Cerebral Blood Volume Modulates Glymphatic Influx Through Extra-ventricular Cerebrospinal Fluid Volume

The glymphatic system facilitates waste removal via cerebrospinal fluid (CSF) influx alongside perivascular spaces throughout the brain. Vasomotion, the slow motion of blood vessel (0.1-0.3 Hz), has been found to be one of the driving forces for perivascular clearance, but it is not clear whether more chronical change of vessel diameter, as reflected by macroscopic cerebral blood volume (CBV), has any impact on glymphatic function. Combining multimodal mouse MRI techniques, we investigated the relationship among glymphatic influx, CBV, CSF volume and EEG power under six different conditions (awake, dexmedetomidine, isoflurane, isoflurane/dexmedetomidine, ketamine/xylazine and awake with caffeine). We found dexmedetomidine and caffeine enhanced glymphatic influx, while isoflurane reduced it compared with awake condition. Quantitative CBV imaging revealed that glymphatic influx was negatively correlated to CBV across the above conditions. Furthermore, such negative correlation was found to be mediated in part by changes of extra-ventricular CSF volume, which was quantified using T1 MRI. Taken together, our results suggest that CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume. This new finding opens potential avenues to enhance brain waste clearance by regulating CBV, which could be beneficial for protein deposition related neurological diseases.