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Cerebrospinal fluid A selective review.

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Cerebrospinal Fluid: A Selective Review
Robert W. P. Cutler, MD, and Robert B. Spertell, MD
Technical advances of the past decade permit detection in the cerebrospinal fluid of many endogenous substances
elaborated by the brain. Study of the composition of cerebrospinal fluid in health and disease undoubtedly will
supply clues to the pathophysiology of many neurological disorders.
Cutler RWP, Spertell RB: Cerebrospinal fluid: a selective review. Ann Neurol 11: 1-10, 1982
Formation a n d Absorption
The formation and absorption of CSF in human beings have been measured by indicator dilution techniques during ventriculolumbar or ventriculoventricular perfusions in children and adults [28, 90, 92,
1341. T h e rate of formation is approximately 0.35 ml
per minute, o r 500 ml per day. T h e turnover of CSF,
based on an average volume of 150 ml [97], is therefore 14% per hour. No relationship between formation rate and CSF pressure has been found in patients
with normal-sized ventricles [28]. In a study of children and adults with communicating hydrocephalus,
the rate of formation was the same as that in nonhydrocephalic patients but it declined slightly with
increasing CSF pressure [90]. In hydrocephalus the
turnover of CSF is reduced because the volume of
fluid is increased while formation remains constant.
Reduced turnover of CSF may contribute to defective removal from the CSF of brain metabolites such
as 5-hydroxyindoleacetic acid, which is found at increased concentration in the ventricular fluid of hydrocephalic patients [8]. Such metabolic disturbances
could alter brain function.
The choroid plexus is the principal source of CSF.
In rabbits and cats the plexus is richly innervated by
both cholinergic [36] and adrenergic [86] nerve
fibers. Stimulation of nerves from the superior cervical ganglion reduces CSF formation [86]. Contrarily,
stimulation of a- and P-adrenergic receptors increases CSF formation [62]. These latter changes may
be mediated by cyclic adenosine monophosphate in
the choroid plexus [136]. Cholera toxin, which activates cyclic adenosine monophosphate, stimulates
CSF formation [41], and the effect may be blocked
by the prostaglandin inhibitor indomethacin [43].
Evidence exists for extrachoroidal CSF secretion in
several animal species [19, 102, 1251; the failure to
relieve hydrocephalus by choroid plexotomy provides indirect evidence for extrachoroidal fluid formation in humans. Under some circumstances there
may be flow of fluid from blood to CSF through the
brain [ 1591.
CSF is secreted by an incompletely understood
two-step process [ 1401. First, fluid is filtered through
the highly permeable core capillary of the choroidal
frond into the extracellular space surrounding
choroidal cells. Second, sodium is actively transported across choroidal cells into CSF, and water
follows obligatorily down an osmotic gradient. The
transport of sodium and bicarbonate appear to be
partially linked [ 1571. CSF formation can be reduced
by drugs that inhibit sodium- and potassium-activated
adenosine triphosphatase [ 1551 or carbonic anhydrase [118]. Reduction of secretion by these enzymes
leads to accumulation of interstitial fluid in the
choroid plexus [ 1391.
No clear-cut evidence exists that agents such as
acetazolamide, furosemide, corticosteroids, or cardiac glycosides are of value in reducing CSF formation, nor is it likely that a reduction in CSF formation
would be helpful in the control of intracranial
hypertension in humans.
The rate of absorption of CSF increases linearly
From the Department of Neurology, Stanford University School
of Medicine, Stanford, CA 94305.
Received June 9, 1981, and in revised form July 20. Accepted for
publication July 21, 1981.
This brief review for the clinical neurologist touches
on selected areas in which analysis of the dynamics
and composition of cerebrospinal fluid (CSF) furthers
our understanding of brain disease. T h e CSF is appropriately viewed as the clinician’s access to the
brain and is capable of reflecting pathophysiological
changes in brain function. This idea was first emphasized by Davson, whose 1967 monograph on CSF
physiology has since been the standard text [3 11. The
advances of the past decade have been the subject of
three new texts [45, 170, 1721 to which the interested reader should refer.
Address reprint requests to Dr Cutler.
