Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury
Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury
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骨髓细胞 2 缺陷上表达的触发受体会改变急性巨噬细胞分布并改善脑外伤后的恢复
DOI：
10.1089/neu.2016.4401
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发表时间：
2017-01-15
影响因子：
4.2
通讯作者：
Lamb, Bruce T.
中科院分区：
文献类型：
--
作者：
Saber, Maha;Kokiko-Cochran, Olga;Lamb, Bruce T.
创伤性脑损伤（TBI）在美国每年影响170万人（疾病控制和预防中心）。越来越多的证据表明，暴露于TBI的人患多种神经退行性疾病的风险增加，包括阿尔茨海默病（AD）。TBI触发强烈的神经炎症反应，其特征在于星形胶质细胞增生、小胶质细胞活化和外周单核细胞浸润。最近的证据表明，先天免疫的改变促进神经退行性变。这包括遗传学研究，表明髓样细胞表达的触发受体2（TREM 2）的突变不仅与AD而且与多种神经退行性疾病的高风险相关。为了检查TREM 2缺陷是否影响TBI的病理结果，给予Trem 2敲除（Trem 2（-/-））和C57 BL/6 J（B6）小鼠侧向液压冲击损伤（FPI），并在损伤后3天和120天（DPI）处死以观察TREM 2缺陷的急性和慢性后果。值得注意的是，在3DPI时，暴露于TBI的B6小鼠在脑中表现出增加的TREM 2表达。此外，与暴露于TBI的B6小鼠相比，暴露于TBI的Trem 2（-/-）小鼠在病变附近表现出增强的巨噬细胞活化，但远离病变的巨噬细胞活化显著减少。此外，在120 DPI时，与暴露于TBI的B6小鼠相比，暴露于TBI的Trem 2（-/-）小鼠表现出减少的海马萎缩和TBI诱导的行为变化的拯救。总之，这项研究表明，TREM 2缺乏影响对TBI的急性和慢性反应，导致在早期时间点改变巨噬细胞反应，并在后期时间点改善病理和功能结果。
Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2(-/-)) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 days post-injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Further, Trem2(-/-) mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2(-/-) mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.