Grüter Basil E, von Faber-Castell Fabio, Marbacher Serge
Department of Neurosurgery, 30231Kantonsspital Aarau, Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
J Cereb Blood Flow Metab. 2022 Sep;42(9):1568-1578. doi: 10.1177/0271678X211057498. Epub 2021 Nov 19.
The development of new treatment strategies for intracranial aneurysms (IAs) has been and continues to be a major interest in neurovascular research. Initial treatment concepts were mainly based on a physical-mechanistic disease understanding for IA occlusion (lumen-oriented therapies). However, a growing body of literature indicates the important role of aneurysm wall biology (wall-oriented therapies) for complete IA obliteration. This systematic literature review identified studies that explored endovascular treatment strategies for aneurysm treatment in a preclinical setting. Of 5278 publications screened, 641 studies were included, categorized, and screened for eventual translation in a clinical trial. Lumen-oriented strategies included (1) enhanced intraluminal thrombus organization, (2) enhanced intraluminal packing, (3) bridging of the intraluminal space, and (4) other, alternative concepts. Wall-oriented strategies included (1) stimulation of proliferative response, (2) prevention of aneurysm wall cell injury, (3) inhibition of inflammation and oxidative stress, and (4) inhibition of extracellular matrix degradation. Overall, lumen-oriented strategies numerically still dominate over wall-oriented strategies. Among the plethora of suggested preclinical treatment strategies, only a small minority were translated into clinically applicable concepts (36 of 400 lumen-oriented and 6 of 241 wall-oriented). This systematic review provides a comprehensive overview that may provide a starting point for the development of new treatment strategies.
颅内动脉瘤(IA)新治疗策略的开发一直是且仍然是神经血管研究的主要关注点。最初的治疗理念主要基于对IA闭塞的物理 - 机械性疾病理解(以管腔为导向的疗法)。然而,越来越多的文献表明动脉瘤壁生物学(以壁为导向的疗法)在IA完全闭塞中的重要作用。本系统文献综述确定了在临床前环境中探索动脉瘤治疗血管内治疗策略的研究。在筛选的5278篇出版物中,纳入了641项研究,进行分类并筛选最终是否可转化为临床试验。以管腔为导向的策略包括:(1)增强管腔内血栓形成,(2)增强管腔内填塞,(3)管腔内间隙桥接,以及(4)其他替代概念。以壁为导向的策略包括:(1)刺激增殖反应,(2)预防动脉瘤壁细胞损伤,(3)抑制炎症和氧化应激,以及(4)抑制细胞外基质降解。总体而言,以数量计,以管腔为导向的策略仍然比以壁为导向的策略占主导地位。在众多建议的临床前治疗策略中,只有一小部分转化为临床适用的概念(400项以管腔为导向的策略中有36项,241项以壁为导向的策略中有6项)。本系统综述提供了全面的概述,可为新治疗策略的开发提供起点。