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Fluids and Barriers of the CNS

Ritambhar Burman, Noam Alperin, Sang H Lee, Brigit Ertl-Wagner
BACKGROUND: The distribution of cranio-spinal compliance (CSC) in the brain and spinal cord is a fundamental question, as it would determine the overall role of the compartments in modulating ICP in healthy and diseased states. Invasive methods for measurement of CSC using infusion-based techniques provide overall CSC estimate, but not the individual sub-compartmental contribution. Additionally, the outcome of the infusion-based method depends on the infusion site and dynamics. This article presents a method to determine compliance distribution between the cranium and spinal canal non-invasively using data obtained from patients...
November 15, 2018: Fluids and Barriers of the CNS
R Dersch, D Benkler, T Robinson, A Baumgartner, S Rauer, O Stich
BACKGROUND: Cerebrospinal fluid (CSF) analysis is a crucial method in the diagnostic process for suspected subarachnoid hemorrhage (SAH), especially when cerebral imaging is negative or inconclusive. CSF cytology (detection of erythrophages or siderophages) is used to determine whether a bloodstained CSF resembles a genuine SAH. Whether erythrophages may develop in vitro after a traumatic puncture in case of delayed CSF analysis is unclear. An in vitro development of erythrophages after traumatic puncture would diminish the diagnostic properties of CSF analysis...
November 5, 2018: Fluids and Barriers of the CNS
Stephen B Hladky, Margery A Barrand
This review considers efflux of substances from brain parenchyma quantified as values of clearances (CL, stated in µL g-1  min-1 ). Total clearance of a substance is the sum of clearance values for all available routes including perivascular pathways and the blood-brain barrier. Perivascular efflux contributes to the clearance of all water-soluble substances. Substances leaving via the perivascular routes may enter cerebrospinal fluid (CSF) or lymph. These routes are also involved in entry to the parenchyma from CSF...
October 19, 2018: Fluids and Barriers of the CNS
Mariella Errede, Domenica Mangieri, Giovanna Longo, Francesco Girolamo, Ignazio de Trizio, Antonella Vimercati, Gabriella Serio, Karl Frei, Roberto Perris, Daniela Virgintino
BACKGROUND: Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors...
October 5, 2018: Fluids and Barriers of the CNS
Eva Kjer Oernbo, Kasper Lykke, Annette Buur Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher, Nanna MacAulay
BACKGROUND: Cerebral edema can cause life-threatening increase in intracranial pressure. Besides surgical craniectomy performed in severe cases, osmotherapy may be employed to lower the intracranial pressure by osmotic extraction of cerebral fluid upon intravenous infusion of mannitol or NaCl. A so-called rebound effect can, however, hinder continuous reduction in cerebral fluid by yet unresolved mechanisms. METHODS: We determined the brain water and electrolyte content in healthy rats treated with osmotherapy...
September 25, 2018: Fluids and Barriers of the CNS
Daphne M P Naessens, Judith de Vos, Ed VanBavel, Erik N T P Bakker
BACKGROUND: Hypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Both in humans and animal models of hypertension, neuropathological features such as brain atrophy and oedema have been reported. We hypothesised that cerebrovascular damage resulting from chronic hypertension would manifest itself in a more permeable blood-brain barrier and blood-cerebrospinal fluid barrier. In addition, more leaky barriers could potentially contribute to an enhanced interstitial fluid and cerebrospinal fluid formation, which could, in turn, lead to an elevated intracranial pressure...
September 24, 2018: Fluids and Barriers of the CNS
Esmeralda K Bosma, Cornelis J F van Noorden, Reinier O Schlingemann, Ingeborg Klaassen
Breakdown of the blood-brain barrier (BBB) or inner blood-retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively...
September 20, 2018: Fluids and Barriers of the CNS
Hrvoje Brzica, Wazir Abdullahi, Bianca G Reilly, Patrick T Ronaldson
BACKGROUND: Targeting endogenous blood-brain barrier (BBB) transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) can facilitate drug delivery for treatment of neurological diseases. Advancement of Oatp targeting for optimization of CNS drug delivery requires characterization of sex-specific differences in BBB expression and/or activity of this transporter. METHODS: In this study, we investigated sex differences in Oatp1a4 functional expression at the BBB in adult and prepubertal (i...
September 13, 2018: Fluids and Barriers of the CNS
Nienke R Wevers, Dhanesh G Kasi, Taylor Gray, Karlijn J Wilschut, Benjamin Smith, Remko van Vught, Fumitaka Shimizu, Yasuteru Sano, Takashi Kanda, Graham Marsh, Sebastiaan J Trietsch, Paul Vulto, Henriëtte L Lanz, Birgit Obermeier
BACKGROUND: Receptor-mediated transcytosis is one of the major routes for drug delivery of large molecules into the brain. The aim of this study was to develop a novel model of the human blood-brain barrier (BBB) in a high-throughput microfluidic device. This model can be used to assess passage of large biopharmaceuticals, such as therapeutic antibodies, across the BBB. METHODS: The model comprises human cell lines of brain endothelial cells, astrocytes, and pericytes in a two-lane or three-lane microfluidic platform that harbors 96 or 40 chips, respectively, in a 384-well plate format...
August 31, 2018: Fluids and Barriers of the CNS
Brett A Johnson, Margaret Coutts, Hillary M Vo, Xinya Hao, Nida Fatima, Maria J Rivera, Robert J Sims, Michael J Neel, Young-Jin Kang, Edwin S Monuki
BACKGROUND: Choroid plexus epithelial cells express high levels of transthyretin, produce cerebrospinal fluid and many of its proteins, and make up the blood-cerebrospinal fluid barrier. Choroid plexus epithelial cells are vital to brain health and may be involved in neurological diseases. Transgenic mice containing fluorescent and luminescent reporters of these cells would facilitate their study in health and disease, but prior transgenic reporters lost expression over the early postnatal period...
