Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.
Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.
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DOI：
10.1186/s12974-023-02932-5
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发表时间：
2023-11-15
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
脑微出血（CMH）与中风、认知能力下降和正常衰老有关。我们之前的研究表明，氧化应激红细胞（RBC）和脑内皮之间的相互作用可能是CMH发展的基础。然而，实时检测体内红细胞-脑内皮相互作用的改变，以及它们与红细胞清除、小胶质细胞反应和CMH发展的关系，尚未有报道。用过氧化叔丁基（t-BHP）对红细胞进行氧化应激，荧光标记并注射到成年Tie2-GFP小鼠中。使用体内双光子成像和离体共聚焦显微镜来评估与氧化应激RBC相关的红细胞-脑内皮相互作用的时间概况。它们与小胶质细胞活化和CMH的关系通过死后组织学检查。氧化应激小鼠脑血管红细胞迅速失速，血流速度下降，血流速度在第5天恢复。死后组织学证实，在注射t-必和必利蛋白处理的红细胞24小时后，红细胞与脑内皮细胞的相互作用和小胶质细胞的激活显著增强，并持续7天。此外，注射t-BHP-RBC后，在没有血脑屏障渗漏的情况下，显著的CMH发生。我们的体内和离体研究结果显示，脑毛细血管中氧化应激红细胞的延迟和清除，突出了小胶质细胞反应和红细胞-脑内皮相互作用改变在CMH发展中的重要性。我们的研究为CMH与红细胞-脑内皮相互作用增加的病理状况相关提供了新的机制见解。在线版本包含补充材料，可在10.1186/s12974-023-02932-5获得。
Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC–brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported. RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC–brain endothelial interactions associated with oxidatively stressed RBC. Their relationship with microglial activation and CMH was examined with post-mortem histology. Oxidatively stressed RBC stall significantly and rapidly in cerebral vessels in mice, accompanied by decreased blood flow velocity which recovers at 5 days. Post-mortem histology confirms significantly greater RBC–cerebral endothelial interactions and microglial activation at 24 h after t-BHP-treated RBC injection, which persist at 7 days. Furthermore, significant CMH develop in the absence of blood–brain barrier leakage after t-BHP-RBC injection. Our in vivo and ex vivo findings show the stalling and clearance of oxidatively stressed RBC in cerebral capillaries, highlighting the significance of microglial responses and altered RBC–brain endothelial interactions in CMH development. Our study provides novel mechanistic insight into CMH associated with pathological conditions with increased RBC–brain endothelial interactions. The online version contains supplementary material available at 10.1186/s12974-023-02932-5.
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影响因子：
8.3
作者：
Fisher MJ
通讯作者：
Fisher MJ
影响因子：
5.3
作者：
Karperien A;Ahammer H;Jelinek HF
通讯作者：
Jelinek HF
影响因子：
5.3
作者：
Catan, Aurelie;Turpin, Chloe;Meilhac, Olivier
通讯作者：
Meilhac, Olivier
影响因子：
4.9
作者：
Chang R;Al Maghribi A;Vanderpoel V;Vasilevko V;Cribbs DH;Boado R;Pardridge WM;Sumbria RK
通讯作者：
Sumbria RK
影响因子：
6.5
作者：
Hannemann A;Rees DC;Brewin JN;Noe A;Low B;Gibson JS
通讯作者：
Gibson JS