Articles

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017

This is a report on the CNS barrier congress held in London, UK, March 22–23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes,...

Authors: John Greenwood, Margareta Hammarlund-Udenaes, Hazel C. Jones, Alan W. Stitt, Roosmarijn E. Vandenbroucke, Ignacio A. Romero, Matthew Campbell, Gert Fricker, Birger Brodin, Heiko Manninga, Pieter J. Gaillard, Markus Schwaninger, Carl Webster, Krzysztof B. Wicher and Michel Khrestchatisky

Revisiting atenolol as a low passive permeability marker

Atenolol, a hydrophilic beta blocker, has been used as a model drug for studying passive permeability of biological membranes such as the blood–brain barrier (BBB) and the intestinal epithelium. However, the e...

Authors: Xiaomei Chen, Tim Slättengren, Elizabeth C. M. de Lange, David E. Smith and Margareta Hammarlund-Udenaes

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

Authors: Andrzej Małecki, Janina Skipor-Lahuta, Michal Toborek, N. Joan Abbott, David A. Antonetti, Enming Joe Su, Daniel A. Lawrence, Müge Atış, Uğur Akcan, Canan Uğur Yılmaz, Nurcan Orhan, Poyraz Düzgün, Umut Deniz Ceylan, Nadir Arıcan, Serçin Karahüseyinoğlu, Gizem Nur Şahin…

Hyperdynamic CSF motion profiles found in idiopathic normal pressure hydrocephalus and Alzheimer’s disease assessed by fluid mechanics derived from magnetic resonance images

Magnetic resonance imaging (MRI) does not only ascertain morphological features, but also measures physiological properties such as fluid velocity or pressure gradient. The purpose of this study was to investi...

Authors: Ken Takizawa, Mitsunori Matsumae, Naokazu Hayashi, Akihiro Hirayama, Satoshi Yatsushiro and Kagayaki Kuroda

Correction to: Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses

After publication of the article [1], it has been brought to our attention that the full funding acknowledgement is missing from the original article.

Authors: Amauri Dalla Corte, Carolina F. M. de Souza, Maurício Anés, Fabio K. Maeda, Armelle Lokossou, Leonardo M. Vedolin, Maria Gabriela Longo, Monica M. Ferreira, Solanger G. P. Perrone, Olivier Balédent and Roberto Giugliani

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency

Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall...

Authors: Edit Dósa, Krisztina Heltai, Tamás Radovits, Gabriella Molnár, Judit Kapocsi, Béla Merkely, Rongwei Fu, Nancy D. Doolittle, Gerda B. Tóth, Zachary Urdang and Edward A. Neuwelt

Characterization of cardiac- and respiratory-driven cerebrospinal fluid motion based on asynchronous phase-contrast magnetic resonance imaging in volunteers

A classification of cardiac- and respiratory-driven components of cerebrospinal fluid (CSF) motion has been demonstrated using echo planar imaging and time-spatial labeling inversion pulse techniques of magnet...

Authors: Ken Takizawa, Mitsunori Matsumae, Saeko Sunohara, Satoshi Yatsushiro and Kagayaki Kuroda

Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses

Very little is known about the incidence and prevalence of hydrocephalus in patients with mucopolysaccharidoses (MPS). The biggest challenge is to distinguish communicating hydrocephalus from ventricular dilat...

Authors: Amauri Dalla Corte, Carolina F. M. de Souza, Maurício Anés, Fabio K. Maeda, Armelle Lokossou, Leonardo M. Vedolin, Maria Gabriela Longo, Monica M. Ferreira, Solanger G. P. Perrone, Olivier Balédent and Roberto Giugliani

The role of perfusion and diffusion MRI in the assessment of patients affected by probable idiopathic normal pressure hydrocephalus. A cohort-prospective preliminary study

Invasive tests measuring resistance to cerebral spinal fluid (CSF) outflow and the effect of temporary drainage of CSF are used to select candidates affected by idiopathic normal pressure hydrocephalus (iNPH) ...

Authors: Francesco Tuniz, Maria Caterina Vescovi, Daniele Bagatto, Daniela Drigo, Maria Cristina De Colle, Marta Maieron and Miran Skrap

Profiling of metalloprotease activities in cerebrospinal fluids of patients with neoplastic meningitis

Neoplastic invasion into leptomeninges and subarachnoid space, resulting in neoplastic meningitis (NM) is a fatal complication of advanced solid and hematological neoplasms. Identification of malignant involve...

