Donald Glassey, M.S.W., D.C., L.M.T.


© Copyright 2010


It is hypothesized that neuroglial cells, the connective tissue of the nervous system, are much more than supporting cells for neurons. They are by far the most numerous cells in the brain, and also serve a nutritive function for the nervous system. (Guyton 2000) Neurophysiologists also claim there is some evidence that neuroglial cells form a communication network of their own (Restak 1979), the function of which has not been discovered. The theory proposed is that the neuroglial cell system is a communication and transportation network, which serves as the major pathway for hormones, neurotransmitters, releasing factors and other neuropeptides throughout the central nervous system (CNS).  In fact, the manner in which these neuropeptides circulate throughout the body makes the CNS communication system resemble the endocrine system where hormones travel throughout the body. (Pert 1997)

This would suggest that the significance of neuroglial cells is equally important after the birth process as it is in utero. In the developing fetus, the growing sensory axons parallel and follow the lead of the previously formed neuroglial cells, their supportive and nutritive partners.  It is presumed that in the developing fetus neuroglial cells carry chemical messages from the skin, which then match chemical tags at each ascending level of the spinal column and the brain.  These chemical messages identify the appropriate nervous system connections and permit the chemically coded axon to follow its neuroglial cell partner. (Juhan 1998)   

It is proposed that neuroglial cells play an equally pivotal role throughout life as the major pathway for neuropeptide messenger molecules.  It is neuropeptides, which carry messages primarily from the brain to coordinate almost all physiological and emotional processes of the body on a cellular level.  Neuroscientists agree that the cerebrospinal fluid (CSF) is one of the major pathways or medium for neuropeptides circulating around the brain and spinal cord, and that neuropeptides also circulate in the blood and extra cellular fluid and spaces. (Pert 1997) Neuroscientist also suggest that CSF flow may carry important signals for sleep, appetite and sex.  And that there is evidence that CSF may comprise a river of information within the CNS. (Travis 1999)

Although the abovementioned theories have yet to be proven, there are numerous examples which highlight and document the plausibility of these theories.  The suprachiasmatic nuclei (SCN), a small region of the brain that controls the circadium rhythm in humans, has been found to rhythmically secrete the hormone vasopressin into CSF.  Other neuropeptides that stimulate growth of nerve cells can depart from the CSF and diffuse through brain tissue.  It has also been suggested that the hormone melatonin produced by the pituitary gland may be secreted directly into CSF.  (Travis 1999)  Another hormone, oxytocin, which is responsible for maternal bonding behavior, also flows within the CSF.  (Fields 2009)

The abovementioned scientific theories do not explain, however the mechanism by which neuropeptides circulating in the CSF pathway get beyond the dural sleeves of vertebrae at the intervertebral foramina to receptor sites on cells outside of the central nervous system (CNS). Presumably they must travel outside the CNS in order to effect changes in cellular processes in peripheral areas of the body; however, the exact mechanism is unknown. The other possibility is that blood and extracellular fluid are the only pathways for peripheral circulation of neuropeptides. However, it is theorized that cerebrospinal fluid is the primary pathway, and that blood and extracellular fluid are secondary pathways for neuropeptides.  

The theoretical mechanism is that the “hollow” tubules of the connective tissue fibrils of neuroglial cells are not hollow at all, but are filled with a constituent of flowing CSF. (Erlingheuser 1959)  It is suggested that neuroglial cells, which are found throughout the body parallel to and contiguous with all neurons as their supportive structure, (Guyton 2000) form part of a internal communication system for neuropeptides to reach receptor sites on each and every cell in the human body.  

The abovementioned proposition is based on a theory first presented by Ralph F. Erlingheuser, D.O. in 1959 in an article entitled “The Circulation of the Cerebrospinal Fluid through the Connective Tissue System”. Dr. Erlingheuser’s theory was based on research utilizing the then new electron microscope, which showed that the very structure of collagen fibrils offered a new concept for the movement of all tissue fluids. (Erlingheuser 1959) Dr. Erlingheuser’s hypothesis was that since only one-third of the total volume of the 500 ml (about one pint) of CSF produced every day is flowing around the brain and spinal cord, there must also by peripheral flow as well. (Erlingheuser 1959)  Dr. Erlingheuser’s theory was an expansion on the historical osteopathic theory of peripheral circulation of CSF, but did not include any mention of neuropeptides, which were first discovered in the 1980’s.  

Studies cited by Dr. Erlingheuser report the plausibility of a component of CSF flowing outside of the CNS utilizing research from the early use of electron microscopes. (Erlingheuser 1959) Historically, the osteopathic theory proposed that CSF circulated in the periphery of the body between neurons and their epineurium covering in a manner similar to the central circulation between the meninges around the brain and spinal cord. (Upledger 2000) In the 1970s Dr. John Upledger, the founder of CranioSacral Therapy, was involved with research done by Irvin M. Korr, Ph.D, physiologist in the Biomechanics department of Michigan State University. Radioactive tracers were injected into the lateral ventricles of guinea pigs and radioactivity was found throughout the length of the spinal cord, the dural tube, and out the dural sleeves as far as the “IVF”. (Upledger 1998). Based on this research, CSF was not found to flow beyond the dural sleeves at the CNS nerve trunks into the periphery of the body.  

