Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage.
Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage.
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脑出血后神经保护性胶质瘢痕形成过程中小胶质细胞 - 星形胶质细胞相互作用的时间动态
DOI：
10.1016/j.jpha.2023.02.007
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发表时间：
2023-08
影响因子：
8.8
通讯作者：
Yu, Jun
中科院分区：
文献类型：
--
作者：
Zheng, Jingwei;Wu, Haijian;Wang, Xiaoyu;Zhang, Guoqiang;Lu, Jia'nan;Xu, Weilin;Xu, Shenbin;Fang, Yuanjian;Zhang, Anke;Shao, Anwen;Chen, Sheng;Zhao, Zhen;Zhang, Jianmin;Yu, Jun
脑出血(ICH)后胶质瘢痕的作用尚不清楚。本研究旨在研究小胶质细胞与星形胶质细胞的相互作用是否影响胶质瘢痕的形成，并探讨胶质瘢痕的特殊功能。我们使用药理学方法在脑出血的不同阶段诱导小胶质细胞枯竭，并研究小胶质细胞消融对星形细胞瘢痕形成的影响。用空间转录组学(ST)分析探讨小胶质细胞-星形胶质细胞相互作用中潜在的配体-受体对，并验证不同时期星形胶质细胞瘢痕的功能变化。在早期，持续的小胶质细胞耗竭导致星形细胞瘢痕组织紊乱，中性粒细胞浸润增加，组织修复受损。ST分析表明，小胶质细胞衍生的胰岛素样生长因子1(IGF1)通过激活雷帕霉素(MTOR)信号的机制靶点调控星形细胞瘢痕的形成。此外，重新填充小胶质细胞(RM)更强地激活了mTOR信号，促进了更具保护性的瘢痕形成。IGF1和骨桥蛋白(OPN)的联合作用是RM功能的必要条件和充分条件，而不是IGF1或OPN单独作用。在脑出血的慢性期，星形细胞瘢痕的整体净效应从保护性转变为破坏性，延迟的小胶质细胞耗竭可以部分逆转这一趋势。从我们的数据中收集到的重要见解是，持续的小胶质细胞耗竭可能不是早期脑出血的合理治疗策略。相反，早期IGF1/OPN联合晚期PLX3397治疗是一种有前景的治疗策略。这促使我们考虑小胶质细胞和星形胶质细胞复杂的时间动力学和整体净效应，并在脑出血后的精确时间点制定详细的治疗策略。脑出血后持续的小胶质细胞耗竭会导致星形细胞瘢痕的破坏。小胶质细胞来源的IGF1通过mTOR信号激活调节胶质瘢痕的形成。小胶质细胞的再生通过IGF1和OPN的结合促进组织修复。在脑出血慢性期，胶质瘢痕由保护转化为破坏。脑出血后应在精确的时间点实施精心的治疗策略。
The role of glial scar after intracerebral hemorrhage (ICH) remains unclear. This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar. We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation. Spatial transcriptomics (ST) analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods. During the early stage, sustained microglial depletion induced disorganized astrocytic scar, enhanced neutrophil infiltration, and impaired tissue repair. ST analysis indicated that microglia-derived insulin like growth factor 1 (IGF1) modulated astrocytic scar formation via mechanistic target of rapamycin (mTOR) signaling activation. Moreover, repopulating microglia (RM) more strongly activated mTOR signaling, facilitating a more protective scar formation. The combination of IGF1 and osteopontin (OPN) was necessary and sufficient for RM function, rather than IGF1 or OPN alone. At the chronic stage of ICH, the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this. The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH. Inversely, early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy. This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes, and develop elaborate treatment strategies at precise time points after ICH. Sustained microglial depletion induce disorganized astrocytic scar after ICH. Microglia-derived IGF1 modulates glial scar formation via mTOR signaling activation. Repopulating microglia facilitate tissue repair via the combination of IGF1 and OPN. The glial scar transforms from protection into destruction at chronic stage of ICH. The elaborate treatment strategies at precise time points should be implemented after ICH.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
M2小胶质细胞衍生的外泌体通过外泌体miR-124保护小鼠大脑免受缺血再灌注损伤
影响因子：
12.4
作者：
Li Z;Song Y;He T;Wen R;Li Y;Chen T;Huang S;Wang Y;Tang Y;Shen F;Tian HL;Yang GY;Zhang Z
通讯作者：
Zhang Z
影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
25
作者：
Hasel, Philip;Rose, Indigo V. L.;Liddelow, Shane A.
通讯作者：
Liddelow, Shane A.
DOI：
10.1016/s1474-4422(12)70104-7
发表时间：
2012-08
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Keep RF;Hua Y;Xi G
通讯作者：
Xi G