0364-5134/82/010001-10$01.25 @ 1981 by the American Neurological Association
with CSF pressure at a rate of 7.6 kl/min/mm once a
critical opening pressure of about 70 mm CSF has
been exceeded [28, 761. It is generally agreed that
the major absorptive sites are the arachnoid granulations which penetrate the major dural venous sinuses
in the cranium [ 104, 1601. Arachnoid granulations
have also been found penetrating the epidural veins
in association with spinal nerve roots [163]. Whether
fluid normally is absorbed at the spinal sites is not
known. It is possible in communicating hydrocephalus that activation of spinal as well as transventricular absorptive mechanisms compensates for the
loss of cranial subarachnoid absorptive sites.
The mechanisms by which the CSF and its constituents are absorbed in bulk through the arachnoid
villi are unknown. Early anatomical studies suggested
that the villus comprised a series of tubules directly
connecting the subarachnoid and dural sinus compartments [162]. It was thought that the tubules were
kept open by the pressure gradient of approximately
70 mm CSF between CSF and dural blood. If the
pressure differential were reversed, the tubules
would collapse and back-bleeding into the CSF
would be prevented. Electron microscopic studies [4,
1421 showed, however, that the villus is covered with
a continuous cellular membrane interspersed between the CSF and blood. This membrane would require extraordinary permeability properties to allow
particulates such as blood cells to be cleared intact
from the CSF [23]. Further studies employing the
electron microscope led Tripathi and Tripathi [ 1521
to propose that mesothelial cells of the arachnoid
villus continually form giant vacuoles capable of
transcellular bulk transport of CSF. In addition, intercellular channels through the mesothelial cap may
be sufficiently large to accommodate bulk flow [53].
The resistance to absorption of CSF in humans is
low; at a pressure of 200 mm CSF the absorption rate
climbs to three times the formation rate [28]. It follows that in the absence of other factors, an extremely high rate of formation would be required
to cause intracranial hypertension. Rarely, hydrocephalus may result from oversecretion of fluid by
a choroid plexus papilloma [37, 1031. Generally, deficits in absorption of CSF have been found in human
hydrocephalus. In some childhood cases a higher
opening pressure appeared to be required to initiate
reabsorption; in others an increased resistance to absorption was found [92]. No change in the opening
pressure has been detected in adult hydrocephalics;
instead, one study found that above a pressure of 150
mm CSF the resistance to absorption dropped sharply, to 2.5 pl/min/mm [90].In addition to absorptive
defects, CSF arterial and respiratory-induced pressure fluctuations undoubtedly play a role in ventricular
enlargement. Hydrocephalus has been produced in
2 Annals of Neurology
V o l 11 No 1 January 1982
lambs by mechanically increasing the amplitude of
the CSF pulse pressure without modifying the mean
pressure, CSF circulation, or absorption [35]. Patients with increased intracranial pressure sustain
marked tonic increases in CSF pressure (plateau
waves) with time courses varying from minutes to
hours [61,92,96], during which arterial-induced pulsations are increased in amplitude. A role for plateau
waves as a cause of hydrocephalus has been proposed
on theoretical grounds [ 148, 1491.
Three atlases of CSF cytology have been published
recently [34, 81, 1131. These illustrate that splendid
preservation of CSF cellular morphology may be
achieved through careful handling of the specimen.
Four techniques are in use for preparation of CSF cell
smears. Simple centrifugation and coverslip smears
of the sediment do not yield high-quality cytological
preparations unless the sediment is resuspended in
20% albumin to prevent drying artifacts [l50]. The
Sayk apparatus sediments cells under gentle pressure
and removes liquid by paper filtration [80]. The
cytocentrifuge provides a rapid method of handling
several CSF samples simultaneously [581; however,
cell morphology may be altered and leukocytes destroyed by centrifugation 151. Filtration through
membrane filters (Nuclepore, Millipore) is rapid and
provides the best quantitative yield of cells, but the
cytomorphology is not as well preserved as with the
sedimentation techniques [ 16,831. Gondos and King
[54] have compared the results obtained with the
Nuclepore and Millipore filters.
Cytological analysis of CSF is useful in, among
other conditions, evaluation of central nervous system tumors. The yield of positive results is generally
lower in cases of primary brian tumor (15 to 30%)
than in metastatic disease (20 to 50%) [14, 541.
