The human brain is composed of 80% fluid, most of which is cerebrospinal fluid (CSF). CSF is formed at a rate of 500 milliliters (mL) per day by the epithelial cells of the choroid plexus (located in the lateral, third, and fourth ventricles). Once produced by the choroid plexus, CSF flows into the ventricles and the subarachnoid spaces, which surround the brain and spinal cord. Distended regions of the subarachnoid space are called subarachnoid cisterns. Fluid is transferred from CSF to venous blood by one-way bulk flow and is returned to the systemic circulation. In the steady state, the movement of fluid from CSF to venous blood should equal the rate of CSF formation (i.e., 500 mL/day). For diagnostic purposes, CSF can be sampled using a lumbar puncture in the lumbar cistern.
The relationships between the arterial blood supply of the brain, the choroid plexus, and the blood-brain barrier are shown in Figure 3-38. Note that substances can be exchanged between brain cells (which are bathed in interstitial fluid), the interstitial fluid, and CSF.
Figure 3–38 Mechanism for the production of cerebrospinal fluid. CSF, Cerebrospinal fluid.
The barrier between cerebral capillary blood and CSF is the choroid plexus. This barrier consists of three layers: capillary endothelial cells and basement membrane, neuroglial membrane, and epithelial cells of the choroid plexus. The choroid plexus epithelial cells are similar to those of the renal distal tubule and contain transport mechanisms that move solutes and fluid from capillary blood into CSF.
The barrier between cerebral capillary blood and interstitial fluid of the brain is the blood-brain barrier. Anatomically, the blood-brain barrier consists of capillary endothelial cells and basement membrane, neuroglial membrane, and glial end feet (projections of astrocytes from the brain side of the barrier). Functionally, the blood-brain barrier differs in two ways from the analogous barrier in other tissues. (1) The junctions between endothelial cells in the brain are so “tight” that few substances can cross between the cells. (2) Only a few substances can pass through the endothelial cells: Lipid-soluble substances (e.g., oxygen and carbon dioxide) can cross the blood-brain barrier, but water-soluble substances are excluded.
Formation of Cerebrospinal Fluid
CSF is formed by the epithelial cells of the choroid plexus. Transport mechanisms in these cells secrete some substances from blood into CSF (e.g., Na+, Cl−, water) and absorb other substances from CSF into blood. Molecules such as protein and cholesterol are excluded from CSF because of their large molecular size. On the other hand, lipid-soluble substances such as oxygen and carbon dioxide move freely and equilibrate between the two compartments. Thus, depending on the transport mechanisms and the characteristics of the barrier, some substances are present in higher concentration in CSF than in blood, some are present at approximately the same concentration, and some are present in lower concentration in CSF than in blood. Many substances readily exchange between brain interstitial fluid and CSF (see Fig. 3-38); thus, the compositions of interstitial fluid and CSF are similar to each other but different from blood. Table 3-6 compares the composition of CSF and blood.
Table 3–6 Composition of Cerebrospinal Fluid
[CSF] ≈ [Blood]
[CSF] < [Blood]
[CSF] > [Blood]
CSF, Cerebrospinal fluid.
*Negligible in CSF.
Functions of Cerebrospinal Fluid
The functions of CSF are to provide a constant, controlled environment for the brain cells and to protect the brain from endogenous or exogenous toxins. CSF also may function to prevent escape of local neurotransmitters into the general circulation. Depending on their lipid solubility, drugs penetrate the blood-brain barrier in varying degrees. Thus, nonionized (lipid-soluble) drugs penetrate the brain readily, whereas ionized (non–lipid-soluble) drugs do not penetrate. Inflammation, irradiation, and tumors may increase the permeability of the blood-brain barrier and allow substances normally excluded to enter the brain. These substances include cancer chemotherapeutic drugs, antibiotics, and radiolabeled markers.