International Business Department           Liu Bojia           May 20, 2023

  Sleep is undoubtedly an act necessary for human survival, and in the absence of sleep, individuals are susceptible to all types of negative effects, as studies published in Cell in 2023 have found that sleep deprivation conditions promote the accumulation of reactive oxygen species and lead to a severe storm of inflammatory factors. Other articles have noted that sleep deprivation accelerates age-aging brain physiology and leads to memory loss.

  In addition, the field of sleep research also has a kind of lymphatic system cleansing hypothesis has attracted much attention in recent years, which refers to the fact that after entering sleep, lymphatic fluid rushes into the brain, and then the toxic substances accumulated during the day along with out, as if the brain has completed the cleansing work in general.

  However, Professor Nicholas P. Franks' team at Imperial College London has a different view on this, he and his colleagues believe that there are still many controversial issues in the process of lymphoid cleansing, including the anatomical pathways of the brain involved in cleansing, the cleansing mechanism, and some research suggests that sleep can increase the overall flow of lymphoid fluid to enhance the efficiency of the cleansing, while other studies have found the opposite.

  To further confirm the relationship between sleep and toxic cleansing, in a recent paper published in Nature Neuroscience, they directly measured fluid flow and clearance efficiency in the brains of mice during waking, sleep or anaesthesia, and found that mice instead became less efficient at waste removal and moved less fluid in the interstitial spaces of the brain during sleep, which they believe may predict the past understanding of the "detoxification" effect of sleep. They believe this may indicate that past assumptions about sleep "detoxification" have been misguided.

  In their experiments, the authors chose special fluorescent dyes as a substitute for the brain's toxic wastes, and they first adjusted the molecular weight of the fluorescent molecules in in vitro diffusion experiments with brain gel models to ensure that the molecules could diffuse reasonably well in the solid brain.

  In preliminary experiments, they injected the fluorescent molecules in the caudate nucleus of mice and confirmed that it was similar to the diffusion process in the gel, and that the fluorescent molecules would peak in the frontal cortex after 6-7 hours and gradually disappear.

  They then observed the dynamics of the fluorescent molecules in mice in different states, and the authors collected brain samples from the mice three or five hours after the fluorescent molecule injection, respectively. According to the comparison, the efficiency of fluorescent molecule clearance was reduced by about 30% in mice in the sleeping state and 50% in the anaesthetised state compared to mice that remained awake. They concluded that the efficiency of waste removal in the brain decreases during sleep and anaesthesia.

  The research team gave an example and compared it to another similar study in the past. An earlier paper published in Science also looked at their changes in cerebrospinal fluid with the help of fluorescent dyes, which found that fluorescent molecules penetrated further from the medullary pool of the cerebellum and even into the cortex when injected during sleep, and suggested that the molecules would move faster and the clearance activity should be more active during sleep.

  However, Professor Franks has a different view in the new study. He believes that the concentration of fluorescent molecules in any given brain region can be explained in terms of a faster rate of entry, but can actually be explained in terms of a slower rate of exit; in other words, the fluorescent molecules observed in the cortex in the study are likely to be the result of a slower rate of exit, which does not result in a timely exit. This explanation would hold true for other similar research approaches.

  However, the authors also say that the findings of the new study need to be taken further, and that more experiments are needed in the future to confirm the exact mechanism and cause of the slowing down of sleep "detoxification", as well as the applicability of the conclusions from the experiments in mice to humans.

  They emphasise that the new study does not deny the importance of sleep, but rather offers a new perspective on past theories of lymphoid clearance, Professor Franks explains: "For example, sleep disruption is a common symptom in people with dementia, and a good night's sleep does help to reduce the risk of dementia, but it may not be through the removal of toxins, as has been thought in the past. "