NIR-II window tracking of hyperglycemia induced intracerebral hemorrhage in cerebral cavernous malformation deficient mice.

NIR-II window tracking of hyperglycemia induced intracerebral hemorrhage in cerebral cavernous malformation deficient mice.
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DOI:
10.1039/d0bm00873g
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发表时间:
2020-09-21
影响因子:
6.6
通讯作者:
--
中科院分区:
工程技术2区
文献类型:
--
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第二个近红外(NIR-II)窗口荧光成像在1000-1700 nm之间,减少了散射和自体荧光,以及深层组织光穿透,使早期和非侵入性确定血管病理。在这里,我们展示了体内近红外II成像技术,以跟踪高血糖诱导的脑出血和血脑屏障高通透性在脑海绵状畸形缺陷小鼠(CCM1+/−)。我们合成了聚乙二醇化的Ag2S量子点,在808 nm的近红外光下,荧光发射峰位于1135 nm处,用于动态成像小鼠的脑血管,并检测了高血糖CCM1+/−小鼠脑出血和血脑屏障损害的发生。体内光学成像分别用微型CT(包括k-均值聚类分析)和体内通透性测定(用FITC-葡聚糖灌注和免疫球蛋白染色)进行验证。进一步证实CCm1+/−小鼠血脑屏障通透性的增加与高糖引起的ccm1表达降低有关。本研究验证了深穿透性NIR-II量子点可用于脑血管异常转基因小鼠脑出血和血脑屏障高通透性的示踪。
Second near infrared (NIR-II) window fluorescence imaging between 1000–1700 nm with reduced scattering and autofluorescence, and deep tissue light penetration allows early and non-invasive determination of vascular pathologies. Here, we demonstrate in vivo NIR-II imaging techniques for tracking hyperglycaemia-induced Intracerebral Hemorrhage (ICH) and Blood Brain Barrier (BBB) hyperpermeability in Cerebral Cavernous Malformation (CCM) deficient mice (CCM1+/−). We synthesised PEGylated Ag2S quantum dots (QDs) with a bright fluorescent emission peak centred at 1135 nm under 808-nm NIR light for dynamic imaging of cerebral vasculature in mice and determined the development of ICH and BBB impairment in hyperglycaemic CCM1+/− mice. In vivo optical imaging was verified with micro-CT (including k-mean cluster analysis) as well as in vivo permeability assays using FITC-dextran perfusion and IgG staining, respectively. The increased BBB permeability in CCM1+/− mice was further demonstrated to be associated with high-glucose-caused decrease of CCM1 expression. This study validates that deep-penetrating NIR-II QDs can be used for the tracking of ICH and BBB hyperpermeability in transgenic mice models of cerebral vascular anomalies.
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