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.

类淋巴系统（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。本研究采用动态对比增强磁共振成像（dynamic contrast-enhanced magnetic resonance imaging）技术，对完全清醒状态下的大鼠进行成像，追踪随明暗周期节律同步的脑内清除过程，并分析其与特定脑区的睡眠-觉醒周期、脑血流量及脑温度的关联。结果显示，参与昼夜节律调控与睡眠-觉醒节律的脑区，在大鼠处于光照期（即静息与睡眠时段）时，表现出更高的对比剂清除率或更低的对比剂蓄积量。全脑的清除活动呈现异质性：大脑背侧区域的清除率最低，而中脑/脑桥及大脑腹侧表面的清除率最高。这种清除率的异质性分布，与已发表文献中清醒动物脑温度的梯度变化及区域差异相一致。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，重建了大鼠脑内的小、中、大动静脉血管，并发现清除率最高的脑区与该大血管网络存在重叠。本研究为探究明暗周期、脑温度及脑血流量对类淋巴系统功能的影响提出了新的问题与理论思考方向。