Background Traumatic brain injury (TBI) triggers potentially harmful chronic neuroinflammation. The antibiotic minocycline is neuroprotective in animal models of TBI through the inhibition of microglial activation. We used [11C]PBR28 positron emission tomography (PET) to test whether minocycline reduces microglial activation after TBI.
Methods Fifteen patients 6 months-11 years after a moderate-severe TBI and age-matched controls had MRI, neuropsychological testing and PET. Patients received either minocycline 100 mg orally twice daily or no drug (2:1 ratio) for 12 weeks, and were followed up at 12 weeks and 6 months.
Results In patients, [11C]PBR28 binding was increased in white matter (WM) and thalamus. Patients had MRI evidence of WM damage at baseline and also had longitudinal volume loss (mean, −1.6%/year). WM damage and atrophy were highest in areas of increased [11C]PBR28 binding. [11C]PBR28 binding after 12 weeks' minocycline was significantly reduced (e.g. mean WM volume of distribution change=−23.3%, 95% CI −40.9 to −5.6%), indicating a reduction in microglial activation.
Conclusion Progressive volume loss in white matter with high microglial activation indicates on-going neurodegeneration. Minocycline reduced [11C]PBR28 binding, suggesting a treatment effect on microglial activation. These findings support the case for further clinical evaluation of minocycline as a treatment for neurodegeneration after TBI.
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