Miyata Haruka, Imai Hirohiko, Koseki Hirokazu, Shimizu Kampei, Abekura Yu, Oka Mieko, Kawamata Takakazu, Matsuda Tetsuya, Nozaki Kazuhiko, Narumiya Shuh, Aoki Tomohiro
1Department of Molecular Pharmacology, Research Institute, and.
2Core Research for Evolutional Science and Technology (CREST) from the Japanese Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka.
J Neurosurg. 2019 Aug 16;133(3):789-799. doi: 10.3171/2019.5.JNS19405. Print 2020 Sep 1.
Subarachnoid hemorrhage (SAH) has a poor outcome despite modern advancements in medical care. The development of a novel therapeutic strategy to prevent rupture of intracranial aneurysms (IAs) or a novel diagnostic marker to predict rupture-prone lesions is thus mandatory. Therefore, in the present study, the authors established a rat model in which IAs spontaneously rupture and examined this model to clarify histopathological features associated with rupture of lesions.
Female Sprague Dawley rats were subjected to bilateral ovariectomy; the ligation of the left common carotid, the right external carotid, and the right pterygopalatine arteries; induced systemic hypertension; and the administration of a lysyl oxidase inhibitor.
Aneurysmal SAH occurred in one-third of manipulated animals and the locations of ruptured IAs were exclusively at a posterior or anterior communicating artery (PCoA/ACoA). Histopathological examination using ruptured IAs, rupture-prone IAs induced at a PCoA or ACoA, and IAs induced at an anterior cerebral artery-olfactory artery bifurcation that never ruptured revealed the formation of vasa vasorum as an event associated with rupture of IAs.
The authors propose the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs. Findings from this study provide important insights about the pathogenesis of IAs.
尽管现代医疗有所进步，但蛛网膜下腔出血（SAH）的预后仍较差。因此，必须开发一种预防颅内动脉瘤（IA）破裂的新型治疗策略或一种预测易破裂病变的新型诊断标志物。为此，在本研究中，作者建立了IA自发破裂的大鼠模型，并对该模型进行研究以阐明与病变破裂相关的组织病理学特征。
对雌性Sprague Dawley大鼠进行双侧卵巢切除术；结扎左颈总动脉、右颈外动脉和右翼腭动脉；诱导全身性高血压；并给予赖氨酰氧化酶抑制剂。
三分之一的手术动物发生了动脉瘤性SAH，破裂IA的位置仅位于后交通动脉或前交通动脉（PCoA/ACoA）。对破裂的IA、在PCoA或ACoA处诱导产生的易破裂IA以及在前脑动脉-嗅动脉分叉处诱导产生的从未破裂的IA进行组织病理学检查，结果显示血管滋养管的形成是与IA破裂相关的事件。
作者提出外膜结构变化即血管滋养管形成对IA破裂有影响。本研究结果为IA的发病机制提供了重要见解。
