Circadian rhythms in ischemic stroke: From pathogenesis to chronotherapy

Abstract

Circadian rhythms significantly influence the onset, development, and outcome of ischemic stroke, with the biological clock likely playing a key role in its pathophysiology. In this review, we provide a systematic summary of the influence of circadian rhythms on stroke risk factors, including blood pressure, glucose metabolism, lipid homeostasis, and atrial fibrillation, and further explore their impact across different stages of recovery post-stroke. These encompass metabolic alterations in the ischemic penumbra during the hyperacute phase, excitotoxicity, oxidative stress, and neuroinflammation in the acute phase, as well as glial scar formation and neural remodeling during the subacute and chronic recovery phases. Building on this mechanistic foundation, we assess the role of chronobiology in stroke interventions, including thrombolysis, thrombectomy, neuroprotective strategies, and rehabilitation training. We also discuss key challenges in the field, such as barriers to translating preclinical findings to clinical applications, limitations in circadian rhythm assessment, and practical challenges in implementing circadian-based interventions. Ultimately, this review aims to evaluate the potential of chronotherapy in ischemic stroke and to advance the development of personalized, precision medicine approaches.