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PubMed2004

GSK-3beta in cerebrospinal fluid of schizophrenia patients.

Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970's with few definitive results. We have recently found 40% reduced protein levels of GSK-3beta in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3beta was not successful. In this study we aimed to find whether the reduction in brain GSK-3beta is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3beta protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients' postmortem brain.

Adult↗
PubMed1992

Cerebrospinal fluid neuropeptides in dementia.

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.

Aged↗
PubMed1992

Organic acids in post-mortem cerebrospinal fluid.

Organic acids of cerebrospinal fluid (CSF) have been determined by gas chromatography-mass spectrometry in 29 post-mortem samples obtained from infants and 10 samples obtained from hospitalized children, as controls. Though the organic acids profile was similar in the two groups, eight organic acids not observed in CSF from live infants were inconstantly found in post-mortem CSF and for three of them, malic acid, lactyllactic acid and uracile, concentrations were correlated with the delay in sampling.

Acids↗
PubMed1987

Morphine and codeine are endogenous components of human cerebrospinal fluid.

We have examined cerebrospinal fluid (CSF) from twelve patients who were not on any medication and found them to contain both morphine and codeine in concentrations of 2 to 339 fmol/ml. These are comparable to the concentration of opioid peptides in spinal fluid. Both morphine and codeine are present mainly in conjugated form from which the free alkaloids can be released by acid hydrolysis.

Adolescent↗
PubMed1989

Cerebrospinal fluid somatostatin in delirium.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for 67 elderly patients who met the DSM-III criteria for delirium and for 19 age-matched controls. As a group, and also when subdivided according to the type of delirium, severity of cognitive decline or the type of central nervous system disease, the delirious patients showed significant reductions of SLI compared with the controls, together with a declining trend associated with increasing cognitive dysfunction. These findings are in accordance with previous observations that reduced CSF SLI is associated with diseases in which cognitive function is disturbed and they extend this finding to delirium.

Aged↗
PubMed1982

Diaziquone, 2,5-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone, plasma and cerebrospinal fluid kinetics.

Plasma and cerebrospinal fluid (CSF) kinetics of diaziquone, 2,5-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone (AZQ), were evaluated after intravenous injection in patients with implanted Ommaya reservoirs. After a 30-min infusion plasma disappearance was very rapid, with a disposition half-life of 2 to 6 min and on elimination half-life of 25 to 35 min. Area under the concentration-time curve for CSF was 22% to 42% of the corresponding plasma area. Based upon total plasma AZQ concentration, volume of distribution for AZQ was 2.0 to 10.0 l/m2. Plasma binding of AZQ was 79% in one normal subject. When the effect of plasma binding is considered, distribution volumes are more plausible and it appears that free plasma AZQ is completely available to the CSF.

Adult↗
PubMed1990

Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis.

Cerebrospinal fluid (CSF) and serum from 45 patients with lymphocytic meningoradiculitis were examined by isoelectric focusing combined with immunoblotting to detect Borrelia burgdorferi-specific oligoclonal immunoglobulin G (IgG) bands. In pretreatment samples, 35 patients (78%) showed B. burgdorferi-specific oligoclonal IgG in CSF indicative of intrathecal antibody production. At 2, 3-6, and 6 weeks after onset, respectively, such bands were present in 5 (42%) of 12, 21 (88%) of 24, and in all of 9 patients (100%). Up to 1 year after therapy, specific oligoclonal bands in CSF tended to remain unchanged despite clinical recovery. B. burgdorferi-specific oligoclonal bands in serum were found in 7 patients. These bands had identical migration patterns as in CSF, but were fewer in number and in some patients showed a temporal evolution different from their CSF counterpart. Not all oligoclonal IgG in CSF reacted with B. burgdorferi. The 41-kDa flagellar antigen was shown to be a major antigen in the intrathecal immune response. The demonstration of B. burgdorferi-specific oligoclonal IgG in CSF is a sensitive and reliable indicator of Lyme neuroborreliosis.

Adolescent↗
PubMed1985

T-cell subsets in multiple sclerosis: relationships between peripheral blood and cerebrospinal fluid.

