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The function of the cerebrospinal fluid space and its expansion.

In addition to its nutritive and protective effects, the basic function of the cerebrospinal fluid space resides in dynamic equilibration of pressure fluctuations caused by volume changes in three compartments contained within the rigid skull cavity: brain tissue, blood and cerebrospinal fluid. An increase in volume in one of them brings about a compliant withdrawal in volume in the other two. The degree of cerebrospinal fluid compliance can be expressed by means of the pressure/volume index which is directly proportional to this compliance. On the other hand an expansion of fluid space which forces the brain to withdraw its tissue, brings about the dilatation of brain ventricles. The degree of their dilatation depends on the effective pressure of cerebrospinal fluid which counteracts with the resistance of brain venous collectors. The blood in the venous network of the brain and cerebral extracellular fluid play a reversible role in cerebral mass restoration and reduction. These facts explain the reason why, from the physical point of view, the brain is considered to represent a viscous and elastic spongious matter. (Ref. 21.)

Absorption↗

Evidence for transforming growth factor-beta expression in human leptomeningeal cells and transforming growth factor-beta-like activity in human cerebrospinal fluid.

BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-beta (TGF beta) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGF beta isoforms TGF beta 1, TGF beta 2, and TGF beta 3 as well as TGF beta-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGF beta 1, TGF beta 2, and TGF beta 3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGF beta-like activity. RESULTS: Transcripts for TGF beta 1, TGF beta 2 and TGF beta 3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGF beta 1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGF beta 2 and TGF beta 3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGF beta 1 and extensive TGF beta 2 and TGF beta 3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGF beta-like activity. TGF beta radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGF beta-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TG beta-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGF beta 1, TGF beta 2 and TGF beta 3 and secrete latent TGF beta s at least in vitro. Human cerebrospinal fluid may also contain TGF beta isoforms. Collectively, these observations raise the possibility that members of the TGF beta family contribute to biologic processes of the leptomeninges.

Agar↗

Metabolite profile of cerebrospinal fluid in patients with spina bifida: a proton magnetic resonance spectroscopy study.

STUDY DESIGN: The present study was carried out to assess the metabolic differences between cerebrospinal fluid samples of patients with spina bifida and age-matched control individuals. OBJECTIVES: To study the metabolite profile of cerebrospinal fluid of patients with spina bifida using proton magnetic resonance spectroscopy, compare the levels of metabolites with controls, establish correlation of underlying neuronal dysfunction with metabolic changes in patients with spina bifida, and evaluate the potential use of this technique as an additional tool for diagnostic assessment. SUMMARY OF BACKGROUND DATA: Combination of embryopathy, stretching, ischemia, compression, and trauma is responsible for cord dysfunction in spina bifida. Changes in neuronal metabolism leads to changes in the local milieu of cerebrospinal fluid in the cord. Change in metabolite profile of cerebrospinal fluid in spina bifida in terms of increase in products of anaerobic metabolism, nerve membrane integrity, and nerve ischemia has not yet been studied. METHODS: Cerebrospinal fluid obtained from patients and control individuals were characterized using various one- and two-dimensional proton magnetic resonance spectroscopy techniques. Concentration of various metabolites was calculated using the area under the nuclear magnetic resonance peak. RESULTS: Statistically significantly higher levels of lactate, choline, glycerophosphocholine, acetate, and alanine in the cerebrospinal fluid of patients with spina bifida was observed compared with control individuals. CONCLUSIONS: Significantly higher levels of metabolites were observed in patients with spina bifida, representing a state of nerve ischemia, anaerobic metabolism, and disruption of neuronal membrane.

Acetates↗

Onset of uncomplicated cerebrospinal fluid fistula 27 years after head injury: case report.

BACKGROUND: Cerebrospinal fluid fistulae complicated by meningitis have been reported to appear as late as 36 years after the causal head injury. METHODS: We present this 54-year-old woman with a recurrent cerebrospinal fluid rhinorrhea that started 27 years after a road accident. The surgical exploration revealed a linear fracture of the cribriform plate. RESULTS: Once the defect was repaired, the leak ceased, with no recurrence in 2 years of follow-up. CONCLUSIONS: A traumatic cerebrospinal fluid leak may appear for the first time after 2-3 decades have elapsed. An operation is indicated in order to localize the site of leakage, when other investigations have failed or are not available, as well as to prevent a secondary infection, when still possible.

