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Control of cerebral ischemia with magnetic nanoparticles
The precise manipulation of microcirculation in mice can facilitate mechanistic studies of brain injury and repair after ischemia, but this manipulation remains a technical challenge, particularly in conscious mice. We developed a technologythat uses micromagnets to induce aggregation of magnetic nanoparticles to reversibly occlude blood ow in microvessels. This allowed induction of ischemia in a specic cortical regionof conscious mice of any postnatal age, including perinatal and neonatal stages, with precise spatiotemporal control but without surgical intervention of the skull or artery. When combined with longitudinal live-imaging approaches, this technology facilitated the discovery of a feature of the ischemic cascade: selective loss of smooth muscle cells in juveniles but not adults shortly after onset of ischemia and during blood reperfusion.
Stroke is the second leading cause of death worldwide, killing nearly 6.7 million individuals each year. Of these individuals, 80% have accompanying ischemia that deprives brain cells of oxygen and nutrients1. To understand the molecular and cellular mechanisms of brain injury and repair after ischemic stroke, multiple approaches have been used to produce focal ischemia via occlusion mediated with a suture or ligation25, throm
botic blood clot emboli6,7, dye-induced photothrombosis (e.g., using Rose-Bengal or erythrosine B)810, and occlusion mediated through endothelin-1 (refs. 2,11,12). Furthermore, thrombosis can be introduced by inducing focal occlusion in single microvessels with a green or infrared laser1315. However, the
various procedures either require overly invasive surgery or do not allow precise control of reperfusion in blood vessels, especially in microvessels2,12,16. Hence, it remains challenging to induce focal ischemia that encompasses accurate manipulation of stroke size and duration of ischemia to probe the disruption of the neurongliavasculature network. Here, we report the development of an approach to induce focal ischemia with precise control of infarct size and occlusion duration. The occlusion, which is reversible, is achieved via micro
Jie-Min Jia1, Praveen D Chowdary2, Xiaofei Gao1, Bo Ci1, Wenjun Li3, Aditi Mulgaonkar4, Erik J Plautz5, Gedaa Hassan4, Amit Kumar4, Ann M Stowe5, Shao-Hua Yang3, Wei Zhou6, Xiankai Sun4, Bianxiao Cui2 & Woo-Ping Ge1,79
magnet-mediated aggregation of magnetic particles (MPs) within microvessels (Fig. 1ac). In combination with longitudinal live imaging, our approach allows the investigation of the disruption and repair of neurovascular units in vivo under...