Brain Cleans Itself During Sleep; Scientists Image Cerebral Fluid Flow With Neurolucida

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With some exceptions, humans and animals prefer to live in an environment free of filth. We clean our bodies and our homes so we can live healthy and productive lives. It turns out, the brain does too.


Researchers at the University of Rochester discovered that the brain cleans itself during sleep—explaining one of the major reasons we partake in a nightly ritual that has mystified scientists for centuries.


“Sleep has a critical function in ensuring metabolic homeostasis,” Dr. Maiken Nedergaard et al say in their paper published in Science. “The restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.”


Instead of a lymphatic system, the brain has what the researchers call a “glymphatic system.” Waste products that build up during waking hours flush out through the membranes of glial cells in the brain’s interstitial space as cerebral spinal fluid (CSF) flows in. In the process, proteins like b-amyloid, which are associated with Alzheimer’s disease, are washed away. The exchange of fluids occurs along the brain’s vasculature; CSF flows in around arteries, while interstitial fluid (ISF) exits in the space around veins.


To visualize this system, the researchers injected tracers into the brains of mice, dying the different types of fluid either red or green. With two-photon microscopy, they captured vibrant images illustrating the movement of CSF and ISF through the mouse brain. Using Neurolucida, they traced and reconstructed cerebral veins and arteries, as well as the influx of CSF tracer, to create a 3D representation of the mouse brain vasculature that shows the cleansing process in action.

Their visualizations reveal that the process occurs during sleep—a period when the neural signaling that “wakes up” the brain is inactive, cell size is decreased, and interstitial space is increased by 60 percent, allowing for easier flow of fluids.


Since they also witnessed the cleansing process occurring in anesthetized mice, they deduced that the process is related to the sleep-wake cycle rather than the circadian rhythm.


“The purpose of sleep has been the subject of numerous theories since the time of the ancient Greek philosophers,” the authors say in their paper. “An extension of the findings reported here is that the restorative function of sleep may be due to the switching of the brain into a functional state that facilitates the clearance of degradation products of neural activity that accumulate during wakefulness.”


Xie, L., Kang, H., Xu, Q., Chen, M., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D., Nicholson, C., Iliff, J., Takano, T., Deane, R., and Nedergaard, M., Sleep Drives Metabolite Clearance from the Adult Brain, Science 18 October 2013: 342 (6156), 373-377  DOI:10.1126/science.1241224 


Video: A 3D rendering of cascade blue-labeled vasculature of a mouse brain showing the influx of cerebral spinal fluid tracer during sleep. Courtesy of first author Lulu Xie, Ph.D.