Cerebrospinal Fluid Rhinorrhea↗

Analysis of bacterial isolates from cerebrospinal fluid.

We set out to determine the frequency of occurrence of contamination of cerebrospinal fluid with bacteria, seeking also to identify aids to differentiating contaminants from etiologically significant isolates. From 2,091 specimens, 182 bacterial isolates were obtained from 129 patients. Meningitis was the source of 81 isolates (32 patients); contamination yielded 101 isolates (97 patients). The cell counts and protein and glucose concentrations in the cerebrospinal fluid were significantly more often abnormal in specimens from patients with meningitis. Haemophilus influenzae and enteric gram-negative bacilli were usually cause for meningitis, whereas Staphylococcus epidermidis was the most common contaminant. In view of the reported high rate of procedural error in carrying out lumbar puncture, a program aimed at teaching proper technique is recommended to decrease the frequency of false-positive cultures of cerebrospinal fluid.

Bacteria↗

Bilirubin excess, erythrophages and siderophages in differentiation of blood in cerebrospinal fluid.

Non-artificial blood admixture in cerebrospinal fluid (CSF) can be proven by demonstrating siderophages and 'bilirubin excess'. Bilirubin excess exists when the bilirubin concentration measured in the CSF exceeds the expected CSF bilirubin concentration. The expected CSF bilirubin concentration is calculated by multiplying the serum bilirubin concentration by the albumin quotient. Given a certain method of determination, a difference between the above-mentioned concentrations of less than 0.15 mumol/l must not be regarded as excess. Bilirubin excess was exclusively found in CSF with non-artificial blood admixture. Cytological and spectrophotometric studies are sufficient in screening for non-artificial blood admixture. When there are indications of an increased bilirubin concentration, calculations should be made in order to establish whether bilirubin excess exists. Lumbar puncture within 48 hours of the suspected haemorrhage should be avoided if possible.

Bilirubin↗

[Cerebrospinal fluid in the diagnosis of spinal schistosomiasis].

Cerebrospinal fluid (CSF) changes in spinal schistosomiasis have been described. Its characteristic features are mild to moderate pleocytosis, presence of eosinophils, slight to moderate protein increase, elevated gamma globulin concentration and a positive immune assay. Nevertheless, these abnormalities are not always present together and therefore difficulties may arise in the assessment of the diagnosis. The purpose of this paper is to evaluate the importance of each CSF alteration concerning the diagnosis in 22 cases of spinal schistosomiasis. According to the results, only 20% of the cases had all the five feature that are considered to be characteristic of spinal schistosomiasis. Abnormal cell count was present in 86%, protein increase in 77.3%, immunoglobulin G increase in 60,8%, eosinophils were present in 36.8% and indirect fluorescent antibody test was positive in 68.2%. In three cases all CSF parameters studied were within the normal limits. As the most specific test among those described was the indirect fluorescent antibody test, it should be regarded for the diagnosis.

Adolescent↗

Cerebrospinal fluid cell count following spinal cord injury.

Cerebrospinal fluid (CSF) changes after spinal cord injury (SCI) were evaulated by retrospective analysis of all patients admitted to the Acute Spinal Cord Injury Unit (ASCIU) at University Hospital, Shaughnessy Site in Vancouver, British Columbia. A total of 1,917 admissions occurred during the 10-year study period with 1,151 due to acute trauma. The charts of all patients with SCI due to trauma were reviewed to identify patients in whom a CSF puncture was performed for any reason. Traumatic SCI is associated with elevations in the corrected white blood cell count (cWBC) that we believe reflect an inflammatory response to injury. The elevation in cWBC is greatest in the first week after injury. Elevations in cWBC more than 1 week after injury do occur but are uncommon. The white cell differential count consists primarily of lymphocytes and polymorphonucleocytes. Three weeks after injury cell counts should be normal. Protein levels are elevated after trauma and should not be used to assess the presence of infection. LP should be part of the septic workup of SCI patients just as it would be for any other population if meningitis is a consideration.