We contemporarily studied cerebrospinal fluid (CSF) and peripheral blood (PB) T-cell subsets, defined by monoclonal antibodies, in 29 patients with multiple sclerosis (MS) and 10 patients with other neurological diseases (OND). All subjects showed a clear-cut prevalence of CSF T-cells. Similarly, T-helper and T-suppressor subsets tended to show higher percentages in CSF in almost all subjects except relapsing MS, who were characterized by low percentages of T-suppressors in PB and even much lower percentages in CSF. Helper/suppressor ratios were found to be almost similar in the two body compartments of OND patients, lower in CSF than in PB of chronic progressive MS, always higher in CSF than in PB of relapsing MS. MS patients in remission showed both patterns of progressive MS and OND patients. Our results demonstrate that the loss of PB T-suppressor in relapsing MS is not due to a migration of such cells into CSF. Furthermore, regarding T-lymphocyte subsets, a typical CSF/PB pattern characterizes relapsing MS from other patients.

Adult↗
PubMed1994

A long-term follow-up study of cerebrospinal fluid somatostatin in delirium.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for elderly delirious patients during the acute stage and after 1- and 4-year follow-up periods, and the SLI levels were compared with age-equivalent controls. As a whole group, and also when the group was subdivided according to the severity of cognitive decline at the acute stage, type of delirium or the central nervous system disease, delirious patients showed significant reduction of SLI as compared with the controls. In the follow-up, we observed a further reduction of CSF SLI together with significant correlations in the second, third and fourth samples between SLI levels and Mini-Mental State Examination scores. Our results suggest a role for somatostatinergic dysfunction in the genesis of some symptoms of delirium, and this dysfunction may be linked to the long-term prognosis of delirious patients.

Aged↗
PubMed1986

Aminergic studies and cerebrospinal fluid cations in suicide.

Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) measurements have been collected over six years from 275 drug-free, recently hospitalized psychiatric patients, almost exclusively females. In accord with other observations from various countries, patients who had attempted suicide shortly before admission had significantly lower mean CSF 5-HIAA concentration and this was particularly true for those using violent methods. This finding could be replicated in five subsequent samples of patients evaluated separately and using different assay procedures, and proved to be independent of the clinical diagnoses. CSF HVA also showed similar tendencies but it had much larger variance with respect to suicide attempts and therefore fell short of statistical significance. In two patient populations CSF calcium and magnesium measurements have been obtained. CSF calcium did not prove to be related to either suicidal behavior or the diagnosis of major depression; on the other hand, CSF magnesium was found to be significantly lower in the suicide attempters and also correlated with CSF 5-HIAA. Nonsuicidal depressives had comparable CSF calcium and magnesium levels to the controls.

Adult↗
PubMed1992

Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys.

Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.

Animals↗
PubMed1991

Evidence for the existence of serotonin uptake inhibitor-like substances in human cerebrospinal fluid.

Addition of human cerebrospinal fluid (CSF) induced a marked inhibition of 3H-paroxetine binding to the monkey cortical membranes, while the specific binding of 3H-imipramine was slightly inhibited. Moreover, 3H-serotonin (5-hydroxy-tryptamine, 5-HT) uptake inhibition in the monkey cortical synaptosomes was also increased as the volume of added CSF was increased. Scatchard analysis of specific 3H-paroxetine binding with human CSF showed non-competitive kinetics, although CSF was competitive with 3H-imipramine binding. The inhibitory effect of human CSF on 5-HT uptake was non-competitive in nature. The endogenous substances in human CSF most probably act at the recognition site labeled with 3H-paroxetine. Moreover, occupation of this site by the endogenous substances is likely to inhibit the 5-HT uptake process.

Animals↗
PubMedDate not supplied

Pineal vasotocin: REM sleep dependent release into cerebrospinal fluid of man.

Lumbar cerebrospinal fluid (CSF) of seven healthy male volunteers contains detectable levels of arginine vasotocin (AVT) when CSF was removed after awakening from rapid eye movement (REM) sleep. No detectable levels of AVT were found in the CSF of the same subjects when CSF WAS removed after awakening from non rapid eye movement (NREM) sleep. The amount of AVT detected in CSF after REM sleep was significantly higher if the subjects experienced vivid and emotive dreams. The present results provide the first evidence for a REM sleep dependent release of AVT into CSF of man.

Adult↗
PubMed1989

[Intrathecal immunoactivation in the patients with myasthenia gravis--autoantibodies in the cerebrospinal fluid].

We examined the cerebrospinal fluid (CSF) of 17 myasthenia gravis (MG) patients for certain immunological parameters in order to assess signs of intrathecal immunoactivation. We have found oligoclonal IgG bands in the CSF of 6 of 17 by the agarose gel electrophoresis and enlarged lymphoid cells in CSF of 8 of 17 patients of MG. We measured anti-nicotinic acetylcholine receptor (AChR) antibody and anti-striational muscle antibody (AMA) in serum and CSF from MG patients and compared the serum: CSF ratio with total IgG. No evidence of intrathecal anti-AChR antibody synthesis was demonstrated while AMA was partly (50%) synthesized in myasthenic CSF. This difference suggested that there is either different immunological regulation in synthesis between anti-AChR antibody and AMA in the CSF or the different behavior after transfer to CSF.

