Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using ¹¹C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, ¹¹C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater ¹¹C-PBR28 binding. Minocycline reduced ¹¹C-PBR28 binding (mean Δwhite matter binding = −23.30%, 95% confidence interval −40.9 to −5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.

中文翻译：

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米诺环素可减少脑外伤后的慢性小胶质细胞活化，但会增加神经退行性变

创伤性脑损伤的幸存者可能会在数年后恶化，发展为脑萎缩和痴呆。创伤性脑损伤会引发慢性小胶质细胞激活，但尚不清楚这是否有害或有益。创伤性脑损伤的成功慢性期治疗可能是针对小胶质细胞。在实验模型中，抗生素米诺环素抑制小胶质细胞活化。我们使用 PET、MRI 和血浆中轴突蛋白神经丝光的测量研究了米诺环素对小胶质细胞活化和神经变性的影响。^使用11评估小胶质细胞活化C-PBR28 PET。小胶质细胞激活与脑损伤测量的关系，以及米诺环素对疾病进展的影响，使用结构和扩散 MRI、血浆神经丝光和认知评估进行了评估。15 名患者在中度至重度脑外伤后至少 6 个月接受米诺环素 100 mg 每日两次口服或不服药，持续 12 周。在基线时，与对照组相比，患者在脑白质和丘脑中的^{11 C-PBR28 结合增加，血浆神经丝光水平升高。}白质损伤的 MRI 测量值在¹¹ C-PBR28 结合较大的区域最高。米诺环素¹¹C-PBR28 结合（平均 Δ白质结合 = -23.30%，95% 置信区间 -40.9 至 -5.64%，P = 0.018），但血浆神经丝光水平增加。在具有较高基线神经丝光水平的患者中发现更快的脑萎缩率。在这项实验医学研究中，创伤性脑损伤后的米诺环素减少了慢性小胶质细胞的激活，同时增加了神经变性的标志物。这些发现表明，小胶质细胞活化在创伤性脑损伤的慢性期具有修复作用。