August 16, 2018: Fluids and Barriers of the CNS
Monica D Okon, Cynthia J Roberts, Ashraf M Mahmoud, Andrew N Springer, Robert H Small, John M McGregor, Steven E Katz
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of abnormally high intracranial pressure with an unknown etiology. The objective of this study is to characterize craniospinal compliance and measure the cerebrospinal fluid (CSF) pressure waveform as CSF is passively drained during a diagnostic and therapeutic lumbar puncture (LP) in IIH. METHODS: Eighteen subjects who met the Modified Dandy Criteria, including papilledema and visual field loss, received an ultrasound guided LP where CSF pressure (CSFP) was recorded at each increment of CSF removal...
August 1, 2018: Fluids and Barriers of the CNS
Julian Rey, Malisa Sarntinoranont
BACKGROUND: In animal models, dissolved compounds in the subarachnoid space and parenchyma have been found to preferentially transport through the cortex perivascular spaces (PVS) but the transport phenomena involved are unclear. METHODS: In this study two hydraulic network models were used to predict fluid motion produced by blood vessel pulsations and estimate the contribution made to solute transport in PVS and parenchyma. The effect of varying pulse amplitude and timing, PVS dimensions, and tissue hydraulic conductivity on fluid motion was investigated...
July 16, 2018: Fluids and Barriers of the CNS
Servio H Ramirez, Allison M Andrews, Debayon Paul, Joel S Pachter
Extracellular vesicles (EVs) are heterogeneous, nano-sized vesicles that are shed into the blood and other body fluids, which disperse a variety of bioactive molecules (e.g., protein, mRNA, miRNA, DNA and lipids) to cellular targets over long and short distances. EVs are thought to be produced by nearly every cell type, however this review will focus specifically on EVs that originate from cells at the interface of CNS barriers. Highlighted topics include, EV biogenesis, the production of EVs in response to neuroinflammation, role in intercellular communication and their utility as a therapeutic platform...
July 1, 2018: Fluids and Barriers of the CNS
Mohammad M Faghih, M Keith Sharp
BACKGROUND: Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow-Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels...
June 15, 2018: Fluids and Barriers of the CNS
Bujung Hong, Manolis Polemikos, Hans E Heissler, Christian Hartmann, Makoto Nakamura, Joachim K Krauss
BACKGROUND: Cerebrospinal fluid (CSF) circulation disturbances may occur during the course of disease in patients with glioblastoma. Ventriculoperitoneal shunting has generally been recommended to improve symptoms in glioblastoma patients. Shunt implantation for patients with glioblastoma, however, presents as a complex situation and produces different problems to shunting in other contexts. Information on complications of shunting glioma patients has rarely been the subject of investigation...
June 4, 2018: Fluids and Barriers of the CNS
Edward G Stopa, Keith Q Tanis, Miles C Miller, Elena V Nikonova, Alexei A Podtelezhnikov, Eva M Finney, David J Stone, Luiz M Camargo, Lisan Parker, Ajay Verma, Andrew Baird, John E Donahue, Tara Torabi, Brian P Eliceiri, Gerald D Silverberg, Conrad E Johanson
BACKGROUND: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states. METHODS: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP. RNA from post-mortem samples of the entire lateral ventricular choroid plexus was extracted from 6 healthy controls (Ctrl), 7 patients with advanced (Braak and Braak stage III-VI) Alzheimer's disease (AD), 4 with frontotemporal dementia (FTD) and 3 with Huntington's disease (HuD)...
May 31, 2018: Fluids and Barriers of the CNS
Judie B Alimonti, Maria Ribecco-Lutkiewicz, Caroline Sodja, Anna Jezierski, Danica B Stanimirovic, Qing Liu, Arsalan S Haqqani, Wayne Conlan, Mahmud Bani-Yaghoub
Zika virus (ZIKV) is a flavivirus that is highly neurotropic causing congenital abnormalities and neurological damage to the central nervous systems (CNS). In this study, we used a human induced pluripotent stem cell (iPSC)-derived blood brain barrier (BBB) model to demonstrate that ZIKV can infect brain endothelial cells (i-BECs) without compromising the BBB barrier integrity or permeability. Although no disruption to the BBB was observed post-infection, ZIKV particles were released on the abluminal side of the BBB model and infected underlying iPSC-derived neural progenitor cells (i-NPs)...
May 15, 2018: Fluids and Barriers of the CNS
Domenico L Di Curzio, Xiaoyan Mao, Aidan Baker, Marc R Del Bigio
Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca2+ channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness...
May 3, 2018: Fluids and Barriers of the CNS
Shinuo Liu, Magdalena A Lam, Alisha Sial, Sarah J Hemley, Lynne E Bilston, Marcus A Stoodley
BACKGROUND: Cerebrospinal fluid (CSF) is thought to flow into the brain via perivascular spaces around arteries, where it mixes with interstitial fluid. The precise details concerning fluid outflow remain controversial. Although fluid dynamics have been studied in the brain, little is known about spinal cord fluid inflow and outflow. Understanding the normal fluid physiology of the spinal cord may give insight into the pathogenesis of spinal cord oedema and CSF disorders such as syringomyelia...
April 29, 2018: Fluids and Barriers of the CNS
Midrelle E Noumbissi, Bianca Galasso, Monique F Stins
The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter...
April 23, 2018: Fluids and Barriers of the CNS
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