背景:已提出将氩气(Ar)作为多种临床条件下的潜在治疗剂,特别是在器官保护方面。然而,临床前模型的数据相互矛盾,再加上Ar给药方案和结果评估的巨大差异,已被报道。这项研究的目的是回顾关于Ar治疗的证据,对其神经保护作用进行了广泛的研究,并总结所有测试的给药方案。
方法:使用PubMed数据库,系统审查了所有关于Ar治疗的现有临床前和临床研究(注册:https://doi.org/10.17605/OSF.IO/7983D)。筛选研究标题和摘要,全文回顾后,从相关研究中提取数据。排除标准包括缺乏全文和非英语语言。此外,还进行了荟萃分析,以评估Ar在不同临床条件下作为神经保护剂的潜力:心脏骤停,创伤性脑损伤,缺血性卒中,围产期缺氧缺血性脑病,蛛网膜下腔出血。神经系统的标准化平均差异,认知和运动,组织学,并对生理指标进行了评估,通过适当的测试,临床,和实验室变量。使用系统审查中心实验动物实验工具评估体内研究的偏倚风险,而体外研究使用健康评估和翻译办公室开发的工具进行评估。
结果:系统评价检测到60项实验研究(16项体外,7离体,31在体内,6在体外和体内)研究Ar的作用。仅发现一项临床研究。来自6项体外研究和19项体内研究的数据被纳入荟萃分析。在临床前模型中,Ar给药导致神经系统改善,认知和运动,和组织学结果,而生理参数没有任何变化(即,无不良事件)。
结论:基于实验研究的系统综述和荟萃分析支持Ar的神经保护作用,从而为Ar治疗在人类中的潜在翻译提供了理论基础。尽管遵守既定的准则和方法,数据可用性的局限性阻碍了进一步分析以调查由于研究设计导致的异质性的潜在来源.
背景:这项研究部分由意大利卫生部资助-当前研究IRCCS和意大利MinisterodellaSaluteItaliano,RicercaFinalizzata,项目编号.RF2019-12371416。
BACKGROUND: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to
review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols.
METHODS: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text
review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic
Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation.
RESULTS: The systematic
review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events).
CONCLUSIONS: This systematic
review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design.
BACKGROUND: This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.