Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection

Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection

Embryonic cerebrospinal fluid influence in the subependymal neurogenic niche in adult mouse hippocampus

Producción CientíficaThe adult mouse hippocampal neurogenic niche is a complex structure which is not completely understood. It has mainly been related to the Subgranular layer of the dentate gyrus; however, as a result of differential neural stem cell populations reported in the subventricular zone of the lateral ventricle and associated with the hippocampus, the possibility remains of a multifocal niche reproducing developmental stages. Here, using a set of molecular markers for neural precursors, we describe in the adult mouse brain hippocampus the existence of a disperse population of neural precursors in the Subependymal Zone, the Dentate Migratory Stream and the hilus; these display dynamic behaviour compatible with neurogenesis. This supports the idea that the adult hippocampal niche cannot be restricted to the dentate gyrus subgranular layer. In other neurogenic niches such as the Subventricular Zone, a functional periventricular dependence has been shown due to the ability to respond to embryonic cerebro-spinal fluid. In this study, we demonstrate that neural precursors from the three areas studied (Sub-ependymal Zone, Dentate Migratory Stream and hilus) are able to modify their behaviour by increasing neurogenesis in a locally differential manner. Our results are compatible with the persistence in the adult mouse hippocampus of a neurogenic niche with the same spatial structure as that seen during development and early postnatal stages.Ministerio de Educación y Ciencia (BFU207/6516)Junta de Castilla y León (Consejería de Educación, GR195

Ion beam sputter-etched ventricular catheter for hydrocephalus shunt

A cerebrospinal fluid shunt in the form of a ventricular catheter for controlling the condition of hydrocephalus by relieving the excessive cerebrospinal fluid pressure is described. A method for fabrication of the catheter and shunting the cerebral fluid from the cerebral ventricles to other areas of the body is also considered. Shunt flow failure occurs if the ventricle collapse due to improper valve function causing overdrainage. The ventricular catheter comprises a multiplicity of inlet microtubules. Each microtubule has both a large openings at its inlet end and a multiplicity of microscopic openings along its lateral surfaces

Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett Syndrome

Objective: Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs) play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. Methods: The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life) and from Rett syndrome patients (2 to 19 years of life), by immunoblot analysis. Results: Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. Conclusions: Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective

Drug transport in brain via the cerebrospinal fluid

The human brain has no lymphatic system, but produces over a half-liter each day of cerebrospinal fluid. The cerebrospinal fluid is secreted at the choroid plexus and occupies the cavities of the four ventricles, as well as the cranial and spinal sub-arachnoid space. The cerebrospinal fluid moves over the surfaces of the brain and spinal cord and is rapidly absorbed into the general circulation. The choroid plexus forms the blood-cerebrospinal fluid barrier, and this barrier is functionally distinct from the brain microvascular endothelium, which forms the blood-brain barrier. Virtually all non-cellular substances in blood distribute into cerebrospinal fluid, and drug entry into cerebrospinal fluid is not an index of drug transport across the blood-brain barrier. Drug injected into the cerebrospinal fluid rapidly moves into the blood via bulk flow, but penetrates into brain tissue poorly owing to the limitations of diffusion. Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium

Cerebrospinal Fluid

Cerebrospinal fluid is an essential, clear, and colorless liquid essential for maintaining homeostasis of the brain and neuronal functioning. Its secretion in adults ranges from 400 to 600 ml per day and it is renewed about four or five times daily. Cerebrospinal fluid is mainly reabsorbed from arachnoid granulations. Any disruption in this well-regulated system, such as overproduction, decreased absorption, or obstruction, could lead to hydrocephalus. This book contains essential knowledge about cerebrospinal fluid anatomy and physiology, pathologies related to cerebrospinal fluid, and treatment strategies for cerebrospinal fluid disorders

Outcomes of Tuberculous Meningitis Patients with Hydrocephalus with or without Cerebrospinal Fluid Diversion

Background: Hydrocephalus is a common complication in tuberculous meningitis patients and is a poor predictor with high mortality and morbidity rates. Therefore, early diagnosis, detection, and treatment of hydrocephalus are important. Cerebrospinal fluid diversion is the process used to drain accumulated fluid in the brain and spinal cord. This study aimed to explore the outcome of tuberculous meningitis patients with hydrocephalus who underwent cerebrospinal fluid diversion and who did not.Methods: This was a retrospective cross-sectional descriptive study, including tuberculosis meningitis patients with hydrocephalus, admitted at the Department of Neurology Dr. Hasan Sadikin Bandung General Hospital during the period 2018. Functional outcomes were grouped based on the Glasgow Outcome Scale.Results: Of the 55 patients, only 14 (25.5%) underwent cerebrospinal fluid diversion. The outcome of patients with cerebrospinal fluid diversion was 8 of 14 good, 1 of 14 poor, and 5 of 14 died. The outcome of patients without cerebrospinal fluid diversion was 13 of 41 good, 2 of 41 poor, and 26 of 41 died. Most tuberculous meningitis patients with hydrocephalus, with or without the cerebrospinal fluid diversion procedure were at an advanced stage with a high mortality rate. Conclusion: The proportion of good functional outcomes in patients with cerebrospinal fluid diversion is higher than in patients without the cerebrospinal fluid diversion.

