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Treating Traumatic Brain Injury with Minocycline

  • Review
  • Published:
Neurotherapeutics

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.

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Acknowledgements

We thank Elena Nikulina and Riley Morrone for a critical reading of this manuscript.

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This work was funded by an award (NS108190) to P.J.B.

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  1. Graduate Programs in Neural and Behavioral Sciences, State University of New York Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, New York, NY, 11203, USA

    Peter J. Bergold, Rachel Furhang & Siobhán Lawless

  2. Department of Physiology and Pharmacology, State University of New York Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, New York, NY, 11203, USA

    Peter J. Bergold

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Bergold, P.J., Furhang, R. & Lawless, S. Treating Traumatic Brain Injury with Minocycline. Neurotherapeutics 20, 1546–1564 (2023). https://doi.org/10.1007/s13311-023-01426-9

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