Cerebrospinal fluid was not really discovered in terms of its liquid state of matter until the early 16th century A.D. It took three more centuries for physicians to become aware of its cerebrospinal location. Previously, it was thought that cerebral ventricles contained “spiritus animalis” (spirit of the animal).
Cerebrospinal fluid, occupying the subarachnoid space, is elaborated in an active process by the choroid plexus. It supports the brain and spinal cord and acts in lieu of a lymphatic system for central nervous tissue. Whether or not absorption of CSF into dural venous sinuses is an active or passive process is still controversial. A very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space. There appears to be potential in man for flow of cerebrospinal fluid into the perilymphatic space of the inner ear, but it seldom occurs 3).
Cerebrospinal fluid (CSF) is continuously produced at a 0.4-ml per-minute rate with an average rate of 20-ml per-hour.
CSF flows in a pulsatile manner, dependent on the cardiac rhythm. CSF, being associated with increasing intracranial blood flow and pressure in the cardiac systole, made from the cerebrum, passes through the lateral ventricles by means of Foramen of Monro to the third ventricle, then to the fourth ventricle by the aqueduct cerebri, and to the pontine by passing through the cistern and flows within the spinal canal in the subarachnoid gap. In diastole, there is a return flow toward the lateral ventricles.
The CSF contains approximately 0.3% plasma proteins, or approximately 15 to 40 mg/dL, depending on sampling site, and it is produced at a rate of 500 ml/day. Since the subarachnoid space around the brain and spinal cord can contain only 135 to 150 ml, large amounts are drained primarily into the blood through arachnoid granulations in the superior sagittal sinus. Thus the CSF turns over about 3.7 times a day. This continuous flow into the venous system dilutes the concentration of larger, lipid-insoluble molecules penetrating the brain and CSF.
CSF pressure, as measured by lumbar puncture (LP), is 10-18 cmH2O (8-15 mmHg or 1.1-2 kPa) with the patient lying on the side and 20-30 cmH2O (16-24 mmHg or 2.1-3.2 kPa) with the patient sitting up.
In newborns, CSF pressure ranges from 8 to 10 cmH2O (4.4–7.3 mmHg or 0.78–0.98 kPa). Most variations are due to coughing or internal compression of jugular veins in the neck. When lying down, the cerebrospinal fluid as estimated by lumbar puncture is similar to the intracranial pressure.
The brain produces roughly 500 mL of cerebrospinal fluid per day. This fluid is constantly reabsorbed, so that only 100-160 mL is present at any one time.
Ependymal cells of the choroid plexus produce more than two thirds of CSF. The choroid plexus is a venous plexus contained within the four ventricles of the brain, hollow structures inside the brain filled with CSF. The remainder of the CSF is produced by the surfaces of the ventricles and by the lining surrounding the subarachnoid space.
Ependymal cells actively secrete sodium into the lateral ventricles. This creates osmotic pressure and draws water into the CSF space. Chloride, with a negative charge, moves with the positively charged sodium and a neutral charge is maintained. As a result, CSF contains a higher concentration of sodium and chloride than blood plasma, but less potassium, calcium and glucose and protein.
The influence that human CSF has on the function of human adipose-derived MSCs (hAMSCs) and human fetal-derived NPCs (hfNPCs) in regard to cell proliferation, survival, and migration demonstrated that human noncancerous CSF promoted proliferation and inhibited apoptosis of hAMSCs and hfNPCs. Preculturing these stem cells in human CSF also increased their migratory speed and distance traveled. Furthermore, insulin-like growth factor-1 (IGF-1) in human CSF enhanced the migration capacity and increased the expression of C-X-C chemokine receptor type 4 (CXCR4) in both stem cell types. These findings highlight a simple and natural way in which human CSF can enhance the proliferation, migration, and viability of human exogenous primary hAMSCs and hfNPCs. This may provide insight into improving the clinical efficacy of stem cells for the treatment of CNS pathologies 4).