Cytoprotection Concepts for Ischemic Stroke in the Recanalization Era

Recanalization therapies for ischemic stroke, in particular endovascular thrombectomy, have revolutionized acute stroke management. Cytoprotective approaches were unsuccessfully tested in the pre-recanalization era but have seen a renaissance in translational research and early clinical trials as a potential intervention to augment the impact of recanalization therapies. The new clinical trial approaches in which cytoprotective therapies are now being applied require refinement of cytoprotective application strategies. This has a profound impact on both preclinical translational and clinical research. This review summarizes current cytoprotection concepts and explains their rationale based on ischemic stroke pathophysiology and provides an overview of cytoprotection approaches currently under clinical assessment. Preclinical assessment of novel cytoprotective paradigms will require advanced in vivo testing in models resembling human stroke patients as much as possible. The review therefore also describes ways to improve preclinical and translational research with respect to comorbidities and other aspects impacting stroke pathophysiology. Moreover, the role of modern brain imaging approaches is discussed including their use as potential biomarkers or patient selection tools. The review further provides detailed considerations of novel clinical trial design features for cytoprotection trials in the context of recanalization therapies and provides an outlook on potential future research approaches.