How Does the Brain Get Rid of Toxic Waste?

SadaNews - For decades, scientists have pondered a fundamental problem: how does the human brain dispose of the waste it generates during work and thinking throughout the day, including excess proteins and molecules that could turn toxic if not removed, including beta-amyloid and tau proteins, which are considered major contributors to Alzheimer's disease.

For other organs in the body, the lymphatic system handles waste disposal, where excess fluids are transferred to the spleen, lymph nodes, and other parts of the lymphatic system before entering the bloodstream to be eliminated. However, this vital process cannot occur in the same way within the brain due to what is known as the blood-brain barrier, a protective covering that prevents infections from reaching the nerve cells inside the brain but similarly prevents the transfer of anything from outside the brain.

Clearing Toxic Waste

In 2012, a research team at the University of Rochester, led by neurologist Maiken Nedergaard, discovered a previously unknown circulatory system for clearing toxic waste from the brain. Research on laboratory mice showed cerebrospinal fluid flowing within tunnels surrounding the blood vessels in the brain, where these channels interact with a type of brain cell known as astrocytes, mixing with what is termed "interstitial fluids," which collect waste and carry it out of the brain through spaces around the blood vessels.

In 2013, Nedergaard published a significant study indicating that the cleaning process activates during the night. The researcher stated to the website "Scientific American" that "during waking hours, the cleaning process stops, likely due to the fact that the precision required for the neural systems that process external stimuli does not align with the washing process."

These findings confirm that the brain's washing process, recently discovered, is one of the key benefits of sleep. She explains, "When you wake up feeling refreshed after a period of quiet sleep, it is likely due to the brain undergoing a reset process similar to what happens during car maintenance."

However, previous studies were conducted on mice, whose brains are much smaller and less complex than those of humans, and their sleep periods are typically fragmented rather than continuous as in humans. Thus, many scientists were skeptical about the theory of brain washing in humans during sleep.

Jonathan Kipnis, a neuroimmunology specialist at the University of Washington, commented, "Ten years ago, talking about fluid flow in the brain seemed like heresy." Researchers have spent the last decade investigating whether the brain washing process occurs in humans similarly to how it happens in mice, and research has confirmed the validity of this theory. In fact, the electrical waves moving within the brain during sleep help push cerebrospinal fluid in and out of the brain.

Jeffrey Iliff, a professor of psychology and neurology at the University of Washington, emphasizes the importance of what is known as the "glymphatic system," referring to the cleaning mechanism of the brain and the removal of waste that occurs during human sleep. He stated in a "Scientific American" interview that any disruption in this system likely leads to neurological and psychological disorders, including Alzheimer's disease. He believes that disruptions in the glymphatic system may explain the accumulation of beta-amyloid and tau proteins in aging brains.

Sleep and Memory Storage

Researcher Iliff noted that sleep specialists have long focused on the importance of sleep in memory storage. Additionally, doctors who have studied the spaces surrounding the blood vessels have not clearly identified their purpose, largely dismissing the possibility that these spaces are actually channels for fluid flow, adding that they "did not realize how dynamic these channels are." Researchers say the human body produces between three to four times its store of cerebrospinal fluid every day, which is then eliminated. Some early studies had recognized a connection between the flow of these fluids and heartbeats; however, previous studies did not clarify how the flow of these fluids changes during sleep.

In an experiment conducted by researcher Nedergaard to measure the rates of amyloid protein clearance during the wakefulness and sleep of mice, researchers injected fluorescent tracers into the brains of the mice to monitor the flow of cerebrospinal fluid in the spaces around blood vessels. They found that the flow of these fluids decreases by 95% during waking hours compared to what occurs during sleep, and that the size of these channels between vessels expands by 60% when the mice are asleep or under anesthesia, indicating that the body undergoes physiological changes during unconsciousness that enhance the brain's ability to dispose of its waste.

In a similar study on humans conducted in 2021, neurosurgeon Pierre-Christian Edy from Oslo University Hospital in Norway injected fluorescent tracers to monitor cerebrospinal fluid flow in a group of volunteer patients, dividing them into two groups. Members of the first group were allowed to sleep normally throughout the night, while members of the second group were kept awake during the same period.

MRI scans were performed on both groups twice during the night and then the following day. The experiment showed that the movement of fluorescent tracers tracking the cerebrospinal fluid flow was significantly slower in volunteers who were not allowed to sleep. It also revealed that even after allowing them to sleep the following night, their cerebrospinal fluid flow rate remained slow compared to the other group, demonstrating that the effects of sleep deprivation cannot be easily compensated for by just sleeping the following night.

Edy confirmed that "despite the glymphatic system functioning differently between humans and mice—where changes in the human brain occur over hours rather than minutes like in mice—it is clear that the human brain also undergoes washing during sleep, and that lack of sleep negatively impacts the functioning of this system."