Nr. 5
The Mystery of Nocturnal Brain Cleaning 🔍
The sleep habits of my brother Sherlock Holmes were always a mystery. When absorbed in a case, he could go days without sleep or food. His mania for sleepless nights often drove Dr. Watson to despair.
I recall numerous times finding my brother utterly exhausted in a train compartment, where he would be taking a nap. “I haven’t gathered enough data,” he would say, “and I won’t think about the case until I have more information.” Yet, sleep is essential for most people and plays an incredibly important role in our brain health.
🧩 Scientists have now discovered that sleep is not only vital for rest but also indispensable for brain cleaning. While we sleep, fluid flows through the grey cells, flushing out chemical wastes that accumulate during the day. Since the brain lacks its own lymphatic system, scientists only discovered in 2012 how this process works: through the glymphatic system. These specialized drainage pathways surround the brain's blood vessels with so-called aquaporins – water channels created by support cells in the brain known as astrocytes.
🔬 Fresh brain fluid flows through the brain space along the arteries and uses these water channels to distribute itself within the brain tissue. On its journey, it picks up waste products from the tissue. Eventually, the fluid reaches the venous regions of the glymphatic system and is washed out through the lymphatic vessels in the neck into the systemic circulation. This system removes up to 60% of large proteins and dissolved substances, including lactate, β-amyloid, and tau protein, which play a crucial role in the development of Alzheimer’s disease.
🔍 In my latest case from a recent publication, it turned out that the sleeping aid Zolpidem was an unwelcome intruder (Hauglund, N. L., et al. Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. Cell, 2025). It seems that this medication might hinder the regular movements of blood vessels and subsequently the fluid flow, thereby jeopardizing the nightly cleaning operation of our brain.
🕵️♂️ This timeless case led me to the brilliant discoveries of Maiken Nedergaard and her team, who discovered the glymphatic system in 2012. “Most clever,” I muttered while studying the latest research findings. “But how exactly does it work? And why might sleeping aids like Zolpidem impair this function?”
🔬 To get to the bottom of it, scientists implanted electrodes and fiber optic threads in mice so they could sleep naturally. The brain neurotransmitter norepinephrine emerged as the main actor in this cleaning drama. During particular sleep phases known as non-REM sleep, norepinephrine levels rose and fell rhythmically, causing blood vessels to contract regularly and pump brain fluid through the brain tissue. “It’s as if our brain sends out a cleaning crew every night through this mechanism,” I thought with a smile. “Only Zolpidem paralyzes this crew.”
💡 By injecting a fluorescent substance that traced the fluid flow, the scientists could observe the movement of the brain fluid. When they artificially provided mice with norepinephrine and sped up the pulses from 50 seconds to 10 seconds, they found that the fluid penetrated deeper into the brain regions close to norepinephrine production. “Science is truly fascinating,” I thought. “Norepinephrine indeed orchestrates this nocturnal cleaning service.”
⚠️ Unfortunately, Zolpidem turned out to be the villain of this story. It reduced norepinephrine oscillations and significantly decreased the brain fluid flow. “A truly insidious saboteur,” I thought. “It seems that patients taking Zolpidem might impair their nightly brain cleaning.”
🧪 Sleep deprivation hinders the removal of waste products and increases the β-amyloid load in the hippocampus and thalamus after just one sleepless night. A dysfunction of the glymphatic system could explain the connection between chronic sleep deprivation and neurological diseases such as Alzheimer’s and Parkinson's. Moreover, conditions like hypertension, diabetes, obesity, a sedentary lifestyle, disrupted circadian rhythm, and traumatic brain injuries also impair the efficiency of this waste removal system.
🔍 And so, dear readers, I have solved another criminal case in the realm of neurology. Sleep is far more than mere rest; it is a detailed and essential brain cleaning process orchestrated by norepinephrine and the rhythmic contractions of blood vessels. Sleeping aids like Zolpidem might indeed disrupt this crucial function. “The mystery is solved,” I announced. “Stay vigilant and choose your sleeping aids wisely.”🕵️♂️🧠