Adolescent↗

[Sulfalene kinetics in the blood and cerebrospinal fluid in arachnoiditis].

The kinetics of free sulfalene in the blood and cerebrospinal fluid was studied in patients suffering from chronic arachnoiditis without marked inflammation signs on the part of arachnoid after a single intake of 2 g of the drug. It was found that administration of the drug in this dose once a week is quite justified and that sulfalene penetrates well in the cerebrospinal fluid. Upon administering large doses of the drug its absorption from the gastrointestinal tract declines. Sulfalene is eliminated from the cerebrospinal fluid more slowly than from the blood. High enough drug concentration is maintained in the cerebrospinal fluid for 7 days.

Adolescent↗

Isolation and characterisation of an anticryptococcal protein in human cerebrospinal fluid.

An earlier study reported that human cerebrospinal fluid (CSF) has fungistatic activity for Cryptococcus neoformans. The present study reports that molecular sieve fractionation of concentrated CSF yielded three protein peaks, one of which (p2) had anticryptococcal activity. On a DEAE-Sephacel anion-exchange column the active molecular sieve peak (p2) gave two peaks that contained anticryptococcal activity. The first (DEAE-1) eluted with 0.1 M NaCl and the second (DEAE-2) eluted with 0.2 M NaCl in buffer. Fungistatic activity of DEAE-1 was reversed by FeCl3. Moreover, FeCl3 reversed inhibition of C. neoformans growth by CSF. In contrast, activity of DEAE-2 was not reversed by FeCl3, indicating that inhibition was produced by an iron-independent mechanism. Immunoblot assays showed that transferrin was present in DEAE-1 but not in DEAE-2, whereas albumin was present in DEAE-2 but not in DEAE-1. On NuPAGE, DEAE-1 protein migrated as a single band corresponding to transferrin and DEAE-2 protein gave a single band corresponding to albumin. In control experiments, human serum albumin subjected to the same isolation protocol acquired anticryptococcal activity similar to that of DEAE-2. Therefore, CSF albumin (DEAE-2) activity was associated with the isolation protocol. These data indicate that transferrin, present in or isolated from CSF, sequesters trace amounts of ferric iron, inhibits growth of C. neoformans and acts as an innate defence mechanism.

Cerebrospinal Fluid↗

The influence of electrical stimulation of certain brain regions on the concentration of acetylcholinesterase in rabbit cerebrospinal fluid.

Electrical stimulation of either the caudate nucleus, substantia nigra or lateral hypothalamus led to an increase in the concentration of acetylcholinesterase in cerebrospinal fluid collected from the cisterna magna of the rabbit. This effect was not due to gross cell damage, fluid loss or contamination with blood plasma. Cerebrospinal fluid collected from the lateral ventricle contained a lower concentration of acetylcholinesterase than that collected from the cisterna magna; furthermore, stimulation of the ipsilateral caudate nucleus caused no change in the concentration of this enzyme in ventricular cerebrospinal fluid. After placing a large lesion in the ipsilateral substantia nigra, the 'resting' concentration of acetylcholinesterase in cisternal cerebrospinal fluid was 43% of the value in unoperated rabbits and stimulation of the caudate nucleus no longer led to an increase in the concentration of acetylcholinesterase in cisternal cerebrospinal fluid. The possibility is discussed that when the caudate nucleus is stimulated, acetylcholinesterase is released from the substantia nigra.

Acetylcholinesterase↗

Aluminum and gallium arrest formation of cerebrospinal fluid by the mechanism of OH- depletion.

