Despite advances in clinical diagnosis and increasing numbers of patients eligible for revascularisation, ischaemic stroke remains a significant public health concern accounting for 3.3 million deaths annually. In addition to recanalisation therapy, patient outcomes could be improved through cerebroprotection, but all translational attempts have remained unsuccessful. In this narrative review, we discuss potential reasons for those failures. We then outline the diverse, multicellular effects of ischaemic stroke and the complex temporal sequences of the pathophysiological cascade during and following ischaemia, reperfusion, and recovery. This evidence is linked with findings from prior cerebroprotective trials and interpreted for the modern endovascular era. Future cerebroprotective agents that are multimodal and multicellular, promoting cellular and metabolic health to different targets at time points that are most responsive to treatment, might prove more successful.
- clinical neurology
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Contributors AMS: Drafting/revision of the manuscript for content; Major role in the study concept or design. RWR: Drafting/revision of the manuscript for content. AAD: Drafting/revision of the manuscript for content. ABP: Drafting/revision of the manuscript for content. JAH: Drafting/revision of the manuscript for content; Major role in the study concept or design. AB: Drafting/revision of the manuscript for content; Major role in the study concept or design.
Funding AB is funded by grants from the Leducq Foundation and the Albert Einstein. Society. JAH is funded by grants from the Neiman Health Policy Institute.
Competing interests AB is senior medical science advisor and co-founder of Brainomix, a company that develops electronic ASPECTS (e-ASPECTS). JAH is a consultant for Medtronic, Persica, and Spine Biopharma, chair for DSMB Balt, and is deputy editor at JNIS. ABP is Consultant for Penumbra, MicroVention, and Medtronic. The other authors do not declare any conflicts of interest.
Provenance and peer review Not commissioned; externally peer reviewed.