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MRI 结合临床应用的氧化铁纳米颗粒显示脉络丛参与神经炎症的小鼠模型。

MRI coupled with clinically-applicable iron oxide nanoparticles reveals choroid plexus involvement in a murine model of neuroinflammation.

机构信息

Univ Lyon, CarMeN laboratory, Inserm U1060, INRA U1397, INSA Lyon, Université Claude Bernard Lyon 1, Lyon, France.

HCL, Lyon, France.

出版信息

Sci Rep. 2019 Jul 11;9(1):10046. doi: 10.1038/s41598-019-46566-1.

Abstract

Choroid plexus (ChPs) are involved in the early inflammatory response that occurs in many brain disorders. However, the activation of immune cells within the ChPs in response to neuroinflammation is still largely unexplored in-vivo. There is therefore a crucial need for developing imaging tool that would allow the non-invasive monitoring of ChP involvement in these diseases. Magnetic resonance imaging (MRI) coupled with superparamagnetic particles of iron oxide (SPIO) is a minimally invasive technique allowing to track phagocytic cells in inflammatory diseases. Our aim was to investigate the potential of ultrasmall SPIO (USPIO)-enhanced MRI to monitor ChP involvement in-vivo in a mouse model of neuroinflammation obtained by intraperitoneal administration of lipopolysaccharide. Using high resolution MRI, we identified marked USPIO-related signal drops in the ChPs of animals with neuroinflammation compared to controls. We confirmed these results quantitatively using a 4-points grading system. Ex-vivo analysis confirmed USPIO accumulation within the ChP stroma and their uptake by immune cells. We validated the translational potential of our approach using the clinically-applicable USPIO Ferumoxytol. MR imaging of USPIO accumulation within the ChPs may serve as an imaging biomarker to study ChP involvement in neuroinflammatory disorders that could be applied in a straightforward way in clinical practice.

摘要

脉络丛(ChPs)参与许多脑部疾病中发生的早期炎症反应。然而,在神经炎症中 ChPs 内免疫细胞的激活在很大程度上仍未被体内探索。因此,迫切需要开发一种成像工具,以便能够非侵入性地监测这些疾病中 ChP 的参与。磁共振成像(MRI)与超顺磁性氧化铁(SPIO)颗粒结合是一种微创技术,可用于跟踪炎症性疾病中的吞噬细胞。我们的目的是研究超小超顺磁氧化铁(USPIO)增强 MRI 在通过腹腔内给予脂多糖获得的神经炎症小鼠模型中体内监测 ChP 参与的潜力。使用高分辨率 MRI,我们在神经炎症动物的 ChPs 中与对照组相比,发现明显的 USPIO 相关信号下降。我们使用 4 分制评分系统对这些结果进行了定量确认。离体分析证实了 USPIO 在 ChP 基质内的积累及其被免疫细胞摄取。我们使用临床应用的 USPIO Ferumoxytol 验证了我们方法的转化潜力。ChPs 内 USPIO 积累的 MRI 可作为研究神经炎症性疾病中 ChP 参与的成像生物标志物,可在临床实践中直接应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e2e/6624288/3071f2b0151d/41598_2019_46566_Fig1_HTML.jpg

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