AlCl3 or GaCl3 was added to artificial cerebrospinal fluid and perfused through the cerebral ventricles of the rat. Depending on the metal and its concentration (1-10 mM) the pH of the perfusate ranged from 7.2 to 3.5. At 10 mM metal chloride, yielding pH 4.7 (Al) or 3.5 (Ga), formation of cerebrospinal fluid was suppressed 100%. The effect was reversed as soon as control cerebrospinal fluid (pH 7.35) was introduced. There was no effect at pH greater than 6 in the presence of metal ions nor was the effect mimicked by cerebrospinal fluid acidified with HCl or phosphate buffer to pH 4.7. HCl and phosphate at pH 4.7 had partial effects (25-30%). Inhibition of carbonic anhydrase is well known to have a partial effect (approximately 50%), the remainder of normal flow being dependent on the uncatalyzed formation of HCO3- and the corresponding movement of Na+. The complete cessation of flow after exposure to Al or Ga ions appears to occur when these ions are perfused at pH where they are partly hydrolyzed. Under these circumstances they form very powerful proton generating systems (as shown by titration data), which could lower [OH-] at the secretory border of choroid plexus cells. As a result, both the catalyzed and the uncatalyzed processes for formation of HCO3- from CO2 are abolished and secretion stops. This mechanism may also account for the antiperspirant action of Al salts. Using metal ion hydrolysis to probe other secretory systems will also be of interest.

Acetazolamide↗

Integrating the roles of extracranial lymphatics and intracranial veins in cerebrospinal fluid absorption in sheep.

At relatively low cerebrospinal fluid (CSF) pressures, the majority of CSF drainage in 6- to 8-month-old sheep occurs through the cribriform plate into lymphatic vessels in the nasal submucosa. As CSF pressures are elevated, other absorption sites are recruited and these may include transport through arachnoid projections. To test for the transport of CSF directly into the venous sinus, the concentration of a tracer (131I-human serum albumin [HSA]) administered into the CSF compartment was measured in the confluence of the intracranial venous sinuses (torcular) and in the peripheral blood (inferior vena cava). CSF pressures were adjusted to favor absorption. Enrichment of the CSF tracer in the cranial venous system was most evident when the CSF-venous sinus pressure gradients were high. Peak concentration differences occurred 90 s after the CSF pressures were elevated. When pressure gradients approached 30 cm H(2)O, tracer concentrations in the torcular were approximately twofold higher than those observed in peripheral blood. The greatest concentration differences favoring the torcular were obtained when the CSF-venous sinus pressure gradients were elevated to high levels (20- to 40 cm H(2)O) and when CSF access to the paranasal lymphatics and CSF transport into the spinal subarachnoid compartment were prevented. In conjunction with previous studies, these results are compatible with the view that CSF absorption in the adult animal can occur directly into the cranial venous system. However, contrary to the established view, this pathway may represent a secondary system that is recruited to compliment lymphatic transport when global absorption capacity is stressed or compromised.

Absorption↗

[Diagnosis of cerebrospinal fluid leakage at the base of the skull].

There are still several problems surrounding the diagnosis of cerebrospinal fluid leak. Currently the method of choice for cerebrospinal fluid detection is qualitative determination of beta-2-transferrin. Faster and more efficient methods (beta-trace) are under clinical investigation. The major problem is localisation of the site of leakage. Combination of several radiological methods increases the rate of correct diagnosis. In surgery the use of intrathecal sodium-fluorescein improves visualisation of the site of leakage and thus increases the chances of secure and stable closure of the cerebrospinal fluid fistula.

Cerebrospinal Fluid↗

Non-traumatic cerebrospinal fluid rhinorrhea indirectly caused by remote brain tumor: a case report and review of the literature.

Non-traumatic cerebrospinal fluid rhinorrhea indirectly caused by a remote brain tumor has rarely been reported. Here we describe a case of non-traumatic cerebrospinal fluid rhinorrhea that occurred as the initial symptom of a posterior falx meningioma. In addition, based on the period of occurrence of cerebrospinal fluid rhinorrhea before or after the tumor operation, we introduced a novel classification for these cases into pre-treatment and post-treatment types. The findings of the present case and the results of our literature research suggest that different treatments should be used for patients with these two types of non-traumatic cerebrospinal fluid rhinorrhea resulting from remote brain tumor. After tumor excision, patients of the pre-treatment type may receive conservative management or cerebrospinal fluid shunting, while patients of the post-treatment type need direct repair of the fistula.

