New Delhi: Improving sleep by reinforcing the body’s natural daily rhythms could help the brain recover after a stroke, potentially providing a new strategy to enhance the brain’s waste clearance and outcomes, according to a new study.
The findings, published in the Journal of Clinical Investigation, show that interventions designed to reinforce the body’s natural circadian rhythms, such as timed light exposure, melatonin or a body clock-targeting drug, improved recovery in mouse models of stroke.
Researchers from the University of Rochester Medical Center also found improvements in the glymphatic system — the brain’s waste-clearing network — and reduced levels of inflammatory molecules that can linger in the brain after a stroke.
The system moves cerebrospinal fluid along blood vessels and through brain tissue, delivering nutrients and helping remove waste products and inflammatory signals.
“The discussion of stroke recovery really starts with the idea that stroke is not just a vascular event, but also a disorder of timing,” lead author Lauren Hablitz, a neuroscientist at the University of Rochester Medical Center, said.
Strokes are considered to follow predictable time-of-day patterns, with their likelihood of occurring being higher in the morning. They can also be often more severe near the end of the sleep period.
At the same time, many stroke patients experience disrupted sleep-wake cycles after their injury, and those disruptions are associated with poorer recovery, depression, and lower quality of life, the researchers said.
“That led us to ask a simple question. If timing is broken after a stroke, can we improve recovery by reinforcing the biological clock?” Hablitz said.
The researchers added that previous studies show an impaired glymphatic function after stroke, potentially limiting the brain’s ability to clear harmful molecules that accumulate during recovery.
The team evaluated interventions known to influence the body’s internal clock, including timed light exposure, melatonin, a clock-targeting drug called ‘KL001’, and time-restricted feeding — each could enhance glymphatic function in healthy animals.
The “most promising” approaches — KL001 and time-restricted feeding — were then tested in mouse models of stroke.
Treatment began three days after stroke, well beyond the narrow treatment window for clot-busting drugs and other acute interventions, the researchers said.
However, despite the delay, the animals receiving an intervention showed an improved motor recovery, smaller lesion volumes, enhanced glymphatic flow, and lower levels of inflammatory cytokines in the brain.
“All of the cytokines moved in the same direction. That suggests we may not be targeting one specific inflammatory pathway. Instead, we may be helping the brain clear inflammatory signals more effectively,” Hablitz said.
The findings could have practical implications for stroke rehabilitation as the most promising intervention involved time-restricted feeding — a behavioral approach already being studied for obesity, diabetes, cardiovascular disease, among others, the team said.
They added that the findings are currently limited to animal models and that more work is needed to understand exactly how circadian rhythms, glymphatic function, and inflammation interact after stroke.
Further, the study reflects a growing shift in neuroscience that views sleep, circadian rhythms, and fluid transport as fundamental drivers of brain health, the researchers said.
