[Na+] of lateral ventricular cerebrospinal fluid in conscious rabbits before and after osmotic and hypovolemic stimuli

Results from direct electrode measurements of lateral ventricular cerebrospinal fluid (CSF) [Na⁺] before and after the development of water-deprived, hypovolemic, and relative cellular dehydrative thirst indicated that temporal and directional changes in CSF [Na⁺] parallel changes in plasma [Na⁺] in conscious, male rabbits. The CSF [Na⁺] of rabbits increased by 10.8 meq/liter after 48 h of water deprivation, and 7.6 meq/liter after the i.v. injection of 3 ml/kg 2 m NaCl. The CSF [Na⁺] increased immediately after the injection of hypertonic sodium and rapidly returned to control values after water gavage or voluntary water ingestion. The CSF [Na⁺] of rabbits dehydrated by the i.v. injection of 3 ml/kg 2 m sucrose and in hypovolemic rabbits (15 ml/kg 20% polyethylene glycol, s.c.) remained the same as that of controls. No change in plasma or CSF [Na⁺] occurred in rabbits injected with isotonic saline. An elevation in CSF [Na⁺] was not required for the initiation of drinking behavior in the rabbit. The data support an osmoreceptor mechanism for the development of relative cellular dehydrative thirst.     

Cholesterol ester hydrolase activity in human cerebrospinal fluid.

This study demonstrates for the first time the presence of cholesterol ester hydrolase (EC 3.1.1.13) in human cerebrospinal fluid. The pH optimum of cholesterol ester hydrolase in that fluid is approximately 6.0. The activity of the enzyme is optimal when the substrate is introduced either as an acetone solution or as a suspension in Triton X-100. Cholesterol ester hydrolase activity was not detected in human serum. It is suggested that the cholesterol ester hydrolase in cerebrospinal fluid is derived from brain and that the assay of this enzyme in cerebrospinal fluid may be of diagnostic values in various demyelinating diseases.     

Effects of mannitol and furosemide on the rate of formation of cerebrospinal fluid

The inhibitory effects of two different diuretic agents—mannitol and furosemide—on the rate of production of cerebrospinal fluid (CSF) were examined in cats by ventriculocisternal perfusion; each animal served as its own control. In 26 cats, mannitol effected as much as an 89% decrease in CSF formation as the serum osmolality was raised from 311 to 336 mosmol/liter by intravenous mannitol infused at rates from 2 to 10 mg/kg/min. The degree of decrease was a linear function of the rise in serum osmolality. Furosemide was shown to reduce CSF production by as much as 94% when intravenous doses of 0.87 to 20.3 mg/kg were used in 25 animals. The decrease was dependent on the natural logarithm of the dose. Intraventricular furosemide at concentrations of 0.06 to 0.24 mg/ml was very effective in 10 cats, without causing saluresis or diuresis. This effect was also linearly related to the natural logarithm of the concentration.     

Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pressure: experimental studies

Acute and chronic hydrocephalus was induced in lambs by mechanically increasing the amplitude of the cerebrospinal fluid (CSF) intraventricular pulse pressure without modifying the mean CSF pressure and without interfering with CSF circulation or absorption. The characteristics of the hydrocephalus so obtained, namely, the asymmetry of ventricular dilation, the dilation of the distal portions of the ventricular system, and the absence of obstructions in CSF pathways, indicated a direct role of high-amplitude intraventricular CSF pulsations in the genesis of ventricular enlargement. As no impairment in CSF circulation or absorption was induced nor variations in CSF mean pressure, this experimental model is proposed as a model for communicating hydrocephalus.     

Reproducibility of monoamine metabolite measurements in human cerebrospinal fluid

The levels of homovanillic acid (HVA), 5-hydroxy indoleacetic acid (5HIAA), and 3-methoxy-4-hydroxy phenylglycol (MHPG) were determined in the cerebrospinal fluid (CSF) of 28 patients with cognitive disorders on Day 1 and Days 8 or 15. During that period all patients were kept hospitalized under strict standard conditions, did not develop any acute CNS lesion, had no changes in their treatment and no acute systemic disease. The mean levels found in the first and second determinations were almost identical for the 3 metabolites; respectively 37.8 ng/ml and 36.3 ng/ml for HVA, 27.8 ng/ml and 27.9 ng/ml for 5HIAA, and 12.9 ng/ml and 12.3 ng/ml for MHPG. Thus, the mean values of these metabolites in CSF are reproducible at least during a 15-day hospitalization. However statistically significant individual changes in metabolite levels were found between the two samples in 82% of patients for HVA, 32% for HIAA and 48% for MHPG. The number of patients required to detect a significant change in the mean levels of each monoamine metabolite has been calculated taking into account the extent of intraindividual variations.     

