Articles

In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy

Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investig...

Authors: Mohammadreza Khani, Lucas R. Sass, M. Keith Sharp, Aaron R. McCabe, Laura M. Zitella Verbick, Shivanand P. Lad and Bryn A. Martin

In vitro modeling of the neurovascular unit: advances in the field

The blood–brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the oth...

Authors: Aditya Bhalerao, Farzane Sivandzade, Sabrina Rahman Archie, Ekram Ahmed Chowdhury, Behnam Noorani and Luca Cucullo

Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models

The blood–brain barrier (BBB) maintains homeostasis of the brain environment by tightly regulating the entry of substances from systemic circulation. A breach in the BBB results in increased permeability to po...

Authors: Kyeong-A Kim, Donghyun Kim, Jeong-Hyeon Kim, Young-Jun Shin, Eun-Sun Kim, Muhammad Akram, Eun-Hye Kim, Arshad Majid, Seung-Hoon Baek and Ok-Nam Bae

This was the year that was: brain barriers and brain fluid research in 2019

This editorial highlights advances in brain barrier and brain fluid research published in 2019, as well as addressing current controversies and pressing needs. Topics include recent advances related to: the ce...

Authors: Richard F. Keep, Hazel C. Jones and Lester R. Drewes

The pivotal role of micro-environmental cells in a human blood–brain barrier in vitro model of cerebral ischemia: functional and transcriptomic analysis

The blood–brain barrier (BBB) is altered in several diseases of the central nervous system. For example, the breakdown of the BBB during cerebral ischemia in stroke or traumatic brain injury is a hallmark of t...

Authors: Anna Gerhartl, Nadja Pracser, Alexandra Vladetic, Sabrina Hendrikx, Heinz-Peter Friedl and Winfried Neuhaus

Secondary deterioration in patients with normal pressure hydrocephalus after ventriculoperitoneal shunt placement: a proposed algorithm of treatment

After ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) with adjustable gravitational valves, a certain proportion of patients develop secondary clinical worsening after in...

Authors: Pawel Gutowski, Sergej Rot, Michael Fritsch, Ullrich Meier, Leonie Gölz and Johannes Lemcke

Abnormalities in spinal cord ultrastructure in a rat model of post-traumatic syringomyelia

Syringomyelia is a serious complication of spinal cord trauma, occurring in approximately 28% of spinal cord injuries. Treatment options are limited and often produce unsatisfactory results. Post-traumatic syr...

Authors: Joel Berliner, Sarah Hemley, Elmira Najafi, Lynne Bilston, Marcus Stoodley and Magdalena Lam

Effects of aging on hydrocephalus after intraventricular hemorrhage

Hydrocephalus is a common and major complication that affects outcome after intraventricular hemorrhage (IVH). While aging impacts the occurrence of hydrocephalus in patients with IVH this and the underlying m...

Authors: Yingfeng Wan, Feng Gao, Fenghui Ye, Weiming Yang, Ya Hua, Richard F. Keep and Guohua Xi

Chemokine CXCL13 in serum, CSF and blood–CSF barrier function: evidence of compartment restriction

Elevation of the chemokine CXCL13 in CSF frequently occurs during active and acute CNS inflammatory processes and presumably is associated with B cell-related immune activation. Elevation levels, however, vary...

Authors: Georg Pilz, Irma Sakic, Peter Wipfler, Jörg Kraus, Elisabeth Haschke-Becher, Wolfgang Hitzl, Eugen Trinka and Andrea Harrer

Corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in...

Authors: Jani Sirkka, Laura Säisänen, Petro Julkunen, Mervi Könönen, Elisa Kallioniemi, Ville Leinonen and Nils Danner

Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance

Cerebrospinal fluid (CSF) is mainly produced by the choroid plexus (CP) located in brain ventricles. Although derived from blood plasma, it is nearly protein-free (~ 250-fold less) and contains about 2–20-fold...

Authors: Elena Dolgodilina, Simone M. Camargo, Eva Roth, Brigitte Herzog, Virginia Nunes, Manuel Palacín and Francois Verrey

Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

The endothelial cell–cell junctions of the blood–brain barrier (BBB) play a pivotal role in the barrier’s function. Altered cell–cell junctions can lead to barrier dysfunction and have been implicated in sever...

Authors: Kelsey M. Gray, Jae W. Jung, Collin T. Inglut, Huang-Chiao Huang and Kimberly M. Stroka

Aquaporin 1 and the Na⁺/K⁺/2Cl⁻ cotransporter 1 are present in the leptomeningeal vasculature of the adult rodent central nervous system

The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), ...

