Evaluation of the usefulness of the ELISA method for determining the level of enterovirus antibodies in serum and cerebrospinal fluid

The usefulness of the methods was compared: complement fixation test (CFT), neutralization test (NT) and ELISA IgG and IgM against enteroviruses for the evaluation of specific immune reaction in sera and cerebrospinal fluid (CSF) samples of patients with confirmed enterovirus infections. The criteria were established for the assessment of ELISA results in rapid diagnosis of enterovirus neuroinfections. The criteria accepted by the producer lowered the sensitivity of the method and the possibility of recognition of local synthesis of antibodies in the CNS. The use of serum negative in CFT and negative CSF as reference for the determination made possible using of that kit for rapid diagnosis of neuroinfections. The modified ELISA IgG test makes possible determination of antibodies in CSF and serum, and accepting the generally recognized criteria for local production of antibodies in the CNS the ELISA test makes possible rapid diagnosis of neuroinfections which is not possible by other methods.     

Leukotrienes increase levels of prostanoids in cerebrospinal fluid in piglets

We investigated effects of exogenous leukotrienes (C4, D4, or E4) on levels of prostanoids in cerebrospinal fluid in newborn pigs (1-5 days). A "closed" cranial window was placed over the parietal cortex. Pial arterial diameter was measured with a microscope and electronic micrometer system. Levels in cerebrospinal fluid (CSF) of 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha), Thromboxane B2 (TXB2), and Prostaglandin E2 (PGE2) were measured by radioimmunoassay. Topical application of leukotrienes C4, D4, or E4 (5,000 ng/ml) similarly constricted pial arteries by 15 +/- 2% (n = 14) (mean +/- SEM). In addition, leukotrienes increased levels of 6-keto-PGF1 alpha from 806 +/- 136 to 1,612 +/- 304 pg/ml (n = 13), TXB2 from 161 +/- 31 to 392 +/- 81 pg/ml (n = 10), and PGE2 from 2,271 +/- 342 to 4,636 +/- 740 pg/ml (n = 13). Each type of leukotriene had similar effects on prostanoid synthesis. In other experiments (n = 5), we found that 2.0 ng/ml PGE2 in CSF dilated pial arteries by 24 +/- 8% and that 1.0 ng/ml PGI2 dilated pial arteries by 15 +/- 6%. These results indicate that leukotrienes are able to increase levels of prostanoids in cerebral cortex.     

24-hour cerebrospinal fluid levels of vasopressin in hydrocephalic patients

The variation in vasopressin concentrations of ventricular cerebrospinal fluid and plasma throughout a 24-h period was studied in 10 patients with hydrocephalus. In 6 control patients, the diurnal variation in plasma vasopressin concentrations was studied. Vasopressin concentrations were determined by radioimmunoassay in plasma and in extracted and unextracted cerebrospinal fluid. Cortisol and osmolality in plasma were also measured. Vasopressin concentrations measured in extracted cerebrospinal fluid showed only small intra- and interindividual variation, while the corresponding values for unextracted cerebrospinal fluid were 2-5-fold higher and showed more variation. Plasma vasopressin concentrations varied considerably throughout the 24-h period in the individual hydrocephalic patient and between the patients. The pattern of variation was inconstant with no circadian rhythm, and the variation was not related to any changes in plasma osmolality, blood pressure or intracranial pressure. In some of the patients, the normal diurnal pattern of variation in plasma cortisol was broken, however, without a relation to the observed fluctuations in vasopressin concentrations. The abnormal variation of plasma vasopressin and cortisol was considered to reflect stress in connection with the intracranial pressure monitoring procedure. In the control patients, plasma vasopressin showed only small variations and plasma cortisol showed a normal diurnal rhythm. It is concluded that cerebrospinal fluid vasopressin concentration in patients with hydrocephalus is very constant throughout the day, even when plasma vasopressin concentrations show marked episodic increases. Thus, a circadian rhythm in the cerebrospinal fluid vasopressin concentration, as reported in several animal species, could not be confirmed in these patients.     