Malignant cells have been found with greater frequency after surgical biopsy for resection of brain
tumors, particularly medulloblastomas, suggesting
that operation may seed malignant cells throughout
the CSF [14]. The careful studies of Glass et a1 [52],
in which CSF cytology was correlated with autopsy
findings, indicate that cells are rarely shed into the
CSF by deep parenchymal tumors. Their results
imply that the presence of such cells points to invasion of leptomeninges by the neoplasm [52]. In
Glass’s series, 60% of the patients with leptomeningeal cancer had positive cytological findings and 4% of
the series had a false-positive result, inflammatory
cells being mistaken for tumor cells. The yield of
positive cytology is enhanced by multiple examinations of the CSF [ 1 171.
Newer applications of cytological methods to the
study of CSF include characterization of B and T
lymphocytes by cell surface antigen and rosetting
techniques as a way of estimating possible immunological disorders of the nervous system. Percentages of T lymphocytes involved in cell-mediated
immunity have been reported to be higher in CSF
than in blood of patients with multiple sclerosis,
whereas the reverse has been reported for B cells
[74]. O n the other hand, a subpopulation of active T
cells containing high-affinity sheep red blood cell receptors has been found to be reduced in CSF relative
to blood of patients with multiple sclerosis. The implication of these findings is uncertain at present.
Characterization of B and T lymphocytes may also
aid in distinguishing infectious from lymphomatous
meningitis in patients with lymphomas or leukemia.
B cells predominate in lymphomatous meningitis
[55], whereas T cells are the more frequent type in
fungal meningitis 1301. A technique for identifying T
lymphocytes in CSF based on a-naphthylacetate esterase staining has recently been described [114].
Rapid diagnosis of viral encephalitis by specific immunofluorescent staining has been reported by several workers [32, 34, 85, 1211, who have demonstrated intracellular herpes simplex, mumps, measles,
and varicella-zoster viruses. These techniques deserve wider application.
Proteins, Antigens, a nd Antibodies
Most proteins in CSF normally come from blood,
their concentration in the spinal fluid being determined largely by their molecular size and the relative
impermeability of the blood-CSF barrier to large
molecules. Following the earlier studies of Kabat et a1
[73], it has become widely accepted that selective
elevation (i.e., an increased percentage) of gamma
globulin in the CSF signifies local production of the
protein within the central nervous system. Selective
elevation of CSF immunoglobulin G (IgG) has been
found in chronic infections of the nervous system,
such as syphilis or viral encephalitis, as well as multiple sclerosis, in which its measurement has proved to
be of diagnostic value. The abnormality of CSF IgG
concentration has been expressed in a variety of
ways, including the IgG/total protein ratio, the IgG/
albumin ratio, the IgG index (IgG/albumincsF/IgG/
and the IgG synthesis rate [ 15 11.
These modes of analyzing CSF IgG have been reviewed by Hershey and Trotter [65], who found the
IgG index to be most rewarding in identifying patients with definite multiple sclerosis (91%). In addition to quantitative measurement of CSF IgG, agar
gel electrophoresis and isoelectric focusing for the
identification of oligoclonal bands are useful diagnostic procedures in multiple sclerosis, increasing the
yield of identification of positive cases [65, 69, 841.
Oligoclonal bands in the CSF IgG region have been
reported in a variety of other diseases, including
myasthenia gravis [21, relapsing polyneuropathy [29],
Alzheimer disease [168], chronic encephalitis [I 531,
and meningitis [1261. Oligoconal bands of IgG have
been shown to represent specific antibodies in some
diseases, as, for example, antimeasles antibodies in
subacute sclerosing panencephalitis [ 1531 and antiCryptococcw neoformans antibodies in cryptococcal
meningitis [ 1261. In multiple sclerosis, however, it
has not proved possible to remove the CSF IgG
bands by viral adsorption.
Many studies of multiple sclerosis have demonstrated local synthesis within the central nervous
system of antibodies against a number of viruses,
including measles, rubella, vaccinia, mumps, and
herpes simplex. From a quantitative viewpoint these
antibodies account for only 5% of total CSF IgG [47,
48, 101, 111, 1541. Sensitive radioimmunoassay has
now permitted the detection of other immunoglobulin classes, including A, M, D, and E, in the CSF [105,
1091. Increased IgM has been reported to occur in
50% of patients with multiple sclerosis but in only
5% of controls [110, 1691.
