大鼠实验性囊状动脉瘤生长塑形模型的建立

目的建立大鼠实验性囊状动脉瘤生长塑形模型。方法通过显微手术方法,破坏大鼠颈动脉分叉部位的内膜和内弹力层诱导囊性动脉瘤,在结扎及未结扎对侧颈总动脉的情况下,观察4-5个月,在长、宽、高三个径线上测量动脉瘤的大小,并行正常动脉和动脉瘤壁的组织学观察。结果通过显微手术方法直接破坏大鼠颈动脉分叉部位的内膜和内弹力层,成功诱导出囊状动脉瘤。经过4-5个月的血流冲击,动脉瘤的长、宽、高均明显增大(P<0.01),并且结扎对侧颈总动脉增加同侧血流冲击,可使动脉瘤在高度上继续增大(P<0.01)。正常动脉壁由内膜、中膜和外膜构成,各层结构保持完整。动脉瘤壁上没有内膜,结构排列紊乱,瘤壁变薄,有炎性细胞浸润。结论囊状动脉瘤在长期血流应力的作用下,逐渐增大生长塑形,提供了一个目前所知的较好的研究囊状动脉瘤生长塑形过程中血管生物学机制的动物模型。     

An acute experimental model of saccular aneurysms in the rat

A new and reproducible saccular aneurysm model has been developed at the bifurcation of the common carotid artery in rats. The details of the experimental methods and results are described. It is strongly suggested that the internal elastic lamina is a critical layer in saccular aneurysm formation, because an experimental saccular aneurysm can be produced immediately by transluminally damaging the inside of the arterial wall at the bifurcation of the common carotid artery. This saccular aneurysm model has several advantages: (i) it can be induced quickly and the success rate approaches 100% in rats; (ii) this technique can produce satisfactory experimental saccular aneurysms for other aneurysm studies, and in the future it will also be possible to use this technique to produce experimental saccular aneurysms in cerebral arteries of large animals.     

An acute experimental model of saccular aneurysms in the rat

A new and reproducible saccular aneurysm model has been developed at the bifurcation of the common carotid artery in rats. The details of the experimental methods and results are described. It is strongly suggested that the internal elastic lamina is a critical layer in saccular aneurysm formation, because an experimental saccular aneurysm can be produced immediately by transluminally damaging the inside of the arterial wall at the bifurcation of the common carotid artery. This saccular aneurysm model has several advantages: (i) it can be induced quickly and the success rate approaches 100% in rats; (ii) this technique can produce satisfactory experimental saccular aneurysms for other aneurysm studies, and in the future it will also be possible to use this technique to produce experimental saccular aneurysms in cerebral arteries of large animals.     

Animal model Of cerebral aneurysms: Pathology and pathogenesis of induced cerebral aneurysms in rats

Saccular cerebral aneurysms are induced in rats treated with ligation of one or both of the common carotid arteries, experimental hypertension, and β-aminopropionitrile feeding. Combination of ligation of the carotid artery and experimental hypertension is the minimal requirement for inducing aneurysms within a few months. β-aminopropionitrile makes the arterial wall fragile, increasing the incidence of aneurysmal development. Induced aneurysms are strongly related to haemodynamic stresses. They ere located on the large arteries at the base of the brain. Some of them apparently originate from the apex of bifurcation. The macroscopic and microscopic findings are generally in accordance with those of spontaneous lesions in man. The results of electron microscope and histochemical studies indicate the participation of leukocytes and their lysosomal enzymes in the development and growth of aneurysms. Adventitial cells are also suggested to be responsible for the growth of aneurysms.     