Although Dr. Upledger does not completely discount the possibility of a constituent of CSF in peripheral circulation, he does not think the abovementioned osteopathic theory is a valid mechanism based on the cited research. (Upledger 1998) However, the aforementioned research does not preclude the theoretical possibility of CSF flowing in a neuroglial communication-transportation system parallel to neurons of the peripheral nervous system. The radioactive tracers (isotope) may have been too large to penetrate the glial system at the point of entry of CSF, which is elaborated on later in this article. It is proposed that because most neuropeptides are produced in the brain, where CSF also originates, (Pert 1997) that the major pathway for neuropeptides is cerebrospinal fluid. It is further suggested that neuropeptides enter the blood circulation and extracellular spaces through the cerebrospinal fluid.  

Several recent research projects have demonstrated that “CSF” is the interstitial fluid of the brain and spinal cord. (Upledger 2000) This means “CSF” permeates the spaces between all the nervous and glial cells of the brain and spinal cord. Also neuroglial cells are the largest number of cells in the brain and constitute its structural matrix. The glial cells support every neural fiber and comprise the ground substance for the intercellular metabolic functions of the neurons. The semi-permeable membranes of the glial cells provide their neuron partner with nutrition, and eliminate waste products between nerves and capillaries as well as transmit white blood cells and antibodies to protect the irreplaceable neurons. (Juhan 1998) Thus, it is proposed that glial cells are a “microcosm” in their importance to the neurons, analogous to the “macrocosm” of the cerebrospinal fluid’s importance to the brain and spinal cord.  Scientists have discovered that glial cells have their own communication network, which operates parallel to the communication among neurons.  Glial cells also provide insulation for neurons, and even regulate the flow of information between neurons.  Also glial cells within the brain play a role in sleep and sexual behavior.  (Fields 2009)  It is suggested that there are two possible mechanisms through which CSF could enter the neuroglial transportation-communication system. Both mechanisms would involve the specialized neuroglial cells called astrocytes.

Cerebrospinal fluid is weeped from the blood into the ventricles of the brain primarily by the choroid plexus in the lateral ventricles, and secondarily from the third and fourth ventricles from ependymal cells line that those ventricles. (Guyton 2000) The blood supply to the choroid plexus is from small branches of the internal carotid arteries. These small blood vessels are attached to neurons by astrocytes, which support both the neurons and the blood vessels. (Guyton 2000) This mechanism suggests that CSF could also enter the astrocytes at the same time as it is secreted into the lateral ventricles via the blood supply to the choroid plexus.  

Once entering the astrocytes, a component of CSF could then be transported into the periphery of the body by the communication-transportations system of the neuroglial cell system. This mechanism could account for the other two-thirds of CSF of the total volume produced every day, which is not in circulation around the brain and spinal cord of the CNS. Also, although there is a complete turnover of CSF four or five times a day, two times as much is produced as is absorbed in each cycle. (Upledger 1998) Consequently, peripheral flow of CSF could explain this hypothetical physiological disparity.  

The flowing CSF is primarily absorbed into the blood through the arachnoid villi of the superior sagittal sinus cavity at the top of the cranium, and to a lesser extent through the arachnoid granulation bodies called pachionian granulations. (Upledger 1998) The CSF is absorbed, in both cases, through the dural envelope which suggests flow, not only in the sub-arachnoid space (Guyton 2000), but also in the space between the arachnoid and dura mater, i.e. the sub-dural space.  (Upledger 1998) 

It is theorized that CSF flows in a caudal direction in the sub-dural space between the dura and arachnoid maters, beginning at the foramen magnum and terminating at the second sacral segment, which is the inferior most aspect of the lumbar cistern.  It is further hypothesized that CSF flow in a cephalic direction is in the sub-arachnoid space starting at the second lumbar vertebrae, which is the superior most aspect of the lumbar cistern.  The above theories are plausible because in most adults over the age of 30 the central canal of the spinal cord is probably not patent, which prevents any CSF flow within it.  Therefore, the above mentioned theory explains caudal flow of CSF as well as cephalic flow in the sub-arachnoid space. 

It is also theorized that cerebrospinal fluid flowing in the sub-dural space enters the neuroglial cell system at the junction of the posterior horn and posterior nerve root. Neuroglial cells form a cap over the extremity of the posterior horn forming the substantia cinerera gelatinosa. (Grays 1995) It is proposed that this neuroglial cell cap is the site where CSF enters the neuroglial cell system. It is further theorized that CSF enters first the posterior nerve roots and then the spinal nerve root’s glial cell partner, and continues into peripheral flow through the neuroglial cell system.

