Lawless S, Bergold PJ. Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine. Neural Regen Res. 2022;17(12):2589–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Dixon KJ. Pathophysiology of traumatic brain injury. Phys Med Rehabil Clin N Am. 2017;28(2):215–25.

Article  PubMed  Google Scholar 

Hemlata, Vasudeva N, Sharma S. In-vivo and in-vitro investigations to assess traumatic brain injury. CNS Neurol Disord Drug Targets. 2023.

Stocchetti N, Zanier ER. Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review. Crit Care. 2016;20(1):148.

Article  PubMed  PubMed Central  Google Scholar 

Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci. 2013;14(2):128–42.

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.

Article  PubMed  PubMed Central  Google Scholar 

Nie Z, Tan L, Niu J, Wang B. The role of regulatory necrosis in traumatic brain injury. Front Mol Neurosci. 2022;15:1005422.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohamadpour M, Whitney K, Bergold PJ. The importance of therapeutic time window in the treatment of traumatic brain injury. Front Neurosci. 2019;13:07.

Article  PubMed  PubMed Central  Google Scholar 

Garrido-Mesa N, Zarzuelo A, Galvez J. Minocycline: far beyond an antibiotic. Br J Pharmacol. 2013;169(2):337–52.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Somayaji MR, Przekwas AJ, Gupta RK. Combination therapy for multi-target manipulation of secondary brain injury mechanisms. Curr Neuropharmacol. 2018;16(4):484–504.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jonas M, Cunha BA. Minocycline. Therapeutic drug monitoring. 1982;4(2).

Garrido-Mesa N, Zarzuelo A, Galvez J. What is behind the non-antibiotic properties of minocycline? Pharmacol Res. 2013;67(1):18–30.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006;58(2):256–65.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Exp Neurol. 2016;275 Pt 3(Pt 3):367–80.

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.

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

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.

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.

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

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).

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.

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

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  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  CAS