Adult↗
PubMed1987

[Diagnostic significance of detecting respiratory virus antigens in cerebrospinal fluid and brain cells].

Cerebrospinal fluid (CSF) from 202 patients (114 children and 88 adults) was studied by immunofluorescent techniques. Antigens of respiratory viruses in the CSF were most frequently encountered (22%) in patients with the involvement of the central nervous system (usually meningoencephalitis) in the presence of acute respiratory disease. In lethal outcomes in the same group viral antigens in brain cells were also identified. Clinical and morphological findings suggest that these lesions are infectious-allergic in nature. In rare cases (4%) viral antigens in the CSF and brain cells may also be found in patients with acute respiratory diseases without central nervous system involvement which happens when patients' blood-brain barrier is especially permeable.

Adult↗
PubMed1978

Probenecid inhibition of methotrexate-cerebrospinal fluid pharmacokinetics in dogs.

Cerebrospinal fluid (CSF) and plasma concentrations of methotrexate (MTX) were followed in dogs for 72 hours after intracisternal injection of MTX with and without probenecid pretreatment. CSF levels declined as a biexponential function of time. Probenecid pretreatment of the animals prolonged the second phase half-disappearance time of MTX from 5.20 +/- 0.89 to 7.086 +/- 0.23 hours (mean +/- SD). The peak mean plasma concentration of MTX was lower in the presence of probenecid. Also, the rate of decline of plasma MTX concentrations was slower after treatment with probenecid, with mean half-disappearance times of 7.60 +/- 0.77 and 11.32 +/- 1.08 hours. These CSF and plasma data support the proposal that probenecid inhibits the transfer of MTX from CSF to blood.

Animals↗
PubMedDate not supplied

The partitioning of cimetidine into canine cerebrospinal fluid.

The pharmacokinetics and cerebrospinal fluid (CSF) partitioning of cimetidine were studied in the dog. Four healthy male mongrel dogs were given a 22 mg/kg iv dose of cimetidine. The dogs demonstrated metabolic and pharmacokinetic characteristics similar to human volunteers, as the total body clearance of cimetidine averaged 7.5 ml/min/kg in the dog as compared to 7.7 ml/min/kg in humans. Autopsy tissue concentrations were similar to those measured in humans. There were no statistical differences between dogs and humans in any pharmacokinetic parameters. Cimetidine sulfoxide was the major metabolite in the dog, similar to that in humans. Cimetidine CSF partitioning, as determined by the ratio of cimetidine CSF:serum area under the curve was 0.125 +/- 0.03. Cimetidine appears to enter the CSF by passive diffusion, and is removed by passive diffusion, CSF bulk flow, and possibly by an active transport process. We conclude that the dog is an appropriate animal to investigate cimetidine pharmacokinetics and is a suitable model for examining the CSF uptake of H2-antagonists.

Animals↗
PubMed1980

Active transport of methotrexate from cerebrospinal fluid in humans.

The cerebrospinal fluid (CSF) efflux kinetics of methotrexate (MTX) were studied in three patients with indwelling Ommaya reservoirs. A small dose of MTX was injected intraventricularly several hr after the start of a high-dose continuous i.v. infusion of MTX. In all patients, the CSF antifolate concentration returned to the preinjection level before the end of the i.v. infusion. This result indicated that the efflux of MTX from CSF in humans is independent of plasma drug concentrations. Efflux kinetics were further characterized in one patient. Serially obtained CSF samples after intraventricular injections demonstrated a biphasic disappearance curve with alpha- and beta-phase half-disappearance times of 1.7 and 6.6 hr, respectively. Prolongation of the beta-phase half-time was associated with oral acetazolamide medication and with increased intracranial pressure, indicating that inhibition of CSF production slows MTX clearance. CSF MTX concentration, however, declined more rapidly than that of simultaneously administered diethylenetriaminepentaacetic acid, an extracellular marker substance excreted by bulk flow, indicating that bulk flow excretion alone is insufficient to account for MTX efflux from human CSF. Evidence that there is an active transport component was provided by probenecid pretreatment which also prolonged the CSF MTX half-life. These findings suggest that both passive and active mechanisms govern MTX efflux from the CSF in humans and that they can be inhibited by acetazolamide and probenecid, respectively.

Acetazolamide↗