外伤性脑损伤引起的体感皮层神经元损伤导致杆状小胶质细胞形成，从而促进星形胶质细胞增多和持续性神经炎症,Glia

当前位置： X-MOL 学术 › Glia › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

外伤性脑损伤引起的体感皮层神经元损伤导致杆状小胶质细胞形成，从而促进星形胶质细胞增多和持续性神经炎症
Glia ( IF 5.4 ) Pub Date : 2018-10-30 , DOI: 10.1002/glia.23523
Kristina G. Witcher ₁ , Chelsea E. Bray ₁ , Julia E. Dziabis ₁ , Daniel B. McKim ₁ , Brooke N. Benner ₁ , Rachel K. Rowe _{2,

3} , Olga N. Kokiko-Cochran _{1,

4} , Phillip G. Popovich _{1,

4,

5} , Jonathan Lifshitz _{2,

3} , Daniel S. Eiferman ₆ , Jonathan P. Godbout _{1,

4,

5}

Affiliation

小胶质细胞在对创伤性脑损伤（TBI）的免疫反应中经历动态的结构和转录变化。例如，TBI导致小胶质细胞在大脑皮层中形成杆状训练，但它们对炎症和病理生理的贡献尚不清楚。这项研究的目的是确定杆状小胶质细胞的起源和排列，并确定小胶质细胞在传播持续性皮层炎症中的作用。在这里，小鼠中的弥漫性TBI是通过中线液体撞击伤（FPI）建模的。骨髓嵌合体和BrdU脉冲追踪实验表明，棒状小胶质细胞来自常驻小胶质细胞，增殖有限。新数据还显示，TBI诱导的棒状小胶质细胞靠近轴突切除的神经元，在空间上与密集的星形胶质细胞增生重叠，并与顶角锥体树突对齐。此外，杆状小胶质细胞与肥大的小胶质细胞相邻形成，其在V层锥体神经元之间聚集。为了更好地了解小胶质细胞对皮质炎症和损伤的贡献，在TBI之前，通过CSF1R拮抗作用（PLX5622）消除了小胶质细胞。消除小胶质细胞不会影响TBI诱导的皮质神经元轴突切开术，但会减轻杆状小胶质细胞的形成和星形胶质细胞增生。对262个免疫基因的分析表明，TBI急性（8小时）引起了严重的皮质炎症，其自然和复杂性进展了7 dpi。例如，与补体，吞噬作用，toll样受体信号传导和干扰素反应相关的基因表达提高了7 dpi。至关重要的是，通过消除小胶质细胞可以预防这些急性和慢性炎症反应。在一起

"点击查看英文标题和摘要"

Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation

Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod‐shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse‐chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI‐induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll‐like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI‐induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.

更新日期：2018-10-30

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南