Mechanism of cerebral aneurysm formation in experimental model rats

实验模型大鼠脑动脉瘤形成机制

• 批准号: 17390401
• 负责人: NAGAHIRO Shinji
• 金额: $ 8.64万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390401/
• 关键词: cerebral aneurysm; pathogenesis; experimental model; estrogen; hypertension; female

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).

根据流行病学数据显示绝经后妇女脑动脉瘤(CA)的高发病率，我们建立了一种可重复性的雌性大鼠脑动脉瘤模型。为了确定导致实验性脑动脉瘤(CA)形成的早期超微结构改变，我们诱导了肾性高血压和右侧颈总动脉结扎。为了进一步阐明荷尔蒙的作用，我们研究了卵巢切除术的效果。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，提示激素在脑动脉瘤的发病机制中起一定作用。(美国神经外科杂志)2005；103：1046-51)(神经外科杂志。2005；103：1052-7)为了阐明导致IA形成的一系列早期事件，我们比较了脑动脉中动脉瘤性血管腐蚀的形态变化及其平行的病理变化。我们认为IAS的形成始于顶端内膜垫的内皮损伤(阶段I)，这导致炎症区的形成(阶段II)。炎症区的部分撕裂或缺陷将随之而来。这一缺陷的扩展形成了IA的病灶(III期)。我们的实验首次证实了在体内导致囊状IAS形成的超微结构、形态和病理变化序列。关于这些变化的详细知识对于理解IA的发病机制以及引入新的预防和治疗策略以中断这种一连串的动脉瘤变化至关重要(J NeuroSurg。2007年，在印刷中)。

项目成果

Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I: experimental study of the effect of oophorectomy in rats

• DOI: 10.3171/jns.2005.103.6.1046
• 发表时间: 2005-12-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Jamous, MA;Nagahiro, S;Satoh, K
• 通讯作者: Satoh, K

Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats

• DOI: 10.3171/jns.2005.103.6.1052
• 发表时间: 2005-12-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Jamous, MA;Nagahiro, S;Satoh, K
• 通讯作者: Satoh, K

Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats

• DOI: 10.3171/jns.2005.102.3.0532
• 发表时间: 2005-03-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Jamous, MA;Nagahiro, S;Satomi, J
• 通讯作者: Satomi, J