Pressure-dependent bulk flow of cerebrospinal fluid into brain

Cerebrospinal fluid (CSF) absorption was studied at the cortical surface in the acutely prepared, nonhydrocephalic animal. Cerebrospinal fluid containing radioactively labeled sucrose was infused into the cisterna magna at various rates for several hours to maintain elevated cerebrospinal fluid pressures. The equilibration of sucrose in the CSF was determined by periodic supracallosal cistern sampling. The cortical sucrose distribution space was 14.2% for low infusion rates and increased to 33.9% at the high infusion rates. Apparent diffusion coefficients based on the equilibration of sucrose in the CSF were significantly higher for the intermediate and high infusion rates than for the low infusion rate group, which was the same as a supracallosal-cisternal perfusion control group. The data suggest that bulk flow of CSF across the cortical surface occurs at elevated pressures.     

Penetration of ascorbic acid from cerebrospinal fluid into brain

The penetration of [¹⁴C]ascorbic acid from cerebrospinal fluid (CSF) into brain was studied. Under pentothal anesthesia, New Zealand white rabbits were injected intraventricularly with 0.9 μCi [¹⁴C]ascorbic acid, [¹⁴C]inulin, or [¹⁴C]sucrose and 2.3 μCi [³H]mannitol. After 2 or 4 h, the rabbits were killed and the distribution of the isotopes in cerebrospinal fluid, whole brain, and 14 0.9-mm midbrain slices was measured. At 2 h, [¹⁴C]ascorbic acid penetrated the surfaces of the midbrain adjacent to the CSF to concentrations approximately two or three times more than [³H]mannitol. At 4 h, the concentration of [¹⁴C]ascorbic acid in the midbrain farthest from the CSF was also two or three times more than [³H]mannitol. These results were even more striking in view of the significantly greater decline of [¹⁴C]ascorbic acid than [³H]mannitol in the CSF with time. The direct demonstration that [¹⁴C]ascorbic acid can penetrate from the CSF into the depths of the brain substance is consistent with the view that ascorbic acid enters brain from blood primarily via the CSF.     

tau protein in cerebrospinal fluid

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230±930 pg/mL), as compared with controls (640±230 pg/mL;p<0.0001), vascular dementia, VAD (1610±840 pg/mL;p<0.05), frontal lobe dementia, FLD (1530±1000 pg/mL;p<0.05), Parkinson disease, PD (720±590 pg/mL;p<0.0001), and patients with major depression (230±130 pg/mL;p<0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.     

Morphological signs as indications of function of cells in the cerebrospinal fluid

Summary It is suggested that a continual cell exchange exists between blood and the subarachnoid space. These cells can live for a shorter or longer time there and fulfill their function depending on local conditions. In addition to phagocytosis, morphological evidence of local cellular and humoral immunological reactions have been demonstrated and how far they concour with current views on the functional state of spinal fluid cells has been examined. Peripolesis and emperipolesis, transformation of lymphocytes as well as various cell processes, as signs of function, are illustrated by light transmission and scanning electron microscopy as well as by immunological methods in various inflammatory diseases of the central nervous system.Fellow of the Bundesministerium für Wissenschaft und Forschung in the Neurological Institute of the University of Vienna (Director: Prof. Dr. F. Seitelberger).     

Butyrylcholinesterase in lumbar and ventricular cerebrospinal fluid

OBJECTIVES: This study establishes reference data for human lumbar CSF butyrylcholinesterase (E.C.3.1.1.8.) activity and investigates the enzyme activity in ventricular CSF. We comment on the relationship between CSF butyrylcholinesterase activity and other laboratory parameters. Subjects and Methods: We investigated 64 lumbar CSF samples obtained from a clinically healthy population and 169 ventricular CSF samples collected from 90 neurosurgical patients. RESULTS: The reference range we recommend for lumbar CSF butyrylcholinesterase activity is 5.4 to 17.0 nmol/min x ml. The majority of ventricular butyrylcholinesterase activities in our patient subset ranged up to 5 nmol/min x ml. CONCLUSIONS: We established the relative influence of serum and CNS components on total CSF butyrylcholinesterase activity. The CNS fraction predominates the total butyrylcholinesterase activity in normal lumbar CSF. In ventricular CSF enzyme influx from serum outweighs the CNS component.     

