Biomarkers of remote ischaemic conditioning in stroke and cerebral small vessel disease: a narrative review

Introduction: Remote ischaemic conditioning (RIC) is a promising treatment for neurological disorders. It involves cycles of temporary ischaemic stimulus, usually applied to a limb, and has shown significant improvement in neurological function in many trials. This review focuses on identifying and summarising the biomarkers of RIC that can enhance clinical practice and understanding of its mechanisms. Methods: A search was conducted in MEDLINE and EMBASE up to August 2025 using terms related to ischaemic conditioning. Studies were included if they were RCTs involving cerebrovascular disease, used RIC as treatment, and measured mechanistic biomarkers. We extracted and summarised data on study design, participant characteristics, RIC intervention protocols (including timing, frequency, duration, and pressure), biomarker types and measurement methods, timing of biomarker assessment, and main findings relating biomarker changes to clinical outcomes. Results: The review identified twenty-one RCTs examining biomarkers, including serum biomarkers, imaging markers, and other physiological indicators. Key biomarkers identified include systemic inflammatory cytokines and various imaging markers such as cerebral blood flow (CBF), white matter hyperintensities (WMH), and brachial artery flow-mediated dilation (BA-FMD). Conclusions: The evidence suggests that RIC modulates various biomarkers linked to neuroprotection and recovery. Reliable biomarkers of RIC would enhance the understanding of its mechanisms and improve targeted therapies. The clinical utility of these biomarkers requires further validation through large-scale trials. Standardised protocols and longitudinal studies are essential for optimising RIC therapy and improving patient outcomes in stroke and cerebral small vessel disease. Future research should focus on expanding our understanding of these biomarkers and their interactions with RIC, leading to more personalised and effective treatments.