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Participants received daily oral semaglutide (up to 14 mg) or placebo for 104 weeks

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Glucocorticoids perform dual chrono-regulatory functions: entraining circadian oscillations in cytokine production (129132), and exerting phase-dependent immunosuppression through inhibition of pro-inflammatory transcription factors (including NF-B) (133136).Preserved circadian cortisol rhythmicity following stroke acts as an endogenous brake on neuroinflammation, thereby limiting persistent BBB dysfunction (137).Clinical investigations demonstrate that blunted circadian cortisol rhythmicity (non-dipping pattern) shows significant positive correlation with both the extent and progression of post-stroke BBB pathology (138).These findings suggest that targeting clock genes to optimize the timing of neuroendocrine factor release (e.g., aligning glucocorticoid peaks with ischemic injury cycles) may provide a strategy for BBB stabilization