August 30, 2022 | Henry Richter

The “Empty” Space in the Brain Has Vital Functions

Extra-cellular space (ECS)—the space between brain cells—
has important functions that are ‘mind boggling,’ too.


by Henry Richter, PhD, PE

The body is an unbelievably complex organism, showing so many aspects of complex design. And, of course one of the most complex parts is the brain. A recent article in Physics Today (May 2022, Vol 75, pages 26-32) entitled “The Secret World in the Gaps Between Brain Cells” caught my attention. It was authored by Charles Nicholson, emeritus professor in the department of neuroscience and psychology at the New York University Grossman school of medicine in New York City. The research he describes is absolutely fascinating.

What Is ECS?

It is hard to imagine gaps between brain cells. The human brain has about ten billion neurons, all with several interconnections. This research focuses on the fluid-filled extracellular space (ECS) which has sheets and tunnels between the cells. The fluid consists of a solution of sodium chloride with smatterings of potassium, calcium, several amino acids and peptides. It is not unreasonable to surmise that there must be something between the cells, however, considering there are ten billion cells within the cranium.  That is surely the essence of “crammed together.”

The cells are in patterns of sheets and folds, so they all fit together, and of course, function properly (at least most of the time). Studying the ECS pushes the limit of optical microscopy and also the use of micropipettes and microelectrodes a few micrometers wide. Various solutions with radioisotopes or with fluorescent dies are injected into the ECS and their movement tracked.

Mind the Gaps: A History of Discoveries

Beginning in the nineteenth century to the present brains have been studied. Passages between cells were discovered only after the use of electron microscopes arrived. Study of the ECS became possible after diffusion was understood. Early study was made possible by tracking molecules tagged with radioisotopes which could indicate fluid flow. Then the first in situ measurements were made possible by the development of micropipettes and microelectrodes which reached nanometer dimensions and could be inserted into the intercellular channels.

Specific ions were introduced into the ECS and tracked by electrical currents between the micropipette and microelectrode. Then super resolution optical microscopes arrived on the scene and helped to further characterize the ECS structure. Calculations using diffusion theory took the research another step forward.

The Fluid Flows Purposefully

Understanding the flow in the ECS is important medically to plan drug delivery into brain cells. It also tracks how nutrients are delivered to brain cells and the waste products removed. The ECS terminate on blood vessels for this exchange.

Diffusion was assumed, but advection—the transport of molecules by the fluid—needed to be understood. Around 1980 Helen Cserr of Brown University preformed a different type of tracer experiment, extending over longer times and multiple cells. This showed that different ions with radiotracers of different molecular weights and sizes are cleared from the brain at the same rate. This differentiated diffusion from advection, showing that advection was the preferred mechanism and that flow was constant. The fact of flow has received further support. It seems that flow originates in the perivascular spaces that surround the many blood vessels in the brain. The fluid leaves the perivascular spaces and flows to and from the brain cells.

A Battery and Reservoir

What from all of this? Radiotracers have provided an estimate of the volume of the fluid in the ECS and that is about 15-20% of the brain volume. This fluid plays a vital role in nourishing the cells as well as promoting the electrical connectivity between cells as the brain functions. This result has been confirmed. Similar results have been shown in diverse regions of the brains of rats, mice, humans, some nonmammalian vertebrates, and even octopuses.

Why does the brain have so much ECS? One reason is that in order to exchange electrical signals, nerve cells maintain an electrical potential difference between their insides and outsides, constituting a battery. This requires a reservoir of ions external to the cell which is maintained by active transport of ions across the membranes.

A Cleansing Bath, Nutrient Supplier and Information Carrier

Another projected reason is that substances need to diffuse between cells. Some of these substances such as glucose are needed for cell metabolism. Some are waste products of metabolism. These move to and from the vast network of blood vessels in the brain. Other substances are signaling molecules that pass between the cells.

Finally, dramatic changes in the volume of the ECS has been shown in pathological conditions such as ischemia or stroke when blood is cut off to part or all of the brain. The lack of oxygen and glucose causes the cells to rapidly swell and reduce the ECS. This occurs as some of the interstitial fluid salt enters the cell and water follow suit to maintain the osmotic balance. A minor type of such action is believed to accompany migraine headaches.

Trying to take this all in makes me shout WOW! What fantastic design is involved? And I am sure that we are able to see only a tiny fraction of the marvel that was created to allow life. We will continue to learn more.

Dr. Henry Richter was born in Long Beach, California, and served a short tour of duty in the U.S. Navy in World War II. From there he received a BS and PhD (Chemistry, Physics, and Electrical Engineering) from the California Institute of Technology in Pasadena California. Then he went to the Jet Propulsion Laboratory, which became part of NASA. While there he headed up the development of the free world’s first earth satellite, Explorer 1. He then oversaw the scientific instrumentation for the Ranger, Mariner, and Surveyor Programs. From JPL, he went to Electro-Optical Systems becoming a Vice President and Technical Director. Next was a staff position with UCLA as Development Manager of the Mountain Park Research Campus. He then owned an electronics manufacturing business and afterwards became the Communications Engineer for the L.A. County Sheriffs Department. Since 1977, he has been a communications consultant to Public Safety organizations. He is a life member of APCO, the IEEE, and the American Chemical Society. He was the 2019 recipient of the Lifetime Achievement Award from the Radio Club of America, which he was awarded at their annual banquet in New York City. His book America’s Leap into Space details the origins of rocketry and his own role in the launching of the first American satellite, Explorer 1, in 1958. Henry Richter is also author of Spacecraft Earth: A Guide for Passengers, with co-author David Coppedge (Creation Ministries International, 2016). Creation-Evolution Headlines is honored to have Dr Richter as a contribution writer. See his Author Profile for his previous contributions.

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