33:679–689. Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, Reineke J, Peduzzi-Nelson J, Roskos PT. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33:679–689.
Metadata
Title
Treating Traumatic Brain Injury with Minocycline
Authors
Peter J. Bergold
Rachel Furhang
Siobhán Lawless
Publication date
18-09-2023
Publisher
Springer International Publishing
Published in
Neurotherapeutics / Issue 6/2023
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-023-01426-9

Other articles of this Issue 6/2023

Neurotherapeutics 6/2023 Go to the issue