Cerebrovascular disease in Ehlers-Danlos syndrome type IV

We describe two patients with cerebrovascular complications of Ehlers-Danlos syndrome type IV. A 16-year-old girl with spontaneous internal carotid artery dissection and a 46-year-old woman with aneurysmal subarachnoid hemorrhage and multiple aortic dissections were both deficient in collagen type III, analyzed in cultured skin fibroblasts. To our knowledge, spontaneous carotid artery dissection associated with collagen type III deficiency has not been reported previously. Early clinical recognition of this syndrome is of great importance in view of the hazards of angiography and surgery. Collagen type III deficiency plays a role in the pathogenesis of intracranial saccular aneurysms and may also be involved in the pathogenesis of carotid cavernous fistulas and dissections of the cervical arteries.     

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.     

选择性血管结扎法建立大鼠脑动脉瘤模型

目的 探讨选择性血管结扎法对大鼠脑动脉瘤形成的影响.方法 SD大鼠50只,随机分为3组:(1)A组20只:结扎左侧颈总动脉+两侧肾动脉后支(各侧1支);(2)B组20只:"8"字形结扎左侧颈内、外动脉+电凝并切断两侧肾动脉(各侧只留1个分支);(3)C组为假手术组10只.术后喂养含0.9%的盐及0.12%β-氨基丙腈的饲料.4周后处死,取大鼠脑动脉Willis环,在光镜下观察其病理的变化.结果 A组大鼠ACA/OA分叉处均未见有进展期动脉瘤,仅3个早期动脉瘤样改变.B组大鼠中发现12个进展期动脉瘤和2个早期动脉瘤样改变.C组中未见动脉瘤形成.结论 血管壁结构的破坏或变弱和高血液动力学压力是动脉瘤形成的主要因素.     

Wall shear stress in intracranial aneurysms and adjacent arteries

Hemodynamic parameters play an important role in aneurysm formation and growth. However, it is difficult to directly observe a rapidly growing de novo aneurysm in a patient. To investigate possible associations between hemodynamic parameters and the formation and growth of intracranial aneurysms, the present study constructed a computational model of a case with an internal carotid artery aneurysm and an anterior communicating artery aneurysm, based on the CT angiography findings of a patient. To simulate the formation of the anterior communicating artery aneurysm and the growth of the internal carotid artery aneurysm, we then constructed a model that virtually removed the anterior communicating artery aneurysm, and a further two models that also progressively decreased the size of the internal carotid artery aneurysm. Computational simulations of the fluid dynamics of the four models were performed under pulsatile flow conditions, and wall shear stress was compared among the different models. In the three aneurysm growth models, increasing size of the aneurysm was associated with an increased area of low wall shear stress, a significant decrease in wall shear stress at the dome of the aneurysm, and a significant change in the wall shear stress of the parent artery. The wall shear stress of the anterior communicating artery remained low, and was significantly lower than the wall shear stress at the bifurcation of the internal carotid artery or the bifurcation of the middle cerebral artery. After formation of the anterior communicating artery aneurysm, the wall shear stress at the dome of the internal carotid artery aneurysm increased significantly, and the wall shear stress in the upstream arteries also changed significantly. These findings indicate that low wall shear stress may be associated with the initiation and growth of aneurysms, and that aneurysm formation and growth may influence hemodynamic parameters in the local and adjacent arteries.     

犬实验性动脉瘤血管内支架置入前后对照研究

目的探讨囊状动脉瘤行血管内支架治疗前后血流动力学、病理学变化与动脉瘤生长、血栓形成或破裂之间的相互关系.方法采用静脉移植法建立9只犬颈总动脉动脉瘤模型,1周后行彩色多普勒超声及DSA检查.5只犬于动脉瘤口成功置入支架,1个月后再行彩色多普勒超声、DSA及组织病理学检查.结果 DSA、彩色多普勒超声检测能显示动脉瘤位置、形态,并能检阅支架置入前后瘤体内及载瘤动脉内血液循环状态.置入支架组1个月后瘤腔完全闭塞,新生纤维样组织环绕支架金属丝表面.结论支架置入后改变了动脉瘤附近血流动力学,可促进瘤腔内血栓形成.     

