Abstract
Despite its small size, the brain consumes 25% of the body’s energy, generating its own weight in potentially toxic proteins and biological debris each year. The brain is also the only organ lacking lymph vessels to assist in removal of interstitial waste. Over the past 50 years, a picture has been developing of the brain’s unique waste removal system. Experimental observations show cerebrospinal fluid, which surrounds the brain, enters the brain along discrete pathways, crosses a barrier into the spaces between brain cells, and flushes the tissue, carrying wastes to routes exiting the brain. Dysfunction of this cerebral waste clearance system has been demonstrated in Alzheimer’s disease, traumatic brain injury, diabetes, and stroke. The activity of the system is observed to increase during sleep. In addition to waste clearance, this circuit of flow may also deliver nutrients and neurotransmitters. Here, we review the relevant literature with a focus on transport processes, especially the potential role of diffusion and advective flows.
Highlights
The brain is one of the last frontiers in physiology and medicine, and has been long under-explored due to difficulties and concerns of breaching the cranial vault
Xie et al showed ketamine/xylazine anesthesia to be equivalent to sleep by electrocorticography (ECoG) and electromyography (EMG) recordings, which recorded high prevalence of “delta waves”.) As hydraulic conductivity is known to increase with void volume [33], these results suggest a potential increase in interstitial advective transport with sleep
INPH and 8 healthy controls showed significant signal enhancement across all brain regions spreading centripetally from the cortex inward to the deeper brain [106]
Summary
The brain is one of the last frontiers in physiology and medicine, and has been long under-explored due to difficulties and concerns of breaching the cranial vault. A particular opportunity is integration of data into comprehensive models based on fluid dynamics, material science, transport phenomena, reaction kinetics and thermodynamic fundamentals. The transport of molecules is an essential link in many physiological and pathological processes of the brain. The brain produces metabolic waste at a higher rate than any other organ, making transport of molecules out of the brain (waste clearance) a critical cerebral process [5]. Fluid “leaks” through blood vessel walls, driven by arterial pressure, and flows across the interstitial space that surrounds cells. The interstitial fluid (ISF), containing molecular waste and depleted in nutrients, is collected by lymph vessels, and delivered to the venous circulation where it is carried to the liver and kidneys for processing
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