Authors: Qianliang Li, Nadia N. Aalling, Benjamin Förstera, Ali Ertürk, Maiken Nedergaard, Kjeld Møllgård and Anna L. R. Xavier

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obes...

Authors: Zerin Alimajstorovic, Ester Pascual-Baixauli, Cheryl A. Hawkes, Basil Sharrack, A. Jane Loughlin, Ignacio A. Romero and Jane E. Preston

Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage

Excitotoxicity is a central pathological pathway in many neurological diseases with blood–brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, b...

Authors: Lilla Barna, Fruzsina R. Walter, András Harazin, Alexandra Bocsik, András Kincses, Vilmos Tubak, Katalin Jósvay, Ágnes Zvara, Patricia Campos-Bedolla and Mária A. Deli

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood–cerebrospinal fluid barrier (B-CSF-B) permeability. For years QAlb was considered only as a...

Authors: Massimiliano Castellazzi, Andrea Morotti, Carmine Tamborino, Francesca Alessi, Silvy Pilotto, Eleonora Baldi, Luisa M. Caniatti, Alessandro Trentini, Ilaria Casetta, Enrico Granieri, Maura Pugliatti, Enrico Fainardi and Tiziana Bellini

Hypercholesterolemia negatively influences morphology and molecular markers of epithelial cells within the choroid plexus in rabbits

Choroid plexus (CP) is an important tissue not only to produce cerebrospinal fluid (CSF) but also to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (B...

Authors: Fumiko Obata and Keishi Narita

CNS fluid and solute movement: physiology, modelling and imaging

Authors: Hazel C. Jones, Richard F. Keep and Lester R. Drewes

Human CD4⁺ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell e...

Authors: Hideaki Nishihara, Sasha Soldati, Adrien Mossu, Maria Rosito, Henriette Rudolph, William A. Muller, Daniela Latorre, Federica Sallusto, Mireia Sospedra, Roland Martin, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Fabien Gosselet and Britta Engelhardt

Longitudinal analysis of cerebral aqueduct flow measures: multiple sclerosis flow changes driven by brain atrophy

Several small cross-sectional studies have investigated cerebrospinal fluid (CSF) flow dynamics in multiple sclerosis (MS) patients and have reported mixed results. Currently, there are no longitudinal studies...

Authors: Dejan Jakimovski, Robert Zivadinov, Bianca Weinstock-Guttman, Niels Bergsland, Michael G. Dwyer and Marcella Maria Lagana

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients

Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due t...

Authors: Lucas R. Sass, Mohammadreza Khani, Jacob Romm, Marianne Schmid Daners, Kyle McCain, Tavara Freeman, Gregory T. Carter, Douglas L. Weeks, Brian Petersen, Jason Aldred, Dena Wingett and Bryn A. Martin

Extracranial versus intracranial hydro-hemodynamics during aging: a PC-MRI pilot cross-sectional study

Both aging and changes in blood flow velocity between the extracranial (intraspinal) and intracranial regions of cerebral vessels have an impact on brain hydro-hemodynamics. Arterial and venous cerebral blood ...

Authors: Armelle Lokossou, Serge Metanbou, Catherine Gondry-Jouet and Olivier Balédent

Genetic disruption of slc4a10 alters the capacity for cellular metabolism and vectorial ion transport in the choroid plexus epithelium

Genetic disruption of slc4a10, which encodes the sodium-dependent chloride/bicarbonate exchanger Ncbe, leads to a major decrease in Na⁺-dependent HCO₃⁻ import into choroid plexus epithelial cells in mice and to a...

Authors: Inga Baasch Christensen, Qi Wu, Anders Solitander Bohlbro, Marianne Gerberg Skals, Helle Hasager Damkier, Christian Andreas Hübner, Robert Andrew Fenton and Jeppe Praetorius

Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly? A prospective study of patients with communicating hydrocephalus

Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of detectable cerebrospinal fluid (CSF) outflow obstructions and often with increased CSF...

Authors: P. Holmlund, S. Qvarlander, J. Malm and A. Eklund

The legacy of Malcolm Beverley Segal (1937–2019) on the science and fields concerned with choroid plexus and cerebrospinal fluid physiology

This article highlights the scientific achievements, professional career, and personal interactions of Malcolm B. Segal who passed away in July this year. Born in 1937 in Goodmayes, Essex, UK, Segal rose to th...