Measurement of myelin basic protein in the CSF in
multiple sclerosis is gaining wide application. Two
groups have reported generally comparable findings
in large series of cases [27, 1671. In acute exacerbations of multiple sclerosis, one finds a marked rise in
immunoreactive myelin basic protein. The peak
value is achieved within the first two weeks; thereafter, the assay becomes negative or only weakly reactive. These results agree with the morphological
studies of Herndon and Kasckow [64], in which
electron microscopy of CSF sediments revealed
myelin fragments predominantly during acute exacerbations of multiple sclerosis. Myelin basic protein has been found in the CSF of patients with
acute stroke, severe hypoxia, or other demyelinating
diseases [27, 79, 1671. Proteolytic enzymes in the
CSF degrade myelin basic protein into smaller peptides which retain antigenic determinants [7, 181.
Antibodies to myelin basic protein have been found
in the CSF of patients with multiple sclerosis and
with subacute sclerosing panencephalitis [ 1191.
Biochemical Markers of Central
Nervous System Malignancy
The past two decades have produced considerable
interest in identifying and measuring tumor-related
substances in CSF to aid in the diagnosis of central nervous system tumors. In their review, Seidenfeld and Marton [141] found little value in the
measurement of various nonspecific enzymes (lactic
dehydrogenase, glutamic oxaloacetic transaminase,
aldolase, phosphohexose isomerase, lysozyme, creatine phosphokinase, isocitrate dehydrogenase, ade-
Neurological Progress: Cutler and Spertell: Cerebrospinal Fluid
nylate kinase) in the CSF. In contrast, the lysosoma1 and microsomal enzyme P-glucuronidase has
been reported to be elevated in the lumbar fluid
of the majority of patients with meningeal carcinomatosis [5, 138, 1431. The degree of elevation is
generally greater than that seen in cases of infectious
o r leukemic meningitis. Carcinoembryonic antigen, a
protein secreted by a variety of rumor cells, has also
been reported to be elevated in carcinomatous but
not infectious meningitis, and neither protein was
elevated in primary or metastatic brain tumors [ 1381.
Other markers are more tumor specific. The p
subunit of human chorionic gonadotropin (P-HCG)
is regularly elevated in the CSF of patients in whom
choriocarcinomas, gonadotropin-producing teratomas, o r germinal cell testicular carcinomas have metastasized to the nervous system [13, 1371. A
serum-CSF P-HCG ratio of less than 60 is highly
suggestive of brain metastasis, and this ratio should
be determined in all high-risk cases [13].The CSF
changes may precede clinical or radiographic evidence of metastasis, and the level of P-HCG appears
to provide a good index of tumor activity during
treatment. a-Fetoprotein, a glycoprotein produced
by yolk-sac elements, has been found to be elevated
in the CSF of patients with embryonal carcinomas; its
measurement may aid in the diagnosis of surgically
inaccessible neoplasms. The concentration of the
protein in CSF may exceed that in blood and is reported to fall during successful radiation therapy [6].
Glial fibrillary acidic protein, an astrocyte-specific
protein first purified by Eng et a1 [38],has been reported to be increased in the CSF of patients with
glial tumors, particularly glioblastomas [60]. Elevations of the polyamines putrescine and spermidine
have also been reported in malignant gliomas and
medulloblastomas, and their concentrations have
been shown to decrease during therapy [99, 1001.
More frequent measurement of these biochemical
markers may prove useful in judging the efficacy of
experimental treatment protocols.
Ions an d Metabolites
The concentration of several ions in human CSF remains nearly constant despite large fluctuations in
their plasma concentrations. Homeostatic regulation
of potassium, calcium, magnesium, and bicarbonate is
accomplished largely by choroid plexus transport
mechanisms. Brain capillaries may have an additional
role. The subject has been well reviewed by Katzman
and Pappius [77]and by Fishman [45].To date, measurement of CSF ions has had little practical application. The alterations in CSF acid-base balance that
occur during systemic acidosis or alkalosis have been
detailed by Posner and Plum [1271, Siesjo 11441, and
4 Annals of Neurology Vol 11 No 1 January 1982
Plum and Price [124]. Paradoxical changes in CSF
p H are a result of rapid equilibration of carbon
dioxide concentration and slow equilibration of hydrogen and bicarbonate ion concentration between
blood and CSF. Lactate and pyruvate concentrations
in CSF indirectly reflect the brain redox potential;
higher levels reflect an increased rate of cerebral
glycolysis [ 1451. Lactate is removed from the CSF by
a slow process resembling simple diffusion [ 1301 and
may therefore reach high levels in CSF in brain death
The concentration of glucose in CSF is clearly regulated by facilitated diffusion across membranes
comprising the blood-CSF barrier [ 2 2 , 4 4 , 1451. The
concentration of glucose in newly secreted CSF is
60% of that in plasma [164].This fraction may fall in
the presence of hyperglycemia because of saturation
of transport between blood and CSF [44].The mechanisms potentially responsible for the depression of
CSF glucose in meningitis, hemorrhage, and cancer
include increased glycolysis by adjacent neural tissue
[ 4 6 ] , utilization by granulocytes or neoplastic cells
[ 1221, and alterations in membrane transport [ 1313.
