Department of Neurological Surgery, University of Florida, Gainesville, Florida 32610, USA.
Neurosurgery. 2010 Mar;66(3):544-50; discussion 550. doi: 10.1227/01.NEU.0000365616.46414.2B.
Although there are several large-species animal models for saccular aneurysms, there is a need for a simple, reproducible saccular aneurysm model in mice.
To develop a murine saccular aneurysm model, which replicates key characteristics that occur in the formation of human cerebral aneurysms.
Elastase is applied extravascularly to the right common carotid artery. We induced saccular aneurysm formation by our method in C57BL/6 mice (n = 30). Aneurysms and control arteries (left common carotid arteries) were harvested at 1 week, 2 weeks, and 3 weeks postinjury (n = 10 for each time point), measured, and stained for elastin content. To demonstrate BMP-derived cell recruitment to the aneurysms, bone marrow from UBC-gfp transgenic mice was transplanted into irradiated C57BL/6 recipients to create C57BL/6.gfp chimeras. Additionally, bone marrow from DsRed transgenic mice was transplanted into irradiated C57BL/6 recipients to create C57BL/6.DsRed chimeras, and bone marrow from B5/EGFP transgenic mice was transplanted into irradiated FVB recipients to create FVB.gfp chimeras. The elastase injury or sham operations were performed in the C57BL/6.gfp, C57BL/6.DsRed, and FVB.gfp chimeras. Aneurysms and sham vessels were harvested at 3 weeks and examined for BMP-derived cell recruitment. Additionally, aneurysms were stained for matrix metalloproteinase-9, which is overexpressed in human cerebral aneurysm tissue.
Aneurysms consistently demonstrated significant loss of elastin in the vessel wall and had significantly larger diameters than control vessels (591 +/- 238 microm vs 328 +/- 61 microm; P = .003 for aneurysms 3 weeks postinjury). Aneurysms from C57BL/6.gfp, FVB.gfp, and C57BL/6.DsRed chimeras consistently revealed significant BMP-derived cell recruitment in the aneurysm wall that was not seen in sham-operated vessels nor in control left common carotid arteries. Aneurysms demonstrated overexpression of matrix metalloproteinase-9.
We describe a novel murine elastase saccular aneurysm model that replicates the histopathology and BMP-derived cell-mediated processes that will be a valuable instrument for studying the cell-mediated processes in cerebral aneurysm formation.
尽管有几种大物种动物模型用于研究囊状动脉瘤，但仍需要一种简单、可重复的囊状动脉瘤小鼠模型。
建立一种囊状动脉瘤小鼠模型，该模型复制了人类脑动脉瘤形成过程中的关键特征。
将弹性酶外用于右侧颈总动脉。我们通过这种方法在 C57BL/6 小鼠中诱导囊状动脉瘤形成（n = 30）。在损伤后 1 周、2 周和 3 周时收获动脉瘤和对照动脉（左侧颈总动脉）（每个时间点 n = 10），测量并染色弹性蛋白含量。为了证明 BMP 衍生细胞募集到动脉瘤，将来自 UBC-gfp 转基因小鼠的骨髓移植到辐照的 C57BL/6 受者中，以创建 C57BL/6.gfp 嵌合体。此外，将来自 DsRed 转基因小鼠的骨髓移植到辐照的 C57BL/6 受者中，以创建 C57BL/6.DsRed 嵌合体，将来自 B5/EGFP 转基因小鼠的骨髓移植到辐照的 FVB 受者中，以创建 FVB.gfp 嵌合体。在 C57BL/6.gfp、C57BL/6.DsRed 和 FVB.gfp 嵌合体中进行弹性酶损伤或假手术。在 3 周时收获动脉瘤和假手术血管，并检查 BMP 衍生细胞募集情况。此外，还对基质金属蛋白酶-9 进行了染色，基质金属蛋白酶-9在人脑动脉瘤组织中过度表达。
动脉瘤始终显示出血管壁中弹性蛋白的显著丧失，并且其直径明显大于对照血管（损伤后 3 周时的动脉瘤为 591 ± 238 μm，对照血管为 328 ± 61 μm；P =.003）。C57BL/6.gfp、FVB.gfp 和 C57BL/6.DsRed 嵌合体的动脉瘤壁中始终显示出显著的 BMP 衍生细胞募集，而在假手术血管和对照左侧颈总动脉中均未观察到这种情况。动脉瘤表现出基质金属蛋白酶-9 的过度表达。
我们描述了一种新的小鼠弹性酶囊状动脉瘤模型，该模型复制了组织病理学和 BMP 衍生的细胞介导过程，这将是研究脑动脉瘤形成中细胞介导过程的一种有价值的工具。
