Articles

Inhibition of transforming growth factor beta signaling pathway promotes differentiation of human induced pluripotent stem cell-derived brain microvascular endothelial-like cells

The blood–brain barrier (BBB) plays an important role as a biological barrier by regulating molecular transport between circulating blood and the brain parenchyma. In drug development, the accurate evaluation ...

Authors: Misaki Yamashita, Hiromasa Aoki, Tadahiro Hashita, Takahiro Iwao and Tamihide Matsunaga

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-e...

Authors: Peter Solár, Alemeh Zamani, Lucie Kubíčková, Petr Dubový and Marek Joukal

Measuring intracranial pressure by invasive, less invasive or non-invasive means: limitations and avenues for improvement

Sixty years have passed since neurosurgeon Nils Lundberg presented his thesis about intracranial pressure (ICP) monitoring, which represents a milestone for its clinical introduction. Monitoring of ICP has sin...

Authors: Karen Brastad Evensen and Per Kristian Eide

The incidence of significant venous sinus stenosis and cerebral hyperemia in childhood hydrocephalus: prognostic value with regards to differentiating active from compensated disease

Symptomatic or active hydrocephalus in children is linked to an elevation in intracranial pressure (ICP), which is likely to be multifactorial in origin. The CSF outflow resistance, venous sinus resistance and...

Authors: Grant Alexander Bateman, Swee Leong Yap, Gopinath Musuwadi Subramanian and Alexander Robert Bateman

Culture-induced changes in mRNA expression levels of efflux and SLC-transporters in brain endothelial cells

The complexity of the neurovascular unit (NVU) poses a challenge in the investigations of drug transport across the blood–brain barrier (BBB) and the function of the brain capillary endothelium. Several in vit...

Authors: C. Goldeman, B. Ozgür and B. Brodin

Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood–brain barrier model

The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breas...

Authors: Carolin J. Curtaz, Constanze Schmitt, Saskia-Laureen Herbert, Jonas Feldheim, Nicolas Schlegel, Fabien Gosselet, Carsten Hagemann, Norbert Roewer, Patrick Meybohm, Achim Wöckel and Malgorzata Burek

Recent advances in human iPSC-derived models of the blood–brain barrier

The blood–brain barrier (BBB) is a critical component of the central nervous system that protects neurons and other cells of the brain parenchyma from potentially harmful substances found in peripheral circula...

Authors: Michael J. Workman and Clive N. Svendsen

Intracranial pressure elevation alters CSF clearance pathways

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding ...

Authors: Vegard Vinje, Anders Eklund, Kent-Andre Mardal, Marie E. Rognes and Karen-Helene Støverud

Evidence for communication of peripheral iron status to cerebrospinal fluid: clinical implications for therapeutic strategy

Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron’s involvement in erythro...

Authors: James R. Connor, Kari Duck, Stephanie Patton, Ian A. Simpson, Lynn Marie Trotti, Richard Allen, Christopher J. Earley and David Rye

Angiomodulin (IGFBP7) is a cerebral specific angiocrine factor, but is probably not a blood–brain barrier inducer

Several secreted factors have been identified as drivers of cerebral vasculature development and inducers of blood–brain barrier (BBB) differentiation. Vascular endothelial growth factor A (VEGF-A) is central ...

Authors: Ofri Bar, Sivan Gelb, Kian Atamny, Shira Anzi and Ayal Ben-Zvi

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

Neuroimmune communication contributes to both baseline and adaptive physiological functions, as well as disease states. The vascular blood–brain barrier (BBB) and associated cells of the neurovascular unit (NV...

Authors: Michelle A. Erickson, Miranda L. Wilson and William A. Banks

Laminin 221 fragment is suitable for the differentiation of human induced pluripotent stem cells into brain microvascular endothelial-like cells with robust barrier integrity

In vitro blood–brain barrier (BBB) models using human induced pluripotent stem (iPS) cell-derived brain microvascular endothelial-like cells (iBMELCs) have been developed to predict the BBB permeability of dru...

Authors: Hiromasa Aoki, Misaki Yamashita, Tadahiro Hashita, Takahiro Iwao and Tamihide Matsunaga

Cerebrospinal fluid dynamics in non-acute post-traumatic ventriculomegaly

Post-traumatic hydrocephalus (PTH) is potentially under-diagnosed and under-treated, generating the need for a more efficient diagnostic tool. We aim to report CSF dynamics of patients with post-traumatic vent...

Authors: Afroditi D. Lalou, Virginia Levrini, Marek Czosnyka, Laurent Gergelé, Matthew Garnett, Angelos Kolias, Peter J. Hutchinson and Zofia Czosnyka

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

Authors:

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