Brief Communication: Brain Clearance is Reduced During Sleep and Anesthesia
Brain Clearance Mechanism Suppressed During Sleep and Anesthesia
Background
Clearing metabolic wastes and toxic substances from the brain is a crucial process for maintaining a healthy nervous system. However, the specific mechanism of this process has been debated. A widely discussed viewpoint suggests that the sleep state promotes the function of the so-called “glymphatic system”, thereby enhancing the clearance process in the brain. Some researchers have even proposed that long-term sleep deprivation may impair the glymphatic system, exacerbating neurodegenerative diseases such as Alzheimer’s disease. Anesthetic drugs at certain doses have also been considered to enhance brain clearance function. However, this theory remains controversial.
Paper Source
This study was led by Professor Nicholas P. Franks and Professor William Wisden from Imperial College London and published in the journal Nature Neuroscience in 2024.
Research Process
1) The researchers first injected fluorescent molecules into the mouse brain and implanted an optical fiber in the prefrontal cortex to measure the diffusion of the fluorescent molecules. Through photobleaching experiments, they determined the diffusion coefficient of the fluorescent molecules in brain tissue.
2) They found that the diffusion of fluorescent molecules showed no significant difference regardless of whether the mice were awake, asleep, or anesthetized, indicating that diffusion is independent of the state of consciousness.
3) The researchers further measured the clearance rate of fluorescent molecules in the brain. They injected a small-molecule fluorescent dye and measured the change in its concentration over time in the cortical region.
4) The experimental results showed that during the awake state, the brain clearance rate was approximately 70-80%. However, the clearance rate was significantly reduced during sleep or anesthesia, which is contrary to the previous notion that sleep and anesthesia promote brain clearance.
5) Through histological experiments, the researchers further confirmed the above findings.
Main Conclusions
This study refutes the previously widespread notion that sleep and anesthesia promote the clearance of metabolic products and toxins from the brain. Instead, the study found that sleep and anesthesia actually suppress brain clearance function. This finding has important implications for understanding the mechanisms of sleep and the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease.
Research Significance
1) This study directly measured the effects of sleep and anesthesia on brain clearance function and obtained results contrary to previous views, providing valuable insights into the physiological functions of sleep.
2) The study refutes the longstanding belief that sleep deprivation leading to impaired brain clearance function could be one of the causes of neurodegenerative diseases such as Alzheimer’s disease. This helps to re-examine the pathogenic mechanisms of these diseases.
3) The study introduces a novel method for directly measuring the clearance rate of molecules in the brain, providing a powerful tool for investigating brain clearance mechanisms.
4) The research results suggest that improving brain clearance function may require approaches other than simply promoting sleep, providing new perspectives for the prevention and treatment of related diseases.