With the exception of glutamine, the concentrations of amino acids in CSF are much lower than
those in plasma. The low concentrations result from
active transport of amino acids from CSF to blood by
carrier-mediated mechanisms [88]as well as from restricted entry of amino acids from blood [49].Transport sites are found in the choroid plexus [91],
the cranial subarachnoid space [93], and the spinal
subarachnoid space [ 1081. Group-specific transport
mechanisms have been identified for large and small
neutral amino acids, diamino acids, and y-aminobutyric acid (GABA) [88]. Glutamine normally has
the same concentration in CSF and plasma. I n cases
of hepatic encephalopathy, the concentrations of
glutamine and its metabolite a-ketoglutaramate are
markedly elevated in the CSF [156].
Putative Neurotransmitters
Measurement of the CSF concentration of the
amine neurotransmitters dopamine, serotonin, and
norepinephrine, as well as their metabolic products
homovanillic acid (HVA), 5-hydroxyindoleacetic
acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol, has received wide application since
the early finding of a lowered HVA level in the
CSF of patients with Parkinson disease [20]. Because these metabolites are actively transported
out of the CSF, it is common to measure their
concentration before and after administration of
probenecid, which competitively inhibits their CSFto-blood transport [7 5, 821. After probenecid inhibition, the CSF HVA level rises in normal individuals
to a greater extent than in parkinsonian patients.
This divergence is taken to reflect a lowered brain
content and turnover of dopamine in Parkinson disease. The amines and their metabolites do not readily
cross the blood-brain barrier [l, 10, 17, 174, 1751.
Hence, it has generally been assumed that their presence and alteration in disease may be taken as a
reflection of changes in the metabolic state of the
brain, particularly of the striatum, which can discharge neurotransmitters easily into the adjacent
ventricular fluid [106]. The quantitative aspects of
the brain-CSF relationships are unknown. In fact, the
preponderance of evidence favors the spinal cord
rather than the brain as the site of origin of lumbar
CSF 5-HIAA [26, 128, 1461. There is a huge literature on the subject of amines and their metabolites in
the CSF in various neurological and psychiatric diseases. The interested reader may obtain full information in the monograph by Wood [1701. Critical
reading is important, especially of older works. As
the field has advanced, it has become clear that the
lumbar CSF concentration of amine metabolites is
influenced by age, sex, diet, drugs, state of physical
activity, diurnal rhythms, volume of the CSF sample,
and manner of storage of CSF [171]. These factors
may account for the wide range of normal values reported in the literature.
GABA among the amino acid transmitters has received the greatest attention since its presence in
CSF was first reported by Glaeser and Hare [51].
These results have been fully confirmed, and sensitive assays are now available [40, 591. GABA does
not cross the blood-CSF barrier. The CSF concentration of GABA appears to parallel its concentration in
brain [21], but there is a rostral-caudal gradient of
GABA in CSF that must be considered in clinical
studies. The concentration of GABA increases in
spinal fluid at a rate of 2% per milliliter when successive 1 ml aliquots are measured [59]. The most consistently reported abnormality in CSF GABA is its
lowering by one-half in patients with Huntington
disease [39, 981. Whether measurements of CSF
GABA will have application in the detection of
Huntington disease is unknown [98].
Cyclic nucleotides (cyclic adenosine and guanosine
monophosphate) do not cross the blood-CSF barrier,
so the CSF concentrations may also reflect activity in
the nervous system [25]. Increased levels of cyclic
adenosine monophosphate in lumbar CSF have been
reported after cerebral infarction [ 1661, migraine
[1651, and meningitis [631. Decreased levels have
been found in the ventricular fluid in prolonged coma
[ 1351. The data from animal studies are inconclusive
in showing a direct relationship between brain and
CSF cyclic nucleotides, and further work is required
before the human studies can be adequately interpreted.
