Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing, 400038, China.
Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Neurosci Bull. 2022 Oct;38(10):1199-1214. doi: 10.1007/s12264-022-00902-0. Epub 2022 Jul 11.
The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b pericytes after TBI. These CD11b pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
脑周细胞是血脑屏障 (BBB) 的独特且不可或缺的组成部分，并且有助于创伤性脑损伤 (TBI) 中的几种病理过程。然而，周细胞在受损大脑中受到调节的细胞和分子机制在很大程度上尚不清楚。在这里，我们表明中性粒细胞胞外诱捕网 (NETs) 的形成会在 TBI 后诱导出现 CD11b 周细胞。与 CD11b 周细胞相比，这些 CD11b 周细胞亚群的通透性和促炎特征增加。此外，NETs 中的组蛋白通过 Dectin-1 以 PKC-c-Jun 依赖的方式促进脑周细胞中 CD11b 的诱导，导致 TBI 后神经炎症和 BBB 功能障碍。这些数据表明，中性粒细胞-NET-周细胞和组蛋白-Dectin-1-CD11b 可能是周细胞激活和功能障碍的机制。靶向 NETs 形成和 Dectin-1 是治疗 TBI 的有前途的方法。
