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Fluids and Barriers of the CNS

Miles Hudson, Caden Nowak, Richard J Garling, Carolyn Harris
Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of hydrocephalus that occurs more often in the elderly population. It is usually characterized by gait disturbance, dementia and urinary incontinence. Epidemiological studies indicate that 15.7-17.8% of iNPH patients present with type-2 diabetes mellitus (DM). A review of the primary literature shows that these occurrence rates are higher than age- and cohort-matched non-iNPH controls. This suggests that this already vulnerable patient group has an increased risk for presenting with DM compared to their non-iNPH counterparts...
February 12, 2019: Fluids and Barriers of the CNS
Richard F Keep, Hazel C Jones, Lester R Drewes
This editorial focuses on the progress made in brain barrier and brain fluid research in 2018. It highlights some recent advances in knowledge and techniques, as well as prevalent themes and controversies. Areas covered include: modeling, the brain endothelium, the neurovascular unit, the blood-CSF barrier and CSF, drug delivery, fluid movement within the brain, the impact of disease states, and heterogeneity.
February 5, 2019: Fluids and Barriers of the CNS
Chris Greene, Nicole Hanley, Matthew Campbell
Tight junction proteins of the blood-brain barrier are vital for maintaining integrity of endothelial cells lining brain blood vessels. The presence of these protein complexes in the space between endothelial cells creates a dynamic, highly regulated and restrictive microenvironment that is vital for neural homeostasis. By limiting paracellular diffusion of material between blood and brain, tight junction proteins provide a protective barrier preventing the passage of unwanted and potentially damaging material...
January 29, 2019: Fluids and Barriers of the CNS
Robert B Hamilton, Fabien Scalzo, Kevin Baldwin, Amber Dorn, Paul Vespa, Xiao Hu, Marvin Bergsneider
BACKGROUND: This study investigated cerebrospinal fluid (CSF) hydrodynamics using cine phase-contrast MRI in the cerebral aqueduct and the prepontine cistern between three distinct groups: pre-shunt normal pressure hydrocephalus (NPH) patients, post-shunt NPH patients, and controls. We hypothesized that the hyperdynamic flow of CSF through the cerebral aqueduct seen in NPH patients was due to a reduction in cisternal CSF volume buffering. Both hydrodynamic (velocity, flow, stroke volume) and peak flow latency (PFL) parameters were investigated...
January 22, 2019: Fluids and Barriers of the CNS
Therese S Salameh, William G Mortell, Aric F Logsdon, D Allan Butterfield, William A Banks
BACKGROUND: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood-retinal barrier (BRB) and blood-brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress...
January 8, 2019: Fluids and Barriers of the CNS
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December 24, 2018: Fluids and Barriers of the CNS
Braden J Lawrence, Aintzane Urbizu, Philip A Allen, Francis Loth, R Shane Tubbs, Alexander C Bunck, Jan-Robert Kröger, Brandon G Rocque, Casey Madura, Jason A Chen, Mark G Luciano, Richard G Ellenbogen, John N Oshinski, Bermans J Iskandar, Bryn A Martin
BACKGROUND: Type 1 Chiari malformation (CM-I) has been historically defined by cerebellar tonsillar position (TP) greater than 3-5 mm below the foramen magnum (FM). Often, the radiographic findings are highly variable, which may influence the clinical course and patient outcome. In this study, we evaluate the inter-operator reliability (reproducibility) of MRI-based measurement of TP in CM-I patients and healthy controls. METHODS: Thirty-three T2-weighted MRI sets were obtained for 23 CM-I patients (11 symptomatic and 12 asymptomatic) and 10 healthy controls...
December 17, 2018: Fluids and Barriers of the CNS
Shawn Kant, Edward G Stopa, Conrad E Johanson, Andrew Baird, Gerald D Silverberg
BACKGROUND: The roles of the choroid plexus (CP) and cerebrospinal fluid (CSF) production have drawn increasing attention in Alzheimer's disease (AD) research. Specifically, studies document markedly decreased CSF production and turnover in moderate-to-severe AD. Moreover, reduced CP function and CSF turnover lead to impaired clearance of toxic metabolites, likely promote neuroinflammation, and may facilitate neuronal death during AD progression. We analyzed CP gene expression in AD compared with control subjects, specifically considering those genes involved with CSF production and CP structural integrity...
December 12, 2018: Fluids and Barriers of the CNS
Jackson G DeStefano, John J Jamieson, Raleigh M Linville, Peter C Searson
The blood-brain barrier (BBB) plays a key role in regulating transport into and out of the brain. With increasing interest in the role of the BBB in health and disease, there have been significant advances in the development of in vitro models. The value of these models to the research community is critically dependent on recapitulating characteristics of the BBB in humans or animal models. However, benchmarking in vitro models is surprisingly difficult since much of our knowledge of the structure and function of the BBB comes from in vitro studies...
December 4, 2018: 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
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