Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes and modifies neuroinflammation in a rat model of mild traumatic brain injury
Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes and modifies neuroinflammation in a rat model of mild traumatic brain injury
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DOI：
10.1177/0271678x17718106
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发表时间：
2018-08-01
影响因子：
6.3
通讯作者：
Bergold, Peter J.
中科院分区：
文献类型：
--
作者：
Haber, Margalit;James, Jessica;Bergold, Peter J.
每年有超过 200 万人遭受轻度创伤性脑损伤，但对于潜在的损伤却无能为力。美国食品和药物管理局批准的药物米诺环素加 N-乙酰半胱氨酸（MINO 加 NAC）可协同改善创伤性脑损伤大鼠轻度控制皮质冲击 (mCCI) 模型的认知和记忆。(3) 该药物组合的潜在细胞和分子机制尚不清楚。本研究探讨了药物组合对 mCCI 后白质损伤和神经炎症的影响。通过组织学和 qPCR 在四个时间点（损伤后 2、4、7 和 14 天）对接受假损伤、盐水、单独 MINO、单独 NAC 或 MINO 加 NAC 的 mCCI 大鼠的脑组织进行白质损伤和神经炎症标记物的研究。 MINO 和 NAC 协同保护常驻少突胶质细胞并减少少突胶质细胞前体细胞的数量。 MINO 加 NAC 治疗后两天，白质中小胶质细胞/巨噬细胞 (MP/MG) 的激活协同增加。治疗后 M1 和 M2 MP/MG 模式也发生改变。神经炎症的调节是促进髓鞘再生、改善认知和记忆的潜在机制。这些数据还为药物治疗如何诱导创伤性脑损伤后的修复提供了新的重要见解。
Mild traumatic brain injury afflicts over 2 million people annually and little can be done for the underlying injury. The Food and Drug Administration-approved drugs Minocycline plus N-acetylcysteine (MINO plus NAC) synergistically improved cognition and memory in a rat mild controlled cortical impact (mCCI) model of traumatic brain injury.(3) The underlying cellular and molecular mechanisms of the drug combination are unknown. This study addressed the effect of the drug combination on white matter damage and neuroinflammation after mCCI. Brain tissue from mCCI rats given either sham-injury, saline, MINO alone, NAC alone, or MINO plus NAC was investigated via histology and qPCR at four time points (2, 4, 7, and 14 days post-injury) for markers of white matter damage and neuroinflammation. MINO plus NAC synergistically protected resident oligodendrocytes and decreased the number of oligodendrocyte precursor cells. Activation of microglia/macrophages (MP/MG) was synergistically increased in white matter two days post-injury after MINO plus NAC treatment. Patterns of M1 and M2 MP/MG were also altered after treatment. The modulation of neuroinflammation is a potential mechanism to promote remyelination and improve cognition and memory. These data also provide new and important insights into how drug treatments can induce repair after traumatic brain injury.