Early-Stage Investigations of Ultrasmall Superparamagnetic Iron Oxide-Induced Signal Change After Permanent Middle Cerebral Artery Occlusion in Mice
Early-Stage Investigations of Ultrasmall Superparamagnetic Iron Oxide-Induced Signal Change After Permanent Middle Cerebral Artery Occlusion in Mice
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DOI：
10.1161/strokeaha.108.531269
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发表时间：
2009-05-01
期刊：
影响因子：
8.3
通讯作者：
Wiart, Marlene
中科院分区：
文献类型：
--
作者：
Desestret, Virginie;Brisset, Jean-Christophe;Wiart, Marlene
背景与目的：局灶性脑损伤亚急性期，静脉注射超顺磁氧化铁（USPIO）后mr信号变化与炎症细胞有关。然而，在早期阶段，与uspio相关的MR信号改变的解释仍然存在争议。在这里，我们比较了急性脑卒中啮齿类动物模型在静脉注射USPIO后的MR信号变化与24小时内的组织学铁和巨噬细胞分布。方法：对小鼠永久性大脑中动脉闭塞后6 ~ 24小时的7T多参数MRI和USPIO的组织学分布进行检测。采用钆磁共振成像和免疫球蛋白染色评估血脑屏障破坏情况。普鲁士蓝染色描绘USPIO脑分布。通过免疫化学对脑组织、外周血细胞和骨髓培养的单核细胞进行评估。结果：注射USPIO后，每幅MRI均可见4个早期信号改变区。在所有这些区域，无论是在血管和脑脊液室还是在间质中检测到的铁颗粒大多是游离的。在最初的24小时内，在损伤小鼠的血液中或与血浆浓度的USPIO孵育的单核细胞中均未检测到装载USPIO的细胞。结论-这些结果表明，在该模型中，早期可重复的USPIO相关MR信号变化主要是由血脑屏障渗漏后游离USPIO的被动扩散和血管内捕获引起的，而不是由外周吞噬细胞浸润引起的。（中风。2009;40:1834-1841）
Background and Purpose-MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke.Methods-Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood-brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture.Results-After USPIO injection, 4 areas of early signal change were observed on every MRI. In all these areas, iron particles were mostly free whether detected in the vascular and cerebrospinal fluid compartments or in the interstitium. Within the first 24 hours, USPIO- loaded cells were not detected in the blood of injured mice or in cultured monocytic cells incubated with USPIO at plasmatic concentration.Conclusions-These results suggest that, in this model, early reproducible USPIO- related MR signal changes are mainly caused by passive diffusion of free USPIO after blood-brain barrier leakage and by intravascular trapping rather than by peripheral phagocyte infiltration. (Stroke. 2009; 40: 1834-1841.)