Brain Center, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Second People's Hospital, Shenzhen, Guangdong, China.
Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Neurotrauma. 2020 Jan 1;37(1):43-54. doi: 10.1089/neu.2019.6460. Epub 2019 Sep 18.
Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.
小胶质细胞是中枢神经系统中的主要免疫细胞，在创伤性脑损伤（TBI）后会发生显著的形态和转录变化。然而，它们对 TBI 发病机制的确切贡献仍存在争议，有待阐明。在本研究中，thy-1 GFP 小鼠连续 21 天接受集落刺激因子 1 受体抑制剂（PLX3397）治疗，然后接受中度流体冲击损伤（FPI）。在 FPI 后 1 天和 3 天收集脑组织样本进行流式细胞术分析、免疫荧光、树突棘定量、末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定和 Western blot。我们发现 PLX3397 治疗显著降低了驻留小胶质细胞和浸润免疫细胞的比例。小胶质细胞耗竭促进了神经突生长，保存了树突棘，并减少了 FPI 后总脑细胞和神经元凋亡，同时内质网应激标志物蛋白、C/EBP 同源蛋白和需要肌醇的激酶 1α的蛋白水平也降低。总之，这些发现表明小胶质细胞耗竭可能在 FPI 的急性期发挥有益作用。