Spectrophotometry for cerebrospinal fluid pigment analysis

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined

Physiological Characteristics of Some Monoamine Metabolites in Cat Cerebrospinal Fluid

The concentrations of main metabolites of serotonin and dopamine, 5-hydroxyindoleacetic acid and homovanillic acid, respectively, were measured in cisternal cerebrospinal fluid of cats by high performance liquid chromatography with an electrochemical detector. Higher concentrations of homovanillic acid and a wide interindividual oscillation for both parameters have been found. However, samples collected at four different time intervals showed stabile intraindividual concentrations of the metabolites. The existence of a concentration gradient of both parameters inside the cat cerebrospinal fluid system was confirmed in experiments with a provoked artificial flow of cerebrospinal fluid inside physiological limits. These experiments also suggested that the hydrodynamics of cerebrospinal fluid is the factor responsible for the concentration gradient existence. It appears that the absence of cerebrospinal fluid circulation is the main hydrodynamic reason for the maintenance of 5-hydroxyindoleacetic acid and homovanillic add gradients between various parts of the cerebrospinal fluid system

The Iodide Space in Rabbit Brain

In the present investigation labeled iodide was used to investigate the interrelationship between brain, blood and cerebrospinal fluid, to examine active transport across the blood-brain- and the blood-cerebrospinal fluid barriers, and to estimate the extracellular space of the brain. The iodide space in the brain and the iodide concentration in cerebrospinal fluid after intravenous administration of radioactive iodide are determined by the following mechanisms. Iodide passes into the cerebrospinal fluid but active transport in the choroid plexus moves most of the iodide back again into the plasma, keeping the concentration at a very law value. An extracellular fluid is formed at the blood-brain barrier possibly in a similar way. The iodide concentration of this fluid is unknown but is probably higher than that in the cerebrospinal fluid. Diffusion of iodide across the brain-cerebrospinal fluid barrier transports this ion from the brain into the cerebrospinal fluid which is constantly renewed "sink action". The iodide space was found to be 2.4% four to five hours after the intravenous administration of 131I, the iodide content of the cerebrospinal fluid was 1.2% of that of the TCA serum filtrate. The iodide space increased to 10.6% in preparations in which in addition to 131I unlabeled iodide (to a serum concentration of 25 to 50 mM) was administered to saturate the active transport processes in the choroid plexuses and blood-brain barrier. The iodide activity of the cerebrospinal fluid in these experiments increased to 29.3% of that in the TCA serum filtrate. In experiments in which the inhibitor of iodide transport, perchlorate (8 mM), was injected intravenously with the 131I-, the iodide space was 8.2% and the iodide concentration in the cerebrospinal fluid 26.4%. These experiments demonstrate the effect of saturation and inhibition of active transport on the iodide space. They show furthermore that the depression of the active transport did not raise the iodide concentration in the cerebrospinal fluid to the plasma concentration. The relatively low (1/3 of that in the serum TCA filtrate) iodide concentration in the cerebrospinal fluid under these circumstances was ascribed to a differential permeability of the blood-cerebrospinal fluid barrier for iodide and chloride. The sink action can be eliminated by perfusion of the ventricles with an artificial cerebrospinal fluid containing iodide. Ventriculocisternal perfusion with 131I- alone resulted in an iodide space of 7.2% after 4.5 hours. An iodide space of 10.2% was determined by a combined intravenous administration and ventricular perfusion with an artificial cerebrospinal fluid containing the same concentration of 131I as present in the plasma. When in similar experiments perchlorate was administered intravenously, the iodide space rose to 16.8%. The iodide space determined by simultaneous intravenous injection and ventricular perfusion with both labeled and unlabeled iodide, in a concentration sufficient to saturate the active transport, was 20.8%. In the latter instances the sink action is eliminated and also active transport is inhibited or saturated. It was postulated that under these conditions the iodide concentration in plasma and brain extracellular fluid are approximately the same. The use of the iodide space as a measure of the brain extracellular space was discussed.</p