Modified murine intracranial aneurysm model: aneurysm formation and rupture by elastase and hypertension.
Modified murine intracranial aneurysm model: aneurysm formation and rupture by elastase and hypertension.
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DOI：
10.1136/neurintsurg-2013-010788
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发表时间：
2014-07
影响因子：
4.8
通讯作者：
Hoh BL
中科院分区：
文献类型：
--
作者：
Hosaka K;Downes DP;Nowicki KW;Hoh BL
脑动脉瘤的发生率高达5%。有几种动脉瘤的小鼠模型;然而，所有模型都有局限性，并且没有可重现的动脉瘤破裂模型。为了满足这一需求，我们修改了两个目前的啮齿动物动脉瘤模型，以创建一个可重复产生颅内动脉瘤和破裂的小鼠模型。在高血压饮食的C57 BL/6雌性小鼠中结扎左颈总动脉和右肾动脉。一周后，使用以下立体定向测量值，用立体定向框架创建小钻孔：前囟右侧1.2mm和0.7 mm外侧。 通过钻孔逐渐推进26 G针，直到与颅底接触，此时将针拉回0.3 mm。 将5、10和20 μL的10 U/mL弹性蛋白酶溶液和10 μL的1 U/mL弹性蛋白酶溶液立体定向注射到基底池中。 然后通过皮下放置的渗透泵以1000 ng/kg/min的剂量持续输注血管紧张素II。 对照组注射溴酚蓝溶液20 μL。 三周后，或如果小鼠在3周前死亡则更早，通过显微镜检查Willis环的动脉瘤形成和/或破裂迹象。 然后进行组织学分析，以评价弹性膜破坏、炎性细胞和巨噬细胞浸润、内膜内皮细胞缺失和动脉瘤壁内平滑肌层增厚。为了与人类动脉瘤进行比较，检查了人类动脉瘤标本（n=35; 34例未破裂和1例破裂）和正常对照颞浅动脉（STA）（n=9）。给予5、10和20 μL 10 U/mL弹性蛋白酶溶液的所有小鼠均在Willis环内形成颅内动脉瘤;分别有40%、60%和50%的小鼠动脉瘤破裂。 在给予10 μL 1.0 U/mL弹性蛋白酶溶液的小鼠中，90%发生颅内动脉瘤，20%发生动脉瘤破裂。 通过检查弹性膜的破坏来证实动脉瘤。动脉瘤一致地表现出CD 45阳性炎性细胞和F4/80阳性巨噬细胞浸润在动脉瘤壁内，这在正常假手术小鼠的Willis环中不存在。这些结果与人类动脉瘤和STA对照动脉中的结果相似。我们修改了两个目前的啮齿动物动脉瘤模型，以创建一个小鼠模型，产生一致的动脉瘤和破裂，可用于研究脑动脉瘤的形成，破裂和治疗。
Cerebral aneurysms occur in up to 5% of the population. There are several murine models of aneurysms; however, all have limitations and none reproducibly model aneurysm rupture. To fulfill this need, we modified two current rodent aneurysm models to create a murine model which reproducibly produces intracranial aneurysms and rupture. The left common carotid arteries and the right renal arteries were ligated in C57BL/6 female mice with a hypertensive diet. One week later, small burr holes were created with a stereotactic frame using the following stereotactic measurements: 1.2 mm rostral and 0.7 mm lateral to the right of the bregma. A 26 G needle was gradually advanced via the burr hole until contact with the skull base, upon which the needle was pulled back 0.3 mm. Five, 10 and 20 μL of 10 U/mL elastase solution and 10 μL of 1 U/mL elastase solution were stereotactically injected into the basal cisterns. Angiotensin II was then continually infused at a dose of 1000 ng/kg/min via an osmotic pump placed subcutaneously. In the control mice, 20 μL bromophenol blue solution was injected. Three weeks later, or earlier if mice expired prior to 3 weeks, the circle of Willis was inspected by microscopy for aneurysm formation and/or signs of rupture. Histological analyses were then performed to evaluate elastic lamina destruction, inflammatory cell and macrophage infiltration, absence of intimal endothelial cells and thickening of the smooth muscle layer within the aneurysm wall. To compare with human aneurysms, human aneurysm specimens (n=35; 34 unruptured and 1 ruptured) and normal control superficial temporal arteries (STAs) (n=9) were examined. All mice given 5, 10 and 20 μL of 10 U/mL elastase solution developed intracranial aneurysms within the circle of Willis; 40%, 60% and 50% of mice had ruptured aneurysms, respectively. In mice given 10 μL of 1.0 U/mL elastase solution, 90% developed intracranial aneurysms and 20% had ruptured aneurysms. Aneurysms were confirmed by examining the destruction of the elastic lamina. Aneurysms consistently demonstrated CD45 positive inflammatory cell and F4/80 positive macrophage infiltration within the aneurysm wall which was not present in the circle of Willis of normal sham-operated mice. These results were similar to those in human aneurysms and STA control arteries. We modified two current rodent aneurysm models to create a murine model that produces consistent aneurysms and rupture and can be used for studying cerebral aneurysm formation, rupture and treatment.
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影响因子：
--
作者：
Bavinzski, G;Al-Schameri, A;Richling, B
通讯作者：
Richling, B
影响因子：
3.8
作者：
Szymanski, Michael P.;Metaxa, Eleni;Meng, Hui;Kolega, John
通讯作者：
Kolega, John
影响因子：
5
作者：
Altes, TA;Cloft, HJ;Kallmes, DF
通讯作者：
Kallmes, DF
影响因子：
168.9
作者：
Wiebers, D;Whisnant, JP;Marler, JR
通讯作者：
Marler, JR
影响因子：
2.8
作者：
GUGLIELMI, G;JI, C;ROBERT, J
通讯作者：
ROBERT, J