CSF acts as a cushion that protects the brain from shocks and supports the venous sinuses primarily the superior sagittal sinus, opening when CSF pressure exceeds venous pressure. It also plays an important role in the homeostasis and metabolism of the central nervous system. Protein concentration in cisternal and ventricular CSF is lower. Normal CSF contains mononuclear cells. The CSF pressure, measured at lumbar puncture LP , is mm of H2O mm Hg with the patient lying on the side and mm with the patient sitting up.
Unlike other organs and tissues, the endothelial cells that line brain capillaries have no fenestrations or pinocytotic transportation vesicles and have tight and adherens junctions that almost fuse adjacent endothelial cells. Moreover, these endothelial cells have different receptors and ion channels on their surface facing the lumen than on the surfaces facing the brain, an arrangement that facilitates transcellular transport.
This anatomy is the basis of the blood-brain barrier BBB. The endothelial cells are surrounded by a basement membrane made up of collagens, laminins, and proteoglycans. A discontinuous layer of pericytes are embedded in this basement membrane. Astrocytic processes rich in Aquaporin 4 AQP4 cover the capillaries. The space between them and the capillary basement membrane contains a few perivascular macrophages and rare lymphocytes that cross the BBB passing through endothelial cells rather than between them and survey this space.
The same types of cells are present in the perivascular Virchow-Robin space see below. Brain endothelial cells do not express leukocyte adhesion molecules LAMs on their luminal surface and this limits the entry of leukocytes into brain tissue.
During development, astrocytes induce brain endothelial cells to develop in this special leak-proof fashion. It controls the traffic of molecules, including ions and water in and out of the brain and plays an important role in supplying the brain with nutrients and getting rid of waste and toxic products.
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 do, and small lipophilic molecules such as O2 and CO2 diffuse freely.
Hydrophilic substances can only get across brain capillaries through endothelial cells rather than between them. Some hydrophilic molecules, including glucose and amino acids, enter endothelial cells with the help of transporters, and larger molecules, including proteins, enter via receptor-mediated endocytosis and exit along the opposite surface by exocytosis.
GLUT1 is the glucose transporter. The ATP-binding cassette ABC transporters are important for transport of lipophilic substances and efflux of toxic metabolites. The BBB protects the brain from toxic substances but also impedes the entry of drugs. Circulating leukocytes enter the brain by passing through endothelial cells rather than between them.
Astrocytes cover almost the entire surface of brain capillaries; they are interposed between the vasculature and neurons thus linking neuronal activity to BBB function. Hypertonic stimuli and chemical substances including glutamate and certain cytokines can open the BBB. Astrocytic processes express Aquaporin 4, another water channel that facilitates transport of water. A wide variety of disorders including stroke, trauma, CNS infections, demyelinative diseases, metabolic disorders, degenerative diseases, and malignant brain tumors are associated with BBB dysfunction.
The common end result of BBB dysfunction in many of these disorders is increased vascular permeability leading to vasogenic edema. For instance, blood vessels in glioblastom and other malignant brain tumors do not have tight junctions, explaining the fluid leakage and cerebral edema that accompanies these tumors. Cytokines generated during infectious and inflammatory processes enhance transmigration of circulating leukocytes and may even loosen tight junctions, thus facilitating the migration of inflammatory cells into the brain.
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 interdigitating astrocytic processes with an overlying basement membrane.
This layer seals the surface of the CNS and dips into brain tissue along the perivascular space see below. 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. The major cerebral arteries and veins traverse the subarachnoid space and penetrate into the brain, where they branch into smaller vessels and eventually capillaries. Capillaries are in contact with astrocytic processes.
Vessels larger than capillaries are separated from the surrounding brain tissue by a space the perivascular or Virchow-Robin space , which is an extension of the subarachnoid space.
The glymphatic system helps rid the brain of waste products. Such products are filtered through the arachnoid villi and removed by the venous circulation. Additionally, it has become apparent in recent years that there is a system of lymphatic vessels closely associated with the dural sinuses. This system may also be important for clearing waste products and for immune surveillance. The outer surface of this perivascular space PVS is formed by the glia limitans.
This accumulation of CSF increases the pressure in the brain causing the ventricles to enlarge and the brain to be pressed against the skull.
CSF is primarily produced within the lateral the third ventricles by delicate tufts of specialized tissue called the choroid plexus.
In some cases, hydrocephalus can develop when the choroid plexus produces too much CSF. This can happen when there is a tumor on the choroid plexus, for example. CSF flows from the lateral ventricles through two narrow passageways into the third ventricle. From the third ventricle, it flows down another long passageway known as the aqueduct of Sylvius into the fourth ventricle.
From the fourth ventricle, it passes through three small openings called foramina and into the subarachnoid space surrounding the brain and the spinal cord. If the flow of CSF at any of these points is blocked, hydrocephalus can develop.
This is often referred to as non-communicating hydrocephalus. It has traditionally been thought that CSF is absorbed through tiny, specialized cell clusters called arachnoid villi near the top and midline of the brain. The CSF then passes through the arachnoid villi into the superior sagittal sinus, a large vein, and is absorbed into the bloodstream.
Iskandar, M. Deopujari, M. Muzumdar, M. Badami, B. Authors Andrew Jea, M. Section Editor Shlomi Constantini, M. Editor in Chief Rick Abbott, M. It is believed that CSF is an ultrafiltrate of plasma that enters the basal side of the choroid epithelium and by active metabolism is transformed into CSF and secreted at the apical or ventricular side of the epithelium. This mechanism of CSF formation is largely speculative. The total CSF volume in the ventricles and subarachnoid space is age-dependent but reaches the adult volume of ml by age 5 years.
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