Review of "The Blood-Cerebrospinal Fluid Barrier" by Wei Zheng and Adam Chodobski (editors)

This multi-author volume on the blood-cerebrospinal fluid barrier summarizes past and current research in the areas of choroid plexus and cerebrospinal fluid in health and disease

Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance

<p>Abstract</p> <p>Background</p> <p>A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (<it>C</it>_out) or its reciprocal the outflow resistance (<it>R</it>_out), with or without using the baseline resting pressure, <it>P</it>_r. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating <it>C</it>_out using two different analyses, with or without <it>P</it>_r, the limitations could be explored. The aim of this study was to compare the <it>C</it>_out estimates, and investigate what effect <it>P</it>_rhad on the results.</p> <p>Methods</p> <p>Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3 ± 10.8 years (mean ± SD)). The analysis was performed without (<it>C</it>_{excl Pr}) and with (<it>C</it>_{incl Pr}) P_r. The estimates were compared using Bland-Altman plots and paired sample <it>t</it>-tests (<it>p </it>< 0.05 considered significant).</p> <p>Results</p> <p>Mean <it>C</it>_out for the 63 patients was: <it>C</it>_{excl Pr}= 7.0 ± 4.0 (mean ± SD) μl/(s kPa) and <it>C</it>_{incl Pr} = 9.1 ± 4.3 μl/(s kPa) and <it>R</it>_out was 19.0 ± 9.2 and 17.7 ± 11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r = 0.79, n = 63, <it>p </it>< 0.01). The difference, Δ<it>C</it>_out= -2.1 ± 2.7 μl/(s kPa) between methods was significant (<it>p </it>< 0.01) and Δ<it>R</it>_outwas 1.2 ± 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between Δ<it>C</it>_outand <it>C</it>_out.</p> <p>Conclusions</p> <p>The difference between <it>C</it>_outestimates, obtained from analyses with or without <it>P</it>_r, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent <it>C</it>_outas possible causes for the deviation from the CSF absorption model seen in some patients.</p

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

Fluids and barriers of the CNS: a historical viewpoint

Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF) into all barriers of the central nervous system (CNS), this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century

Multiple Traits for People Identification

Present biometric systems mostly rely on a single physical or behavioral feature for either identification or verification. However, day to day use of single biometries in massive or uncontrolled scenarios still has several shortcomings. These can be due to complex or unstable hardware settings, to changing environmental conditions or even to immature software procedures: some classification problems are intrinsically hard to solve. Possible spoofing of single biometric features is an additional issue. Last but not least, some features may occasionally lack the requisite of universality. As a consequence, biometric systems based on a single feature often have poor reliability, especially in applications where high security is needed. Multimodal systems, i.e., systems that concurrently exploit multiple features, are a possible way to achieve improved effectiveness and reliability. There are several issues that must be addressed when designing such a system, including the choice of the set of biometric features, the normalization method, the integration schema and the fusion process, and the use of a measure of reliability for each subsystem on a single response basis. This chapter describes the state of the art regarding such issues and sketches some suggestions for future work

Water Solubilization Using Nonionic Surfactants from Renewable Sources in Microemulsion Systems

In this study the effect of temperature, NaCl and oils (hydrocarbons: C8–C16) on the formation and solubilization capacity of the systems of oil/monoacylglycerols (MAG):ethoxylated fatty alcohols (CEO20)/propylene glycol (PG)/water was investigated. The effects of the surfactant mixture on the phase behavior and the concentration of water or oil in the systems were studied at three temperatures (50, 55, 60 °C) and with varied NaCl solutions (0.5; 2; 11%). Electrical conductivity measurement, FTIR spectroscopy and the DSC method were applied to determine the structure and type of the microemulsions formed. The dimension of the microemulsion droplets was characterized by dynamic light scattering. It has been stated that the concentration of CEO20 has a strong influence on the shape and extent of the microemulsion areas. Addition of a nonionic surfactant to the mixture with MAG promotes an increase in the area of microemulsion formation in the phase diagrams, and these areas of isotropic region did not change considerably depending on the temperature, NaCl solution and oil type. It was found that, depending on the concentration of the surfactant mixture, it was possible to obtain U-type microemulsions with dispersed particles size distribution ranging from 25 to 50 nm and consisting of about 30–32% of the water phase in the systems. The conditions under which the microemulsion region was found (electrolyte and temperature—insensitive, comparatively low oil and surfactant concentration) could be highly useful in detergency

Expression and functional activity of nucleoside transporters in human choroid plexus

Abstract Background Human equilibrative nucleoside transporters (hENTs) 1-3 and human concentrative nucleoside transporters (hCNTs) 1-3 in the human choroid plexus (hCP) play a role in the homeostasis of adenosine and other naturally occurring nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane transport of nucleoside reverse transcriptase inhibitors that could be used to treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'-dideoxyinosine. This study aimed to explore the expression levels and functional activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus. Methods Freshly-isolated pieces of lateral ventricle hCP, removed for various clinical reasons during neurosurgery, were obtained under Local Ethics Committee approval. Quantification of mRNAs that encoded hENTs and hCNTs was performed by the hydrolysis probes-based reverse transcription real time-polymerase chain reaction (RT-qPCR); for each gene of interest and for 18 S ribosomal RNA, which was an endogenous control, the efficiency of PCR reaction (E) and the quantification cycle (Cq) were calculated. The uptake of [3H]inosine by the choroid plexus pieces was investigated to explore the functional activity of hENTs and hCNTs in the hCP. Results RT-qPCR revealed that the mRNA encoding the intracellularly located transporter hENT3 was the most abundant, with E-Cq value being only about 40 fold less that the E-Cq value for 18 S ribosomal RNA; mRNAs encoding hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable. Uptake of [3H]inosine by the CP samples was linear and consisted of an Na+-dependent component, which was probably mediated by hCNT3, and Na+-independent component, mediated by hENTs. The latter component was not sensitive to inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), when used at a concentration of 0.5 μM, a finding that excluded the involvement of hENT1, but it was very substantially inhibited by 10 μM NBMPR, a finding that suggested the involvement of hENT2 in uptake. Conclusion Transcripts for hENT1-3 and hCNT3 were detected in human CP; mRNA for hENT3, an intracellularly located nucleoside transporter, was the most abundant. Human CP took up radiolabelled inosine by both concentrative and equilibrative processes. Concentrative uptake was probably mediated by hCNT3; the equilibrative uptake was mediated only by hENT2. The hENT1 transport activity was absent, which could suggest either that this protein was absent in the CP cells or that it was confined to the basolateral side of the CP epithelium.</p