Peptides, Hormones, a n d Vitamins
The neural peptides reported to be present in CSF
include thyrotropin-releasing hormone [ 1161, luteinizing hormone-releasing hormone [ 1331, somatostatin [120], substance P [112], angiotensin [123],
vasoactive intestinal polypeptide [42], gastrin and
cholecystokinin [ 1321, endorphins [68], and vasopressin [158]. An unresolved question is the role of
CSF in the delivery and distribution of these peptides
to target regions in the brain. Specialized ependymal
cells (tanycytes) bridge the median eminence of the
hypothalamus from the ventricular surface to the region of hypophyseal portal vessels. These cells may
play a role in transporting hypophysiotrophic hormones from CSF to the portal circulation [72, 1151.
Many of the peptides induce physiological actions
when injected into the cerebral ventricles [56, 116,
1611, but usually the magnitude of the endocrinological response is less and the latency greater
than when the peptides are given intravenously. Angiotensin appears to produce a more potent dipsogenic response when given by the intraventricular
route [ 1231, however, and cholecystokinin suppresses feeding in sheep only when infused into the ventricles but not when administered intravenously [33].
Intraventricular administration of P-endorphin, an
endogenous opioid peptide, produces analgesia in
humans [66]. It is also released into the ventricular
fluid of patients with chronic pain following electrical
stimulation of the medial thalamus and periaqueductal gray matter, but not of the internal capsule [3,671.
The concentration of arginine vasopressin in CSF is
not altered by changes in its concentration in plasma
[158, 1731. The levels in plasma and CSF may be
regulated by different secretory neurons. For example, in diabetes insipidus, the plasma concentration of
vasopressin falls whereas the CSF concentration remains unchanged or rises [95]. Vasopressin has been
detected in a number of hypothalamic nuclei [50],
which may release the peptide directly into the third
ventricle. The functional significance of CSF vasopressin is unknown; various proposals have been reviewed in detail by Luerssen and Robertson [94].
Whether measurement of CSF peptides will prove
useful in neurological diagnosis requires further
study [ 112, 1201.
The anterior pituitary hormones adrenocorticotropic hormone, growth hormone, thyroid-stimulating
hormone, luteinizing hormone, and follicle-stimulating hormone all have been detected in the CSF
by sensitive radioimmunoassay techniques. Under
normal conditions these hormones are probably
Neurological Progress: Cutler and Spertell: Cerebrospinal Fluid 5
derived from plasma, and their lower concentration in CSF reflects restricted entry because of their
large molecular weight. The role of the hormones
in CSF is not known. A number of studies have
shown an elevation of the CSF concentration of
growth hormone in acromegaly [ 701, of adrenocorticotropic hormone in Nelson syndrome [78], and of
prolactin in pituitary prolactinomas [7 11. In some instances, the increased hormone level in CSF may
simply reflect a corresponding elevation in plasma
level [ 11, 7 11. Most investigators agree that selective
increases in CSF concentrations of hormones (i.e.,
increased CSFlplasma ratios) are indicative of suprasellar extension of the pituitary tumor, which then
secretes hormone directly into the CSF [70, 78, 871.
In such cases measurement of CSF anterior pituitary
hormone concentrations has its greatest application.
The low-molecular-weight sex steroid hormones
estradiol, testosterone, and progesterone exist in low
concentration in CSF; the concentrations correlate
well with free (non-protein-bound) levels in plasma
[12]. CSF cortisol also reflects plasma free cortisol
[107]. There is no direct evidence that these steroid
hormones reach targets in the central nervous system
via the CSF. The pineal hormone melatonin is present in CSF [9], but, as with the pituitary hormones,
its physiological role in CSF is uncertain.
The concentration of several dietary vitamins including ascorbic acid, inositol, thiamine, and folic
acid is higher in CSF than in plasma. Transport mechanisms, principally located in the choroid plexus,
regulate the CSF concentrations of these compounds.
These control systems have been studied extensively
by Spector, Lorenzo, and their colleagues and have
been reviewed by Lorenzo [89] and Spector [147].
When radiolabeled vitamins are given to animals intravenously, their concentration rises faster in the
CSF than in subjacent cerebral cortex. These results,
as well as those from autoradiographic studies [57],
suggest that CSF is the source of brain vitamins. If
these findings are confirmed, a novel role of the CSF
as a pathway for brain nutrients would be established.
Supported by Grant NS 12079 from the US Public Health Service.
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