Authors: Adam Chodobski, Jean-François Ghersi-Egea, Jane Preston-Kennedy, Zoran Redzic, Nathalie Strazielle, Joanna Szmydynger-Chodobska and Robert G. Thorne

Pathological mitochondria in neurons and perivascular astrocytic endfeet of idiopathic normal pressure hydrocephalus patients

A growing body of evidence suggests that the accumulation of amyloid-β and tau (HPτ) in the brain of patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) is associated with delaye...

Authors: Md Mahdi Hasan-Olive, Rune Enger, Hans-Arne Hansson, Erlend A. Nagelhus and Per Kristian Eide

Region-specific blood–brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer’s disease

Research into amisulpride use in Alzheimer’s disease (AD) implicates blood–brain barrier (BBB) dysfunction in antipsychotic sensitivity. Research into BBB transporters has been mainly directed towards the ABC ...

Authors: Gayathri Nair Sekhar, Alice L. Fleckney, Sevda Tomova Boyanova, Huzefa Rupawala, Rachel Lo, Hao Wang, Doaa B. Farag, Khondaker Miraz Rahman, Martin Broadstock, Suzanne Reeves and Sarah Ann Thomas

Repeated lumbar punctures within 3 days may affect CSF biomarker levels

Lumbar puncture (LP) is a common way of collecting cerebrospinal fluid (CSF) both in the clinic and in research. In this extension of a study on the relationship between sleep deprivation and CSF biomarkers fo...

Authors: Martin Olsson, Johan Ärlig, Jan Hedner, Kaj Blennow and Henrik Zetterberg

Abstracts from Hydrocephalus 2019: The Eleventh Meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders

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Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension

Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of...

Authors: Sajedeh Eftekhari, Connar Stanley James Westgate, Maria Schmidt Uldall and Rigmor Hoejland Jensen

Effect of blood contamination of cerebrospinal fluid on amino acids, biogenic amines, pterins and vitamins

Cerebrospinal fluid (CSF) metabolomic investigations are a powerful tool for studying neurometabolic diseases. We aimed to assess the effect of CSF contamination with blood on the concentrations of selected bi...

Authors: Marta Batllori, Mercedes Casado, Cristina Sierra, Maria del Carmen Salgado, Laura Marti-Sanchez, Joan Maynou, Guerau Fernandez, Angels Garcia-Cazorla, Aida Ormazabal, Marta Molero-Luis and Rafael Artuch

B waves: a systematic review of terminology, characteristics, and analysis methods

Although B waves were introduced as a concept in the analysis of intracranial pressure (ICP) recordings nearly 60 years ago, there is still a lack consensus on precise definitions, terminology, amplitude, freq...

Authors: Isabel Martinez-Tejada, Alexander Arum, Jens E. Wilhjelm, Marianne Juhler and Morten Andresen

Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields

Influx and clearance of substances in the brain parenchyma occur by a combination of diffusion and convection, but the relative importance of these mechanisms is unclear. Accurate modeling of tracer distributi...

Authors: Matteo Croci, Vegard Vinje and Marie E. Rognes

Claudin-12 is not required for blood–brain barrier tight junction function

The blood–brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junct...

Authors: Mariana Castro Dias, Caroline Coisne, Pascale Baden, Gaby Enzmann, Lillian Garrett, Lore Becker, Sabine M. Hölter, Martin Hrabě de Angelis, Urban Deutsch and Britta Engelhardt

Abstracts from the 22nd International Symposium on Signal Transduction at the Blood–Brain Barriers

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Correction to: An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons

Following publication of the original article [1], the author has reported that in Figure 1 (b and c) the y-axis TEER (© x cm²) should be replaced with TEER (Ω x cm²).

Authors: Scott G. Canfield, Matthew J. Stebbins, Madeline G. Faubion, Benjamin D. Gastfriend, Sean P. Palecek and Eric V. Shusta

Tau-protein concentrations are not elevated in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), caused by infection with John Cunningham polyoma virus (JCPyV) in immune-compromised patients, is a serious demyelinating disease of the central nervous system...

Authors: Nora Möhn, Yi Luo, Thomas Skripuletz, Philipp Schwenkenbecher, Inga Zerr, Peter Lange and Martin Stangel

Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood–brain barrier model

Human induced pluripotent stem cells (hiPSC) hold great promise for use in cell therapy applications and for improved in vitro models of human disease. So far, most hiPSC differentiation protocols to astroglia...

Authors: Louise Delsing, Therése Kallur, Henrik Zetterberg, Ryan Hicks and Jane Synnergren

Streptococcus agalactiae disrupts P-glycoprotein function in brain endothelial cells

Bacterial meningitis is a serious life threatening infection of the CNS. To cause meningitis, blood–borne bacteria need to interact with and penetrate brain endothelial cells (BECs) that comprise the blood–bra...

