Mechanism of cerebral aneurysm formation in experimental model rats

基于绝经后妇女脑动脉瘤（CA）发病率高的流行病学资料，我们建立了一个可重复的雌性大鼠CA模型。为了确定导致实验性脑动脉瘤（CA）形成的早期超微结构形态学变化，我们诱导了肾性高血压和右侧颈总动脉结扎。为了进一步阐明激素的作用，我们研究了卵巢切除术的影响。卵巢切除增加了大鼠对动脉瘤形成的易感性，激素替代治疗降低了CA的发生率，表明激素在脑动脉瘤的发病机制中起作用。（J Neurosurg. 2005 ; 103：1046-51）（J Neurosurg.二○ ○五年;一百零三：1052-7）为了阐明导致IA形成的一系列早期事件，将血管腐蚀铸型上的网状形态学变化与脑动脉中的平行病理变化进行了比较。我们认为IA的形成始于顶端内膜垫的内皮损伤（I期），这导致炎症区的形成（II期）。炎症区会出现部分撕裂或缺损。该缺损的扩大形成IA的病灶（III期）。我们的研究首次证明了导致囊状IA形成的超微结构形态学和病理学变化的序列。关于这些变化的详细知识对于理解IA发病机制以及引入中断这种级联的神经系统变化的新的预防和治疗策略是至关重要的（J Neurosurg. 2007，in press）.

Based on epidemiological data indicative of a high incidence of cerebral aneurysm (CA) in postmenopausal women, we established a reproducible CA model in female rats. To identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysm (CA), we induced renal hypertension and right common carotid artery ligation. To further elucidate the role of hormones, we examined the effects of oophorectomy.. The oophorectomy increased the susceptibility of rats to aneurysm formation and the incidence of CA was reduced by hormone replacement therapy, indicating that hormones play a role in the pathogenesis of cerebral aneurysms. (J Neurosurg. 2005 ; 103 : 1046-51) (J Neurosurg. 2005 ; 103 : 1052-7)To clarify the series of early events that leads to IA formation, the aneurysmal morphological changes on vascular corrosion cast to its parallel pathological changes in cerebral arteries were compared. We proposed that the formation of IAs starts with endothelial injury at the apical intimal pad (stage I), this lead to the formation of inflammatory zone (stage II). Partial tear or defect in the inflammatory zone will follow. Expansion of this defect forms the nidus for IA (stage III). Ours is the first demonstratation of the sequence of ultrastructural morphological and pathological changes that leads to the formation of saccular IAs in vivo. Detailed knowledge regarding these changes is crucial for an understanding of IA pathogenesis, and for introducing new preventive and therapeutic strategies that interrupt this cascade of aneurysmal changes (J Neurosurg. 2007, in press).