Dr. Nora Volkow is among the top neuroscientists in the world. As the current Director of the National Institute of Drug Abuse and former Director of the National Pet Scan Lab at Brookhaven NY, her understanding of the neurobiological basis for addiction and other brain diseases is unsurpassed.
As a friend and colleague for over 30 years, we have worked together in translational research and training medical doctors and other health professionals in addictive disease. In her latest scientific contribution, Volkow and colleagues provide an analysis of what has been termed the “glymphatic” pathway. The role of this newly discovered system in the brain is not unlike the lymphatic system present in other major organs. The name “glymphatic” is derived from this similarity, plus the important role of the brain’s “glial” cells in removing metabolic waste from the central nervous system (CNS) during sleep. Thus the term, G-Lymphatic.
How the Brain Removes Potentially Toxic Waste
This paper addresses potentially significant implications regarding our understanding of neuroanatomy. Here’s why. The brain is protected from our body’s systemic circulation systems by the blood-brain barrier (BBB), which is formed by endothelial cells with tight, non-porous junctions, making it nearly impermeable, even to the smallest ions. It had been thought of as “closed system” not unlike the pressurized AC system in a car. This has created a formidable obstacle for developing therapeutics that target certain brain nuclei or systems. Yet we know that the brain uses and metabolizes most of the body’s glucose for its fuel. So how does the metabolism work? What happens to the expended metabolites?
This excellent analysis suggests that cerebrospinal fluid (CSF) plays a major role in the removal of soluble organic waste, including tau, lactate and other waste in order to prevent their accumulation to toxic levels (Lundgaard et al, 2016). But how? The exact drainage routes are still a matter of debate, yet scientists generally agree that elimination involves parenchymal CSF exchanges with interstitial fluid (ISF). This CSF-ISF mix expedites removal, which is most likely transported via a dedicated perivascular network during sleep. This is very interesting because it has been established that CSF production varies with circadian rhythm, which peak in humans after approximately 2-3 hours of normal sleep. (Nilsson et al 1992).
Why Does This Matter?
Sleep disorders and sleep dysfunction are associated with increased risk for numerous pathologies, including neurodegenerative disorders and autoimmune disease. It follows then, that neurodegenerative disorders may also arise due to disease of the glymphatic system.
Disruption of the glymphatic brain function can result from increased intracranial pressure, damage to the vascular system, and/or disorders that interfere with sleep mechanisms. Which begs the question—what happens to those with serious sleep disorders, like insomnia? Or those who regularly “pass out” for 8-10 hours due to intoxication, but rarely experience a normal sleep cycle?
It is also established that SUD and drug withdrawal can cause marked disruption in the sleep cycle, which over time, is associated with increased psychopathology (depression, anxiety, irritability, mood swings, cognitive decline…). These same symptoms are also common in degenerative disease such as Alzheimer’s disease and CTE, which result from the accumulation of plaque like proteins such as TAU. I would encourage screening SUD patients, especially those reporting a history of sleep and mood disorders, for neurological deficits. It’s just good clinical practice.
This paper presents us with many compelling questions for further research. If we find a causative relationship between SUD, Sleep Disorders and Glymphatic Dysfunction, then treatments that expedite the metabolism and disposal of neuro-waste products could not only help those with addictive disease but also potentially help those with neurodegenerative disease. Time will tell.