Authors: Brandon J. Kim, Maura A. McDonagh, Liwen Deng, Benjamin D. Gastfriend, Alexandra Schubert-Unkmeir, Kelly S. Doran and Eric V. Shusta

An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons

Brain microvascular endothelial cells (BMECs) astrocytes, neurons, and pericytes form the neurovascular unit (NVU). Interactions with NVU cells endow BMECs with extremely tight barriers via the expression of t...

Authors: Scott G. Canfield, Matthew J. Stebbins, Madeline G. Faubion, Benjamin D. Gastfriend, Sean P. Palecek and Eric V. Shusta

The Kuopio idiopathic normal pressure hydrocephalus protocol: initial outcome of 175 patients

The Kuopio University Hospital (KUH) idiopathic normal pressure hydrocephalus (iNPH) cerebrospinal fluid (CSF) shunting protocol is described together with the initial outcomes of 175 patients with probable iN...

Authors: A. Junkkari, A. J. Luikku, N. Danner, H. K. Jyrkkänen, T. Rauramaa, V. E. Korhonen, A. M. Koivisto, O. Nerg, M. Kojoukhova, T. J. Huttunen, J. E. Jääskeläinen and V. Leinonen

The role of mutations associated with familial neurodegenerative disorders on blood–brain barrier function in an iPSC model

Blood–brain barrier dysfunction is associated with many late-stage neurodegenerative diseases. An emerging question is whether the mutations associated with neurodegenerative diseases can independently lead to...

Authors: Moriah E. Katt, Lakyn N. Mayo, Shannon E. Ellis, Vasiliki Mahairaki, Jeffrey D. Rothstein, Linzhao Cheng and Peter C. Searson

Is solute movement within the extracellular spaces of brain gray matter brought about primarily by diffusion or flow? A commentary on “Analysis of convective and diffusive transport in the brain interstitium” Fluids and Barriers of the CNS (2019) 16:6 by L. Ray, J.J. Iliff and J.J. Heys

Solutes can enter and leave gray matter in the brain by perivascular routes. The glymphatic hypothesis supposes that these movements are a consequence of inward flow along periarterial spaces and an equal outw...

Authors: Stephen B. Hladky and Margery A. Barrand

In response to “Is solute movement within the extracellular spaces of brain gray matter brought about primarily by diffusion or flow?”

In our work, “Analysis of Convective and Diffusive Transport in the Brain Interstitium”, published in this journal (2019, 16:6), we estimate the interstitial superficial velocity by comparison of transport model ...

Authors: Lori Ray, Jeffrey J. Iliff and Jeffrey J. Heys

Correction to: A26 Cerebrospinal fluid outflow resistance is increased following small-moderate ischaemic stroke

After publication of this supplement [1], it was brought to our attention that in the results the line “(0.3 ± 0.04 mmHg/μl/min, and 0.54 ± 0.04 mmHg/μl/min, respectively)” should actually read “(0.54 ± 0.04 m...

Authors: Adjanie Patabendige, Nick MacKovski, Debbie Pepperall, Rebecca Hood and Neil Spratt

Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model

Immune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential ...

Authors: Shujun Ge, Xi Jiang, Debayon Paul, Li Song, Xiaofang Wang and Joel S. Pachter

Hydraulic resistance of periarterial spaces in the brain

Periarterial spaces (PASs) are annular channels that surround arteries in the brain and contain cerebrospinal fluid (CSF): a flow of CSF in these channels is thought to be an important part of the brain’s syst...

Authors: Jeffrey Tithof, Douglas H. Kelley, Humberto Mestre, Maiken Nedergaard and John H. Thomas

Abstracts from the 13th International Conference on Cerebral Vascular Biology (CVB 2019)

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A perfusion bioreactor-based 3D model of the subarachnoid space based on a meningeal tissue construct

Altered flow of cerebrospinal fluid (CSF) within the subarachnoid space (SAS) is connected to brain, but also optic nerve degenerative diseases. To overcome the lack of suitable in vitro models that faithfully...

Authors: Albert Neutzner, Laura Power, Markus Dürrenberger, Hendrik P. N. Scholl, Peter Meyer, Hanspeter E. Killer, David Wendt and Corina Kohler

Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D

Pericytes of the blood–brain barrier (BBB) are embedded within basement membrane between brain microvascular endothelial cells (BMECs) and astrocyte end-feet. Despite the direct cell–cell contact observed in v...

Authors: John J. Jamieson, Raleigh M. Linville, Yuan Yuan Ding, Sharon Gerecht and Peter C. Searson