Adult↗

Impairment of blood-cerebrospinal fluid barrier properties by retrovirus-activated T lymphocytes: reduction in cerebrospinal fluid-to-blood efflux of prostaglandin E2.

The choroid plexus epithelium forms the interface between the blood and the CSF. In conjunction with the tight junctions restricting the paracellular pathway, polarized specific transport systems in the choroidal epithelium allow a fine regulation of CSF-borne biologically active mediators. The highly vascularized stroma delimited by the choroidal epithelium can be a reservoir for retrovirus-infected or activated immune cells. In this work, new insight in the implication of the blood-CSF barrier in neuroinfectious and inflammatory diseases is provided by using a differentiated cellular model of the choroidal epithelium, exposed to infected T lymphocytes. We demonstrate that T cells activated by a retroviral infection, but not non-infected cells, reduce the transporter-mediated CSF-to-blood efflux of organic anions, in particular that of the potent pro-inflammatory prostaglandin PGE2, via the release of soluble factors. A moderate alteration of the paracellular permeability also occurs. We identified the viral protein Tax, oxygenated free radicals, matrix-metalloproteinases and pro-inflammatory cytokines as active molecules released during the exposure of the epithelium to infected T cells. Among them, tumour necrosis factor and interleukin 1 are directly involved in the mechanism underlying the decrease in some choroidal organic anion efflux. Given the strong involvement of CSF-borne PGE2 in sickness behaviour syndrome, these data suggest that the blood-CSF barrier plays an important role in the pathophysiology of neuroinflammation and neuroinfection, via changes in the transport processes controlling the CSF biodisposition of PGE2.

Animals↗

Mechanism by which positive end-expiratory pressure increases cerebrospinal fluid pressure in dogs.

We investigated possible mechanisms by which positive end-expiratory pressure (PEEP) increased cerebrospinal fluid pressure (PCSF) in anesthetized mechanically ventilated dogs. In part I of the study, PEEP was applied in 5 cmH2O increments each lasting 1-2 min, before and after a snare separated the spinal from the cerebral subarachnoid space in each animal. Next, with the spinal cord still ligated, the dogs were ventilated without PEEP while superior vena cava pressure (PSVC) was raised in 5 cmH2O increments by means of a fluid reservoir connected with the superior vena cava. Cerebrospinal fluid pressure in the cisterna magna increased immediately and in parallel with PEEP before and after the spinal subarachnoid space was occluded and also increased when PSVC was raised independently; in all circumstances the increase in PCSF correlated closely with PSVC (r = 0.926). In part II of the study, arterial blood gases were drawn before and after PEEP was applied in the same increments and for the same duration as in part I. Cerebrospinal fluid pressure measured with a hollow skull screw again rose in parallel with PEEP, whereas arterial carbon dioxide tension rose only slightly at 60 s. In part III of the study, mean arterial pressure (Pa) was allowed to decrease with PEEP or was held constant by distal aortic obstruction and volume infusion. Cerebrospinal fluid pressure increased regardless of Pa, but the increase was greater when Pa was held constant than when it fell with PEEP. We conclude that PEEP increases PCSF primarily by increasing PSVC and decreasing cerebral venous outflow. This effect is augmented if cerebral arterial inflow is increased as well.

Animals↗

Fluid secretion in arachnoid cysts as a clue to cerebrospinal fluid absorption at the arachnoid granulation.

The morphological similarity of the lining of arachnoid cysts to subdural neurothelium and the mesothelium of arachnoid granulations suggested that the latter tissues might be the origin of arachnoid cysts. Transport Na+-K+-adenosine triphosphatase was shown by enzyme ultracytochemistry to be an indication of secretory activity in the lining of arachnoid cysts and in the endothelial lining of arachnoid granulations. This secretory activity suggests the existence of a biochemical mechanism for cerebrospinal fluid absorption at these granulations separate from the mechanisms already demonstrated.

Absorption↗