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

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.

胶质淋巴系统（glymphatic system）的核心功能是清除大脑内潜在有害的代谢物与蛋白质。本研究借助动态对比增强磁共振成像（dynamic contrast-enhanced magnetic resonance imaging）技术，对完全清醒的大鼠开展扫描，追踪随明暗周期同步的脑脊液清除进程，并分析该进程与特定脑区的睡眠-觉醒周期、脑血流量及脑温度之间的关联。参与昼夜节律计时与睡眠-觉醒节律调控的脑区，在大鼠处于光照期（即静息与睡眠时段）时，表现出较高的对比剂清除率或较低的对比剂蓄积水平。全脑的清除过程呈现显著异质性：大脑背侧区域的清除率最低，中脑/脑桥与大脑腹侧表面的清除率最高。这种清除率的异质性分布，与已有文献报道的清醒动物脑温度梯度变化及区域差异特征高度吻合。本研究采用三维定量超短回波时间对比增强成像（3D Quantitative Ultra-Short Time-to-Echo Contrast Enhanced imaging）技术，对大鼠脑内的小、中、大动静脉进行三维重建，结果显示清除率最高的脑区与该大血管系统存在明显重叠。本研究围绕明暗周期、脑温度及脑血流量对胶质淋巴系统功能的影响，提出了全新的研究问题与理论思考方向。