iNOS在颅内囊性动脉瘤瘤壁中的表达及意义

目的探讨诱导性一氧化氮合酶（iNOs）在颅内囊性动脉瘤瘤壁中的表达及其意义。方法应用免疫组化染色和原位杂交染色技术检测iNOS在颅内囊性动脉瘤和正常动脉血管壁组织中的表达。结果所有脑动脉瘤标本中均可见iNOS表达，而正常脑动脉标本中则未见其表达：iNOS阳性表达部位主要在动脉瘤壁外膜和中膜的炎症浸润区的炎症细胞（如淋巴细胞、单核巨噬细胞）的胞浆内。结论动脉瘤的发生可能与局部iNOS过度表达，继而合成大量的NO有关。     

Elastic skeleton of intracranial cerebral aneurysms in rats

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.     

Effect of contralateral carotid ligation on experimental carotid artery aneurysm in the rat.

Haemodynamic factors in the formation and development of saccular aneurysms have been widely studied. Saccular aneurysms could appear and grow at the side of the increased blood flow. The effects of contralateral carotid ligation on the formation and growth of our experimental saccular aneurysms were studied. Measurement and pathological examination showed that the haemodynamic changes could facilitate the development of saccular aneurysms, but by itself could not bring about their formation.     

Identical cerebral aneurysms in siblings: report of two families.

Two pairs of sisters with identical cerebral aneurysms are reported. In the first family, a sibship of three, the two female members presented with subarachnoid haemorrhages from identical, left internal carotid artery bifurcation aneurysms. The subarachnoid haemorrhage occurred in one of the sisters at the age of 20 and at the age of 50 in the other. The remaining healthy sibling, a 40-year-old male, underwent elective cerebral angiography, which was normal. The other sibship, two 48-year-old female identical twins, had identical right middle cerebral artery aneurysms. The first twin became symptomatic after subarachnoid haemorrhage. The aneurysm in her identical twin was identified by screening angiography. There were no verified subarachnoid haemorrhages among the parents and grandparents in either family. No systemic anomalies were identified and collagen type 3 deficiencies were excluded. The identical location of these familial aneurysms, particularly in view of the relatively rare location in the first family, suggests that local factors in the developing vascular tree may play a role in the pathogenesis of saccular aneurysms in addition to systemic anomalies affecting the general structure of cerebral vascular walls.     

Development of 'De novo' Aneurysm after Therapeutic Carotid Occlusion

Carotid occlusion is an inevitable therapeutic modality for the treatment of complex aneurysms such as giant, traumatic, and intracavernous aneurysms. Late complications of carotid occlusion include ''de novo'' aneurysm formation at a distant site because of hemodynamic changes in the circle of Willis. We report a case of de novo aneurysm in a vessel that appeared to be normal on initial angiography. The patient developed an anterior communicating artery aneurysm and marked growth of a basilar bifurcation aneurysm 9 years after trapping of the left internal carotid artery for the treatment of a ruptured large saccular aneurysm involving ophthalmic and cavernous segments. We propose that patients who undergo therapeutic carotid occlusion should be periodically followed by magnetic resonance angiography or computed tomographic angiography to evaluate the possibility of de novo aneurysm formation; this advice is in line with previous reports.     

实验性肾性高血压大鼠脑动脉瘤模型的建立及发生机制探讨

目的 探讨高血压大鼠脑血管早期病理改变与脑微动脉瘤形成的关系。方法 建立肾性高血压大鼠模型,应用光镜及电镜观察脑血管组织学改变。结果 实验组发现2个肉眼可见的动脉瘤及10个镜下早期动脉瘤。动脉分叉部内膜垫的变化与动脉瘤的病理改变程度有密切关系,动脉瘤形成早期即有内皮细胞损伤。结论 持续高血压引起的内弹力膜与平滑肌的破坏导致了动脉瘤的发生。     

