Frontiers in Neuroscience · Oct 30, 2026
Nights Without Darkness: Effects of Artificial Light-at-Night on Neurovascular and Glymphatic Function
By Lily G. Roth, Joseph A. Seggio
Urbanization has largely eliminated true darkness. Light-at-night disrupts circadian organization and has been linked to cardiovascular disease and cognitive decline. Two circadian-dependent brain systems have received little attention: the glymphatic system, which clears amyloid-β along perivascular channels during sleep, and the neurovascular unit, whose barrier integrity and perfusion vary diurnally. In rodents, nighttime light reduces hippocampal microvascular density, enlarges infarcts and increases mortality after cerebral ischemia, and is accompanied by amyloid accumulation and neuroinflammation. The worsening of ischemic injury appears to depend on the circadian disruptive potential of the light, because long-wavelength light leaves outcomes unchanged. Sleep was not measured in the ischemia experiments, so whether the effect is independent of sleep is unknown. Light may also influence the vasculature through retinal pathways that regulate the noradrenergic tone driving perivascular flow, although this remains untested. The effect may require intact local tissue clocks. Many common laboratory mouse strains synthesize little melatonin, yet inflammatory, amyloid, and ischemic responses to circadian disruption persist, suggesting these models may underestimate human vulnerability. In humans, night-shift work is associated with cerebrovascular disease and with a reduced diffusion-imaging index of glymphatic function, though light and sleep loss are confounded. No chronic dim light-at-night exposure has been paired with a direct measure of glymphatic transport. We argue that the vasculature is the best-characterized point at which light-at-night could affect both systems, because the vessels regulating perfusion also drive perivascular flow. Clearance also depends on non-vascular mechanisms, and this convergence has not been tested under light-at-night.