外伤标准大骨瓣开颅术后应用腰大池引流术的临床研究

目的探讨颅脑外伤标准大骨瓣开颅术后腰大池持续脑脊液引流术对重型颅脑损伤合并广泛性蛛网膜下腔出血的治疗效果。方法对急性重型颅脑损伤患者(GCS≤8)外伤性标准大骨瓣开颅术后,治疗组早期进行腰大池持续脑脊液引流术,对照组采用常规腰穿术,比较两组预后,分析其疗效。结果随访6个月,治疗组GOS恢复优于对照组,脑积水的发生率低于对照组。结论颅脯外伤标准大骨瓣开颅术后早期应用腰大池持续脑脊液引流术对重型颅脑损伤合并广泛性蛛网膜下腔出血患者可以提高治愈率,减少死亡率,降低脑积水的发生率,疗效好,安全性高。     

Parkinson's disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+ T cells in peripheral blood

The etiology of Parkinson's disease is mainly unknown. Immune abnormalities have been described, but the cause of such abnormalities has not been resolved. We examined by two-colour flow cytometry HLA-DR antigen expression on monocytes from cerebrospinal fluid (CSF) and blood and, moreover, lymphocyte subpopulations (CD4⁺ CD45RO⁺, CD4⁺ CD45RA⁺, CD8⁺ CD11b^+high) in peripheral blood from patients with Parkinson's disease compared with age-matched patients with other neurological diseases (OND) and tension headache. We found higher HLA-DR expression on CSF monocytes compared with blood monocytes. This difference was restricted to Parkinson's disease patients. T helper cell analysis revealed a decreased percentage of CD45RA⁺"naive" and an increased percentage of CD45RO⁺"memory" T cell subset from CD4⁺ T cells in peripheral blood of patients with Parkinson's disease compared with patients with tension headache. The proportions of CD8⁺ CD11b^+high"suppressor" T cells remained unchanged, among the three patient groups compared. A selective loss of CD4⁺ CD45RA⁺ cells, previously observed in diseases like multiple sclerosis and Down's syndrome as compared with healthy controls suggests a common immunological abnormality in neurological disorders.     

Effect of sympathomimetic drugs and corresponding receptor antagonists on the rate of cerebrospinal fluid production.

The bulk production of cerebrospinal fluid (CSF) was measured in rabbits on the basis of ventriculocisternal perfusion and dilution of [¹⁴C]inulin. Intraventricular or intravenous (i.v.) infusion of norepinephrine produced a dose-related decrease in the production by as much as 50%, the effect being counteracted by both α- and β-antagonists (except when the latter was given i.v., which potentiated the i.v. norepinephrine response). Also intraventricular (but not i.v.) administration of the β₁-receptor agonist, $\text{H80}\text{62}$, reduced CSF formation (effect blocked by practolol), in contrast to the β₂ agonist, terbutaline, which had little or no effect. It is suggested that the sympathomimetic reduction in the rate of CSF formation is the result of a combined β₁-receptor-mediated inhibition of the secretion from the plexus epithelium and a reduced blood flow in the tissue resulting from stimulation of the vascular α-receptors.     

Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate

Recent studies in sheep suggest that a significant proportion of global cerebrospinal fluid (CSF) drainage (50% or greater) occurs through the cribriform plate into nasal mucosal lymphatics. If this is true, obstructing CSF clearance through the cribriform plate should have an impact on the ability of the intracranial pressure regulating systems to compensate for volume infusions. To test this concept, bolus infusions of artificial CSF were administered into one lateral ventricle in sheep and the intracranial pressure monitored from the contralateral side. Peak intracranial pressures (ICP) were measured and CSF outflow resistances were calculated from the pressure patterns observed in response to bolus infusions administered before and after the cribriform plate was sealed in the same animal. To obstruct the cribriform plate, a portion of nasal bone was removed to expose the nasal mucosa. The olfactory mucosa, a portion of the nasal mucosa and all soft tissue on the extracranial surface of the cribriform plate were scraped away with a curette and the bone surface sealed with bone wax. Obstruction of CSF transport through the cribriform plate increased the peak ICP after infusion (P = 0.016) and augmented the time required for ICP to return to baseline. CSF outflow resistance was elevated approximately 2.7 times (P = 0.006). When the cribriform plate was left intact (sham surgery), no significant changes in peak ICP or CSF outflow resistance were observed. We conclude that the cribriform plate represents an important site for CSF clearance. Obstruction of this pathway reduces volumetric CSF transport significantly.     

Enkephalin-containing polypeptides in human cerebrospinal fluid

The chemical nature of peptides in human CSF with the enkephalin core sequence from proenkephalin A and proenkephalin B, was investigated. Direct measurements with radioimmunoassay (RIA) were run on enkephalin, enkephalin hexapeptides, dynorphin A, dynorphin A1-8 and dynorphin B. The hexapeptides occurred in about 3 times higher concentration than the corresponding enkephalins. The only dynorphin RIA which gave positive results was the one for dynorphin A. However, most dynorphin A immunoactive material showed higher apparent molecular weight (MW; 3 and 5 kdalton) than the standard (2 kdalton). To identify and quantitate every possible proenkephalin derived peptide with the enkephalin sequence, chromatographic fractions were treated with trypsin. The products, Leu-enkephalin-Arg6 (from proenkephalin B) and Met-enkephalin-Lys6/Arg6 (from proenkephalin A) were measured by specific RIAs and identified by HPLC. In the higher (greater than 5 kdalton) MW interval, there was about 10-fold higher yield of Met-enkephalyl than Leu-enkephalyl hexapeptides. In the intermediate 1-3 kdalton MW interval, most activity derived from proenkephalin B. Finally, from the low MW region, there was about 5 times more proenkephalin A peptides. The main dynorphin A peak at 5 kdalton was transferred to a major Leu-enkephalin-Arg6 peak by trypsin degradation. The data indicate the presence of a whole family of peptides from the two proenkephalin genes in human CSF. Precursors to the peptides supposed to be the active members in the proenkephalin families occur in relatively high concentrations and may provide good markers for activity in these peptide systems.     