颅内典型囊性动脉瘤的三维数值模拟及血流动力学分析

目的应用计算流体力学软件进行三维数值模拟,分析不同类型动脉瘤的血液动力学特性。方法根据动脉瘤瘤体与载瘤动脉的关系,将颅内典型囊性动脉瘤分为A（动脉瘤位于血管弓背侧）、B（动脉瘤位于血管弓内侧）、C（分叉部动脉瘤,瘤轴平面与载瘤动脉轴共面）,D（分叉部动脉瘤,瘤轴平面与载瘤动脉轴不共面）四类。联合应用Matlab软件、Ansys软件、Fluent软件及自写程序对颅内囊性动脉瘤进行计算机数值模拟分析。结果颅内动脉瘤模型流入道的血流速度、动压及壁面切应力最高,流出道次之．顶部最低;A、B、D类动脉瘤冲击域壁面切应力最大;C类动脉瘤内动脉压普遍较高。结论对A、B、D类动脉瘤,冲击域壁面切应力最大可能是动脉瘤生长的主要因素,而其顶部壁面切应力不足可能是破裂的主要因素之一;对C类动脉瘤,动脉瘤内动压较高是其破裂的主要因素。     

Multiple aneurysms associated with bilateral carotid occlusion and venous angioma: surgical management risk-case report.

A unique case of multiple aneurysms associated with bilateral carotid artery occlusion and venous angioma is described. A 42 year old female presented with subarachnoid haemorrhage. Cerebral angiograms demonstrated(1) a ruptured saccular aneurysm in the right posterior cerebral artery,(2) bilateral occlusion of internal carotid arteries,(3) a rete mirabile in the subtemporal fossa fed by left external carotid artery which connected with the internal carotid artery at the cavernous portion where a saccular aneurysm had formed, and(4) a venous angioma in the posterior fossa. The ruptured aneurysm of the posterior cerebral artery was obliterated preserving the anterior choroidal arteries. However, a left hemiparesis developed and CT scan revealed a small low density area in the right posterior limb of the internal capsule postoperatively. A ruptured aneurysm associated with bilateral extracranial carotid occlusion poses a clinical dilemma and treatment of such cases is challenging and difficult. The non-surgical and surgical outcomes of ruptured cerebral aneurysms associated with internal carotid occlusion are reviewed.     

Early changes of experimentally induced cerebral aneurysms in rats: scanning electron microscopic study

To obtain information about the early changes of experimentally induced cerebral aneurysms in rats, the luminal surface of branching areas of their cerebral arteries was examined with a scanning electron microscope. At the branching sites of major cerebral arteries in the control animals, the intima just distal to the apex markedly protruded into the lumen forming a linear bank-like intimal pad. Along and distal to this pad, there was a shallow long groove (juxta-apical groove). Such grooves were much deeper and wider in experimental animals than those in the control rats. By studying various stages of early aneurysmal changes, cerebral aneurysms were proven to develop from such grooves. In deep juxta-apical grooves and small aneurysms, round regenerated endothelial cells with a large number of microvilli were diffusely present. Degenerated cells with balloons and craters were observed intermingled with such regenerated cells. Interendothelial gaps were also seen. The present study showed the complex structure of the apex of arterial bifurcation in rats, including bank-like intimal pads. Such complex structures of the branching sites were considered to be responsible for the initiation of cerebral aneurysms due to endothelial injury possibly caused by turbulent flow there.     

Immunomorphological aspects of formation of an intracranial aneurysm

An immunohistochemical study of the arteries of the circle of Willis and the walls of ampullar aneurysms indicated the impaired expression of the matrix proteins collagens I, III, and V in the aneurysms. Examination of the proliferative activity of cell elements in different parts of the aneurysmal sac showed a significant activation of proliferative processes along the cervical parts of aneurysms and the presence of proliferating cells in the body and fundus of aneurysms different in sizes. The findings suggest that the magnitude of proliferative and synthetic processes plays a definite role in the formation of an aneurysmal sac and in the so-called growth of aneurysms.