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

Published: 14 October 2019| Version 1 | DOI: 10.17632/2nmnjx66w7.1


The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced magnetic resonance imaging was used in fully awake rats to follow clearance entrained to the light-dark cycle and its 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 high clearance or low accumulation of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain clearance was heterogeneous. Clearance was lowest along the dorsal cerebrum and highest in the midbrain/pons and along the ventral surface of the brain. This heterogenous distribution of clearance paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. 3D Quantitative Ultra-Short 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 highest clearance overlapped with this macrovasculature. This study raises new questions and theoretical considerations on the impact of the light-dark cycle, brain temperature and blood flow on the function of the glymphatic system.


Steps to reproduce

There are two folders, one for Dark cycle (Dark) and one for light Cycle (Light). Dark cycle has data acquired from 6 rats and light cycle has 7 rats. Each folder has NifTi (nii) files for each time point. The spredsheet in the root folder indicates file name and time point data is collected. The Publication submitted to PNAS describes Data analysis and Results. Slope_RG: T1-weighted image data were rescaled to the original intensity measurements (divided by the receiver gain and multiplied by the scaling factor called SLOPE) for each time point for each subject using this sheet. Timeinfo: This file shows data collected at each time point and respective nii file identifier. The last number in nii filename is image data point in excel sheet.


Northeastern University


Circadian Rhythm, Cerebrospinal Fluid, Neurodegenerative Process, Substantia nigra, Preclinical Study