Estimation of C3 levels in cerebrospinal fluid by electroimmunodiffusion

C3 levels have been determined by the electroimmunodiffusion technique in the CSF of patients with a wide variety of pathologies. The patients were grouped on the basis of protein content and G/A ratio of the CSF as I) patients with normal meningeal permeability and apparent absence of local gamma-globulin synthesis; II) patients with increased meningeal permeability; III) patients with characteristics of MS, i.e. increase of IgG accompanied by a normal or slightly elevated protein content, Group III showed a lower level of C3 when expressed at % of the total protein and also as % of the total protein less gamma-globulins of the CSF. Other parameters of the CSF are also recorded. It was shown that only the expression of C3 concentration relative to the total protein content of the CSF produced meaningful analytical data.     

Evaluation of postmortem serum and cerebrospinal fluid growth hormone levels in relation to the cause of death in forensic autopsy

Previous studies have shown that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly lower in cases of asphyxia and poisoning than in other groups, whereas ACTH levels in cerebrospinal fluid (CSF) were significantly lower for hypothermia and hyperthermia. This study comparatively analyzed growth hormone (GH) levels in serum and CSF in relation to cause of death in routine forensic work. Autopsy cases (n?=?116), including cases of blunt injury, sharp instrument injury, fire fatality, asphyxia, drowning, hypothermia, and acute myocardial infarction/ischemia (AMI), were examined. GH concentrations were measured using an immunoradiometric assay technique. GH levels in serum were significantly higher in cases of blunt injury, sharp instrument injury, hypothermia, and AMI than in the other groups. GH levels in CSF were significantly higher in fire fatality cases with a high COHb level than in the other groups. In a previous study ACTH immunopositivity in the adenohypophysis was significantly higher in cases of blunt injury, fire fatality, and AMI whereas GH immunopositivity was not significantly different among the groups, although positivity was higher in cases of fire fatality with a low COHb level. These observations suggest that postmortem serum/CSF GH and ACTH levels in acute deaths change differently, depending on the cause of death, because of varied stress reactions of the hypothalamic-pituitary-adrenal (HPA) axis.     

In vivo influences on cerebrospinal fluid amino acid levels

The concentration of 19 amino acids and ethanolamine in two independent groups (n = 36, n = 19) of normal human cerebrospinal fluid (CSF) samples were measured by high performance liquid chromatography. Age, sex, time of lumbar puncture, position during lumbar puncture, protein and glucose content of the CSF were monitored and the influence of these parameters on CSF amino acid levels was determined. Hypotheses formulated after observing measurements from the first group of CSF samples were tested against the second group of CSF samples using conservative statistics. The main finding was a positive correlation between CSF glucose and CSF glutamate levels.     

Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms

Background

Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1) in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs).

Results

In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r² = 0.93, p < 0.01). In contrast, CSF apoE levels in different individuals varied widely (coefficient of variation = 46%). CSF apoE levels did not vary according to AD status, APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r² = 0.05, p = 0.003). We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported.

Conclusion

We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.     

TOMM40 poly-T variants and cerebrospinal fluid amyloid beta levels in the elderly

A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer’s disease in APOE ε3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, in cognitively intact elderly subjects. APOE ε4 carriers showed significant reductions in Aβ 1-42 levels compared to non-ε4 carriers, but no differences were detected across TOMM40 variants. Neither Aβ 1-40 nor tau levels were affected by APOE or TOMM40.     

Clonidine reduces elevated cerebrospinal fluid catecholamine levels in patients with essential hypertension

Cerebrospinal fluid (CSF) catecholamines were measured in normotensive patients and in patients with mild to moderate essential hypertension. CSF-norepinephrine (NE) concentrations were 50% lower in the normotensive individuals (127 ± 28 vs. 240 ± 23 pg/m1) (P<0.01). In hypertensive patients, CSF-NE was inversely related to age (r =-0.68; P<0.01) and directly related to plasma NE (r = 0.61; P<0.05). Clonidine (450 mcg/day for 2 weeks) significantly reduced CSF-NE (?40%) in hypertensive patients. In addition, it decreased blood pressure, plasma and urinary NE. Urinary VMA was not affected by clonidine. No correlation was observed between clonidine effects on BP and on plasma or CSF catecholamines. This study indicates that patients with essential hypertension have elevated levels of CSF-NE which are reduced after treatment with clonidine. The elevation of CSF-NE suggests that central (spinal?) noradrenergic activity may be increased in patients with mild to moderate essential hypertension, and that can be reduced by treatment with clonidine.     

Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic encephalopathy

Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for alpha-tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier.