Precise control of embolic stroke with magnetized red blood cells in mice

• Published in: Communications biology Vol. 5; no. 1; p. 136
• Main Authors: Jin, Yuxiao, Shi, Peijun, Wang, Yu, Li, Jinghang, Zhang, Jiachen, Zhao, Xinxin, Ge, Yaping, Huang, Yanjie, Guo, Mengzhun, Wang, Feidi, Ci, Bo, Xiao, Xian, Gao, Xiaofei, Xu, Jianrong, Dang, Bobo, Ji, Botao, Ge, Woo-ping, Jia, Jie-Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-02-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/51; 14; 14/19; 14/28; 14/69; 59/57; 631/136/1425; 631/378/1689/534; 64/60; 692/699/375/1370/534; Age; Animal models; Biology; Biomedical and Life Sciences; Brain injury; Embolism; Embolisms; Erythrocytes; Hemorrhage; Ischemia; Life Sciences; Macrophages; Microglia; Mimicry; Nanoparticles; Reperfusion; Stroke; Transmission electron microscopy
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03082-9

Precise embolism control in immature brains can facilitate mechanistic studies of brain damage and repair after perinatal arterial ischemic stroke (PAIS), but it remains a technical challenge. Microhemorrhagic transformation is observed in one-third of infant patients who have suffered PAIS, but the underlying mechanism remains elusive. Building on an established approach that uses magnetic nanoparticles to induce PAIS, we develop a more advanced approach that utilizes magnetized erythrocytes to precisely manipulate
de novo
and in situ embolus formation and reperfusion in perinatal rodent brains. This approach grants spatiotemporal control of embolic stroke without any transarterial delivery of pre-formed emboli. Transmission electron microscopy revealed that erythrocytes rather than nanoparticles are the main material obstructing the vessels. Both approaches can induce microbleeds as an age-dependent complication; this complication can be prevented by microglia and macrophage depletion. Thus, this study provides an animal model mimicking perinatal embolic stroke and implies a potential therapeutic strategy for the treatment of perinatal stroke.
SIMPLE and SIMPLeR are proposed as models for embolism, the latter reversibly manipulating magnetized red blood cells to occlude cerebral vessels. Both methods induce age-dependent micro-hemorrhage transformation, with microglia/macrophage depletion preventing hemorrhage transformation.