Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury

Barry W. Festoff, Syed Ameenuddin, Paul M. Arnold, Andrea Wong, Karen S. Santacruz, Bruce A. Citron

Research output: Contribution to journalArticlepeer-review


Minocycline, a clinically used tetracycline for over 40 years, crosses the blood-brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase-3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor-α, as well as caspase-3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans.

Original languageEnglish (US)
Pages (from-to)1314-1326
Number of pages13
JournalJournal of Neurochemistry
Issue number5
StatePublished - Jun 2006
Externally publishedYes


  • Apoptosis
  • Caspase inhibition
  • Locomotor rating score
  • Tetracycline

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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