Researchers at the University of Rochester Medical Center have identified a potential new approach to improving stroke recovery, finding that strengthening the body’s natural circadian rhythms helped reduce inflammation, improve brain function and speed recovery in laboratory mice after stroke.
The study, led by University of Rochester Medicine neuroscientist Lauren Hablitz and published in the Journal of Clinical Investigation, suggests that the body’s internal clock may play a much larger role in healing after brain injury than previously understood. Researchers say the findings could eventually lead to new therapies that remain effective long after the narrow treatment window for emergency stroke interventions has passed.
The research centers on the brain’s glymphatic system, a network discovered by University of Rochester Medicine scientist Dr. Maiken Nedergaard and colleagues in 2012. The system circulates cerebrospinal fluid through the brain, helping remove waste products, inflammatory molecules and other debris. Previous studies have shown the glymphatic system functions most effectively during sleep and plays a critical role in maintaining brain health.
Hablitz and her team focused on the connection between the glymphatic system and circadian rhythms, the body’s internal 24-hour clock. Researchers noted that stroke patients frequently experience disrupted sleep-wake cycles after injury, and those disruptions are often associated with poorer recovery outcomes, depression and reduced quality of life.
To test whether reinforcing the body’s natural rhythms could improve recovery, researchers evaluated several interventions known to influence circadian function, including timed light exposure, melatonin, time-restricted feeding and a clock-targeting drug known as KL001. After first demonstrating that the approaches improved glymphatic function in healthy animals, researchers tested the most promising options in mouse models of stroke.
The results were significant. Even when treatment did not begin until three days after a stroke—well beyond the window when clot-busting drugs are typically effective—mice receiving the interventions experienced improved motor recovery, smaller areas of brain damage, better glymphatic function and lower levels of inflammatory molecules in the brain.
Researchers believe the findings point to a different way of thinking about post-stroke inflammation. Rather than targeting individual inflammatory pathways, the team suspects improving the brain’s ability to clear harmful molecules may be equally important.
The most immediately practical finding involved time-restricted feeding, a behavioral intervention already being studied for conditions including obesity, diabetes and cardiovascular disease. Because it does not rely on new medical devices or invasive procedures, researchers said it could potentially be implemented both in hospitals and at home if future studies show similar benefits in humans.
The researchers cautioned that the findings are currently limited to animal models and that additional studies will be needed before human clinical trials can be considered. Future research will focus on determining whether improved glymphatic function directly drives recovery and whether circadian-based therapies can be safely translated into patient care.
More broadly, the study adds to a growing body of evidence suggesting sleep, circadian rhythms and the brain’s waste-clearing systems play a central role in neurological health. Researchers believe a better understanding of those connections could ultimately lead to new treatments not only for stroke patients, but also for other neurological disorders linked to inflammation and impaired waste clearance.
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