CSF Production and Normal Contents | The blood-Brain Barrier | Abnormalities of CSF |

THE NORMAL CSFThe cerebrospinal fluid (CSF) is produced from arterial blood by the choroid plexuses of the lateral and fourth ventricles by a combined process of diffusion, pinocytosis and active transfer. A small amount is also produced by ependymal cells. The choroid plexus consists of tufts of capillaries with thin fenestrated endothelial cells. These are covered by modified ependymal cells with bulbous microvilli. The total volume of CSF in the adult is about 140 ml. The volume of the ventricles is about 25 ml. CSF is produced at a rate of 0.2 – 0.7 ml per minute or 600-700 ml per day. The circulation of CSF is aided by the pulsations of the choroid plexus and by the motion of the cilia of ependymal cells. CSF is absorbed across the arachnoid villi into the venous circulation. The arachnoid villi act as one-way valves between the subarachnoid space and the dural sinuses. The rate of absorption correlates with the CSF pressure. CSF acts as a cushion that protects the brain from shocks and supports the venous sinuses. It also plays an important role in the homeostasis and metabolism of the central nervous system.
CSF from the lumbar region contains 15 to 45 mg/dl protein (lower in childen) and 50-80 mg/dl glucose (two-thirds of blood glucose). Protein concentration in cisternal and ventricular CSF is lower. Normal CSF contains 0-5 mononuclear cells. The CSF pressure, measured at lumbar puncture (LP), is 100-180 mm of H2O (8-15 mm Hg) with the patient lying on the side and 200-300 mm with the patient sitting up.

blood-brain barrier
Blood-brain barrier
Unlike other organs and tissues, brain capillaries show no fenestrations or pinocytotic vesicles and have tight junctions that almost fuse adjacent cells. This anatomy creates the blood-brain barrier (BBB). Astrocytic foot processes surround brain capillaries and, during development, induce brain endothelial cells to develop in this special leak-proof fashion. The BBB separates plasma from the interstitial space of the CNS and affects in a critical fashion the traffic of various molecules in and out of the brain. The ability to exclude certain substances from brain interstitial space has to do not only with the vascular anatomy, but also with lipid solubility and selective transcellular transport by endothelial cells. Lipophilic compounds cross the BBB easier than hydrophilic ones and small lipophilic molecules such as O2 and CO2 diffuse freely. Some hydrophilic compounds, including glucose and amino acids, enter the brain with the help of transporters, and larger molecules enter via receptor-mediated endocytosis. The BBB protects the brain from toxic substances but impedes also the entry of drugs. Hypertonic stimuli and chemical substances including glutamate and certain cytokines can open the BBB. HIE and inflammatory mediators produced in sepsis disrupt the BBB. Blood vessels in GBM and other malignant brain tumors do not have tight junctions, explaining the fluid leakage and cerebral edema that accompanies these tumors. The interstitial space of the brain is separated from the ventricular CSF by the ependymal lining and from the subarachnoid CSF by the glia limitans. The glia limitans is a thick layer of astrocytic processes with an overlying basement membrane. This layer seals the surface of the CNS. External to it is the pia matter, a thin layer of connective tissue cells with a small amount of collagen. The ependymal barrier is far more permeable than the BBB.
Blood: Blood may be spilled into the CSF by accidental puncture of a leptomeningeal vein during entry of the LP needle. Such blood stains the fluid that is drawn initially and clears gradually. If it does not clear, blood indicates subarachnoid hemorrhage. Erythrocytes from subarachnoid hemorrhage are cleared in 3 to 7 days. A few neutrophils and mononuclear cells may also be present as a result of meningeal irritation. Xanthochromia (blonde color) of the CSF following subarachnoid hemorrhage is due to oxyhemoglobin which appears in 4 to 6 hours and bilirubin which appears in two days. Xanthochromia may also be seen with hemorrhagic infarcts, brain tumors, and jaundice.
Increased inflammatory cells (pleocytosis) may be caused by infectious and noninfectious processes. Polymorphonuclear pleocytosis indicates acute suppurative meningitis. Mononuclear cells are seen in viral infections (meningoencephalitis, aseptic meningitis), syphilis, neuroborreliosis, tuberculous meningitis, multiple sclerosis, brain abscess and brain tumors.

CSF leukemia
Leukemic cells in the CSFTumor cells indicate dissemination of metastatic or primary brain tumors in the subarachnoid space. The most common among the latter is medulloblastoma. They can be best detected by cytological examination. A mononuclear inflammatory reaction is often seen in addition to the tumor cells.
Increased protein: In bacterial meningitis, CSF protein may rise to 500 mg/dl. A more moderate increase (150-200 mg/dl) occurs in inflammatory diseases of meninges (meningitis, encephalitis), intracranial tumors, subarachnoid hemorrhage, and cerebral infarction. A more severe increase occurs in the Guillain-Barré syndrome and acoustic and spinal schwannoma. In multiple sclerosis, CSF protein is normal or mildly increased, but there is often an elevation of IgG in CSF, but not in serum, expressed as an elevation of the CSF IgG/albumin index (normally 10:1). In addition, 90% of MS patients have oligoclonal IgG bands in the CSF. Oligoclonal bands are also seen occasionally in some chronic CNS infections. The type of oligoclonal bands is constant for each MS patient throughout the course of the disease. Oligoclonal bands occur in the CSF only (not in the serum). These quantitative and qualitative CSF changes indicate that in MS, there is intrathecal immunoglobulin production. In addition, the CSF in MS often contains myelin fragments and myelin basic protein (MBP). MBP can be detected by radioimmunoassay. MBP is not specific for MS. It can appear in any condition causing brain necrosis, including infarcts.

Low glucose in CSF is seen in suppurative, tuberculous and fungal infections, sarcoidosis, and meningeal dissemination of tumors. Glucose is consumed by leukocytes and tumor cells.

Further reading

Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview. Structure, regulation, and clinical implications. Neurobiol Dis 2004;16:1-13.