INTRODUCTION: Circadian rhythm disruption (CRD) is a major driver of immune dysregulation; however, whether CRD promotes ischemic stroke (IS) progression through immune imbalance and the underlying molecular mechanisms remain unclear. METHODS: Transcriptomic data from human IS brain tissues were analyzed to identify CRD associated regulators using machine-learning approaches. A CRD score model was constructed to quantify circadian disruption. Circadian timing-dependent stroke models were established to evaluate diurnal variation in stroke severity and gene rhythmicity in vivo. Single-cell transcriptomic analysis of peripheral blood mononuclear cell -derived scRNA-seq data was performed to characterize CRD-associated immune remodeling. Virtual gene knockdown analysis using the scTenifoldKnk framework, together with experimental validation including microglial gene silencing and T cell co-culture in vitro, as well as adeno-associated virus (AAV)-mediated gene intervention in a transient middle cerebral artery occlusion (tMCAO) model in vivo, were conducted to assess immunoregulatory effects and neurological recovery. RESULTS: T-cell infiltration and inflammatory signaling, enhanced Claudin-5 expression, improved neurological function, and promoted post-stroke recovery. CONCLUSION: This study indicates that CORO1C acts as a pivotal regulator that mediates circadian rhythm disruption-driven immune dysregulation, thereby influencing stroke progression and neurological recovery.
Yan et al. (Fri,) studied this question.