Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats
Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats
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DOI：
10.3171/jns-07/08/0405
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发表时间：
2007-08-01
影响因子：
4.1
通讯作者：
Satoh, Koichi
中科院分区：
文献类型：
--
作者：
Jamous, Mohammad A.;Nagahiro, Shinji;Satoh, Koichi
目的。颅内动脉瘤是蛛网膜下腔出血的主要原因，其发病率和死亡率较高。尽管颅内动脉瘤的显微外科和血管内治疗取得了进展，但人们对其起源、生长和破裂的机制知之甚少。为了阐明导致颅内动脉瘤形成的一系列早期事件，作者将血管腐蚀铸件上的动脉瘤形态变化与大鼠脑动脉中的平行病理变化进行了比较。方法。作者通过肾性高血压和结扎右颈总动脉在 40 只雄性 Sprague-Dawley 大鼠中诱发脑动脉瘤； 10只完整大鼠作为对照。使用Batson塑料试剂血管腐蚀铸件对大脑前动脉-嗅动脉分叉处进行形态学评估，并使用抗内皮一氧化氮合酶、α-平滑肌肌动蛋白、巨噬细胞和基质金属蛋白酶-9的抗体进行免疫组织化学评估。结果。手术治疗的大鼠表现出不同程度的动脉瘤变化。基于这些阶段性变化，作者提出颅内动脉瘤的形成始于心尖内膜垫的内皮损伤（第一阶段）；这导致炎症区域的形成（第二阶段），随后炎症区域部分撕裂或缺损。该缺陷的扩张形成颅内动脉瘤的病灶（第三期）。结论。这是第一项证明颅内动脉瘤形成的体内机制的研究。内皮损伤后的炎症反应是这些病变发病机制的基本步骤。在这项研究中，研究人员扩大了对颅内动脉瘤起源的认识，并为预防和治疗动脉瘤的措施的进一步发展做出了贡献。
Object. Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats.Methods. The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9.Results. Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III).Conclusions. This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.