Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

Abstract

The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced MRI was used in fully awake rats to follow the redistribution of intraventricular contrast agent entrained to the light–dark cycle and its hypothetical relationship to the sleep–waking cycle, blood flow, and brain temperature in specific brain areas. Brain areas involved in circadian timing and sleep–wake rhythms showed the lowest redistribution of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain redistribution of contrast agent was heterogeneous. The redistribution was highest along the dorsal cerebrum and lowest in the midbrain/pons and along the ventral surface of the brain. This heterogeneous redistribution of contrast agent paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. Three-dimensional quantitative ultrashort time-to-echo contrast-enhanced imaging was used to reconstruct small, medium, and large arteries and veins in the rat brain and revealed areas of lowest redistribution overlapped with this macrovasculature. This study raises new questions and theoretical considerations of the impact of the light–dark cycle, brain temperature, and blood flow on the function of the glymphatic system.