A method for repeated sampling of cerebrospinal fluid from conscious guinea pigs

A new method is described for obtaining repeated cerebrospinal fluid (CSF) samples from conscious, unrestrained guinea pigs. A simple, disposable cannula is introduced into the cisterna magna by puncturing the atlanto-occipital membrane. The cannula is equipped with a silicone rubber disc which is glued to the membrane, forming a firm but flexible seal. Daily CSF samples of at least 100 μl can be obtained from unrestrained guinea pigs. Chronically cannulated lactating females continued to suckle their litter successfully, and their milk ejection response was not affected by withdrawal of CSF.     

Biologically active TGF-β1 is increased in cerebrospinal fluid while it is reduced in serum in multiple sclerosis patients

Objectives - The polypeptide transforming growth factor-β₁ (TGF-β₁) is a product of activated monocytes, among other inflammatory cells, and it affects immune responsiveness, cellular growth and differentiation. TGF-β₁ has potent T-cell inhibiting activities. It may play an important role in limiting autoimmune inflammation. We were interested about levels of biologically active and total TGF-β₁ in serum and CSF in patients suffering from multiple sclerosis. Subjects and methods - We measured biologically active and total TGF-β₁ in serum and CSF using ELIS A-technique in 64 MS patients with 57 during acute exacerbation of MS and 7 in remission (primary-relapsing: n=59; primary-progressive: n= 5), 20 healthy subjects, and 21 patients with other non-inflammatory neurological diseases (OND). Results - Biologically active TGF-β₁ in serum was reduced in MS patients compared to controls, on the other hand total TGF-β₁ was elevated in CSF compared to patients with OND. Biologically active TGF-β₁ in CSF correlated positively with the duration of the acute relapse in patients with primary-relapsing MS. The more relapses the patients had the higher was biologically active TGF-β₁ in CSF. Total TGF-β₁ in CSF correlated with macrophages in CSF and albumin quotient. Conclusion - We found that an elevated level of biologically active TGF-β₁ in CSF might be useful as an indicator of disease limitation while active TGF-β₁ in serum is reduced in multiple sclerosis. Measuring TGF-β₁ in body fluids by ELISA techniques produces valid results and might be used for further studies focusing on the role of this cytokine in MS.     

Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson's patients with severe postural instability and gait disorders

Summary Postural instability and gait disorders (PIGD) are the primary causes of disability in many but not all advanced Parkinson's disease (PD) patients. We have measured the concentrations of serotonin, 5-hydroxytryptophan (5-HTP), 5-hydroxy-3-indoleacetic acid (5-HIAA), and homovanillic acid (HVA) in samples of ventricular cerebrospinal fluid from ten PD patients with severe disability from PIGD and from ten PD patients with tremor and levodopa induced dyskinesia as their predominant motor dysfunction. The two groups were prospectively matched for duration of disease and age. No significant differences between the two groups were found in the concentration (mean ± SD in ng/ml, PIGD dominant vs. tremordyskinesia dominant) of 5-HIAA (106 ± 50 vs. 99 ± 34) or HVA (1,068 ± 595 vs. 881 ± 469). Serotonin concentration was significantly lower (0.7 ± 0.5 vs. 1.5 ± 0.9) and 5-HTP concentration was substantially higher (684 ± 1,054 vs. 6 ± 5) in the patient group with PIGD as their predominant symptoms. Thus, the distinguishing feature of patients with severe PIGD appears to be a derangement in indoleamine metabolism at the reaction step catalyzed by aromatic amino acid decarboxylase (AADC). These findings suggest that aggravation of PIGD in advanced Parkinson's may be related in part to impaired serotonergic transmission secondary to inhibition or down regulation of AADC.     

K+ and Na+ activation of cerebellar 5′-nucleotidase

This investigation indicates that 5′-nucleotidase activity in mouse cerebellar cortex is K⁺- and to a lesser extent, Na⁺-dependent. A possible correlation between the localization of this enzyme and neurotransmission is therefore suggested. This study also confirms a previous report that indicates that Mg²⁺ does not activate 5′-nucleotidase.