Department of Neurosurgery University Hospital Aachen, RWTH Aachen University Aachen Germany.
Translational Neurosurgery and Neurobiology, Department of Neurosurgery University Hospital Aachen, RWTH Aachen University Aachen Germany.
J Am Heart Assoc. 2024 Mar 5;13(5):e032694. doi: 10.1161/JAHA.123.032694. Epub 2024 Feb 29.
Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models.
We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used.
Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential.
URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.
迟发性脑缺血是蛛网膜下腔出血后死亡和残疾的重要原因。尽管临床前模型显示出了有希望的结果，但临床试验始终未能复制治疗策略的成功。缺乏标准化的实验设置和结果评估，特别是关于继发性血管痉挛/缺血事件，可能是转化失败的部分原因。本研究旨在描述最近的大鼠和小鼠蛛网膜下腔出血模型中继发性血管痉挛和缺血事件的程序特征和评估方式，作为与临床相关的迟发性脑缺血的替代指标。
我们使用迟发性脑缺血/血管痉挛作为结果参数，对 2016 年至 2020 年发表的大鼠和小鼠体内蛛网膜下腔出血研究进行了系统回顾。我们的分析包括 102 项合格的研究。在小鼠研究（n=30）中，主要使用血管内穿孔模型，而大鼠研究主要采用脑室内血注射来模拟蛛网膜下腔出血。特别是，注射模型在注射体积、速度和脑脊液抽取方面存在很大差异。所有模型都普遍缺乏围手术期监测，体温和血压是记录最频繁的参数（分别为 62%和 34%）。血管痉挛事件主要通过大脑大动脉的显微镜检查来评估。在 90%的大鼠和 86%的小鼠研究中，仅使用雄性动物。
本研究强调了实验性蛛网膜下腔出血研究中程序特征和结果评估的显著异质性。为了解决这些挑战，起草标准化指南以及确保资助者和期刊严格控制方法学和实验质量是至关重要的。
网址：https://www.crd.york.ac.uk/prospero/；唯一标识符：CRD42022337279。