Astrocytes support neurons and small blood vessels by attaching neurons to the vessels and hold them close together. The astrocyte forms a wall around the blood vessels in the nervous system and forms a blood-brain barrier. This blood-brain barrier prevents the passage of large molecules in the blood from entering into the nervous system by the selective permeability of the blood vessel membrane. (Upledger 1999) Brain capillaries are supported on all sides by the “glial feet” of astrocytes, which are small projections that abut against all surfaces of the capillaries, and provide physical support to prevent overstretching of the capillaries. (Guyton 2000) However, it is suggested that the selective permeability of the brain capillary membrane could permit the movement of the very small, low molecular weight neuropeptides in the “CSF” to enter the blood. And since the astrocytes are immersed in “CSF”, (Guyton 2000) it is theorized that there is also an exchange of neuropeptides in the “CSF” into these specialized glial cells that could then allow the movement of neuropeptides into the circulatory system. 

It is further proposed that the CSF glial cell transportation system for neuropeptides involves the following pathway; the information message of the neuropeptide enters the cell membrane and goes through a lattice work of glycoproteins in the cell membrane and cytoplasm to penetrate the nucleus of the cell. These glycoproteins are linked by the “hollow” tubules of extracellular collagen fibers to the larger myofibril arrays of the myofascial system surrounding the cell by a framework of fibronectins, which cross-link to the collagen fibers. (Oschman 2000)  

It is also theorized that neuropeptides travel to “target” cell receptor sites in response to environmental signals (physical sensations and emotional feelings). It is further suggested that the mind-body’s perception of the environmental and subsequent behavioral responses are mitigated through neuropeptides, which control almost all physiological and emotional processes. (Pert 1999) Once entering the cell through the thousands of constantly “opening and closing” receptor sites in the cell membrane, the neuropeptide information molecule goes through glycoproteins and readies the nucleus of the cell.  

The 46 chromosomes in the nucleus of the cells are made up of 50% protein and 50% DNA. The genes are composed of a DNA core surrounded by a protein sleeve. The proteins in the sleeve change shape by a process called “signal transduction”, where environmental signals alter the read-out of the genetic code (DNA) by changing the regulatory proteins in the sleeve surrounding the DNA. This process is called epigenetic (above genetic) control where environmental signals control cell behavior and not the DNA. The DNA template is merely a blue print for generating proteins. Messenger RNA makes a copy of the protein to “export” into surrounding cells, tissues, glands, organs, and systems of the body to bring about physiological changes. (Lipton 2005) 

It is theorized that another possible mechanism for CSF entering the neuroglial system is at the point where it is absorbed into the blood supply after flowing around the cerebrospinal axis.  Cerebrospinal fluid is absorbed into the blood supply within the dural envelope though the arachnoid villi in the superior sagittal sinus, and to a lesser extent through the arachnoid granulation bodes called pacchonian granulations. (Upledger 1998) These small venous blood vessels are also attached to neurons by astrocytes, and this could allow a constituent of CSF to enter the neuroglial system instead of being absorbed into the venous blood.  This latter mechanism could be another explanation for the large volume of CSF that is unaccounted for, in terms of the previously stated fact that twice as much of CSF is weeped from the arterial blood supply as is absorbed into the venous blood on a daily basis. (Guyton 2000) 

Additional evidence for a theory of peripheral flow of a component of CSF is proposed in the lymphatic drainage work of Bruno Chikly, M.D.  Dr. Chikly reports that some constituents of CSF in animals drain into cervical lymph nodes. (Chikly 1999) He also suggests that clinical observations indicate that some components of CSF are absorbed in the periphery of the body by the lymphatic system. (Chikly 1999) This theory would lend credibility to peripheral flow of a constituent of CSF.  It would also propose another theory of how the additional amount (two times as much) of CSF produced each day as is absorbed into the venous system, could then be absorbed into the peripheral lymphatic system. Also if Dr. Chikly’s aforementioned theory is correct, and there is an interchange between the CSF and lymph, then neuropeptides could also enter lymphatic vessels as the cerebrospinal fluid is absorbed into the lymphatic system.  (Chikly 1999)  

Finally, it is theorized that a component of CSF flows into the periphery of the body via the neuroglial communication-transportation system. The abovementioned mechanisms could also explain how neuropeptides reach their receptor sites on cells throughout the body. This neuroglial cell system theory proposes another mechanism of how neuropeptides enter the blood supply via astrocytes, as well as entering the lymphatic system. Therefore, it is also further suggested that the cerebrospinal fluid not only serves as a transportation system for neuropeptides, but that its flow within neuroglial cells may form an internal communication network working synergistically with all other body systems.  

In conclusion the scientific importance of neuropeptides and their cerebrospinal fluid pathway substantiates the cogent statements made about CSF by two of the masters of healing arts of the 20th century.  Although neuropeptides were discovered after their time, A.T. Still, the found of Osteopathy, and Dr. Randolph Stone, the founder of Polarity Therapy, were prescient and saw CSF perhaps the most important fluid in the body.  A.T. Still referred to CSF as “the great river of life” (Sutherland 1990), and Dr. Stone called it “the liquid medium for the Breath of Life”. (Stone 1986)





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Dr. Don Glassey, M.S.W., D.C., L.M.T.