Intermittently Increased CO2 Levels Promote Glymphatic Drainage of Metabolic Waste from the Aging Brain
The vessels of the glymphatic system run parallel to blood vessels entering the brain. Glymphatic vessels provide a path for drainage of cerebrospinal fluid into the body. This is a way to remove metabolic waste from the brain, such as the protein aggregates that contribute to neurodegenerative conditions. Loss of glymphatic flow is a feature of aging, allowing the build up of metabolic waste in the brain and consequent cellular dysfunction. Researchers here report on interesting results from a relatively simple approach to restore a greater drainage of cerebrospinal fluid through the glymphatic system, intermittently changing gas levels known to affect blood vessel contraction and dilation in order to encourage fluid flow in the glymphatic system close to those vessels. It remains to be seen as to whether this will affect disease progress, but animal studies of other ways to increase drainage of cerebrospinal fluid are encouraging.
A unifying feature of neurodegenerative conditions is the accumulation of unwanted proteins in the brain. For Alzheimer's disease it is amyloid beta and Tau proteins, while for Parkinson's disease it is alpha synuclein. Related conditions such as Lewy body dementia have a similar protein buildup. Normally, the body can clear these proteins, which are often the waste products of neuron activity, using a natural process called glymphatic clearance, which takes place when our bodies enter deep sleep.
During this process, the brain tells cerebral blood vessels to dilate and constrict, which allows the cerebrospinal fluid that surrounds the brain to flow deeper into the tissue as interstitial fluid. A cycle of blood vessel dilation and contraction pumps the interstitial fluid through the brain and then back out, flushing potentially harmful proteins, inflammatory mediators, and waste into the blood so the body can clear them out. This process takes place at night, when it will not impact more complex synaptic function, which is also when the brain's neurons dump out their waste products. Indeed, many scientists believe glymphatic clearance is one of the reasons we need to sleep in the first place.
In a study conducted with 30 patients with Parkinson's disease and 33 healthy controls, researchers used MRI brain scans during sleep to figure out the frequency of oscillation between blood vessel dilation and contraction during glymphatic clearance. They then had study participants breathe in a mixture of 5% carbon dioxide (CO2) and normal air, alternating with normal room air every 35-seconds. After just one half-hour session of the new treatment, the researchers detected higher concentrations of proteins such as beta amyloid, alpha synclein, and other byproducts of brain activity in the blood, indicating these waste products had been flushed out of the brain and into the blood, allowing the body to clear them.
If lowering the CO2 levels in blood constricts the vessels in the brain, the opposite could also be true. Increasing CO2 levels could cause the vessels to dilate, and alternating raising and lowering the CO2 level would generate the pumping action needed to propel the interstitial fluid across the brain.