Authors: Catharina Conrad, Kristina Dorzweiler, Miles A. Miller, Douglas A. Lauffenburger, Herwig Strik and Jörg W. Bartsch

Erratum to: The Wisconsin Hydrocephalus Survey: shunt-dependent hydrocephalus management style among members of the American Society of Pediatric Neurosurgeons

Authors: Mark Richard Kraemer and Bermans J. Iskandar

Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs)

The endothelial cells that form the lumen of capillaries and microvessels are an important component of the blood–brain barrier. Cell phenotype is regulated by transducing a range of biomechanical and biochemi...

Authors: Jackson G. DeStefano, Zinnia S. Xu, Ashley J. Williams, Nahom Yimam and Peter C. Searson

Blood–brain barrier and foetal-onset hydrocephalus, with a view on potential novel treatments beyond managing CSF flow

Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow...

Authors: M. Guerra, J. L. Blázquez and E. M. Rodríguez

Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. T...

Authors: Grant A. Bateman, Jeannette Lechner-Scott, Ross Copping, Christopher Moeskops and Swee Leong Yap

Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation

Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P _dural ). In the upright posture, P

Authors: Petter Holmlund, Elias Johansson, Sara Qvarlander, Anders Wåhlin, Khalid Ambarki, Lars-Owe D. Koskinen, Jan Malm and Anders Eklund

Abstracts from Hydrocephalus 2016

Authors: A. Adam, J. Robison, J. Lu, R. Jose, N. Badran, T. Vivas-Buitrago, D. Rigamonti, A. Sattar, O. Omoush, M. Hammad, M. Dawood, M. Maghaslah, T. Belcher, K. Carson, J. Hoffberger, I. Jusué Torres…

Patterns of relapse in primary central nervous system lymphoma: inferences regarding the role of the neuro-vascular unit and monoclonal antibodies in treating occult CNS disease

The radiologic features and patterns of primary central nervous system lymphoma (PCNSL) at initial presentation are well described. High response rates can be achieved with first-line high-dose methotrexate (H...

Authors: Prakash Ambady, Rongwei Fu, Joao Prola Netto, Cymon Kersch, Jenny Firkins, Nancy D. Doolittle and Edward A. Neuwelt

Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase

Cerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured prot...

Authors: Mahdi Asgari, Diane A. de Zélicourt and Vartan Kurtcuoglu

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagn...

Authors: Zhongyun Chen, Chunyan Liu, Jie Zhang, Norman Relkin, Yan Xing and Yanfeng Li

NIH workshop report on the trans-agency blood–brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface

A trans-agency workshop on the blood–brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Departm...

Authors: Margaret J. Ochocinska, Berislav V. Zlokovic, Peter C. Searson, A. Tamara Crowder, Richard P. Kraig, Julia Y. Ljubimova, Todd G. Mainprize, William A. Banks, Ronald Q. Warren, Andrei Kindzelski, William Timmer and Christina H. Liu

Cerebrospinal fluid (CSF) biomarkers of iron status are associated with CSF viral load, antiretroviral therapy, and demographic factors in HIV-infected adults

HIV-associated neurocognitive disorder (HAND) remains common, despite antiretroviral therapy (ART). HIV dysregulates iron metabolism, but cerebrospinal fluid (CSF) levels of iron and iron-transport proteins in...

Authors: Stephanie M. Patton, Quan Wang, Todd Hulgan, James R. Connor, Peilin Jia, Zhongming Zhao, Scott L. Letendre, Ronald J. Ellis, William S. Bush, David C. Samuels, Donald R. Franklin, Harpreet Kaur, Jennifer Iudicello, Igor Grant and Asha R. Kallianpur

Frontotemporal dementia as a comorbidity to idiopathic normal pressure hydrocephalus (iNPH): a short review of literature and an unusual case

Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present with similar symptoms. These include decline in executive...

Authors: V. E. Korhonen, E. Solje, N. M. Suhonen, T. Rauramaa, R. Vanninen, A. M. Remes and V. Leinonen

Accelerated differentiation of human induced pluripotent stem cells to blood–brain barrier endothelial cells

Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular e...

Authors: Emma K. Hollmann, Amanda K. Bailey, Archit V. Potharazu, M. Diana Neely, Aaron B. Bowman and Ethan S. Lippmann

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

While the impact of hemorrhagic and ischemic strokes on the blood–brain barrier has been extensively studied, the impact of these types of stroke on the choroid plexus, site of the blood-CSF barrier, has recei...

Authors: Jianming Xiang, Lisa J. Routhe, D. Andrew Wilkinson, Ya Hua, Torben Moos, Guohua Xi and Richard F. Keep

Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis

Meningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in...

Authors: Marija Djukic, Ralf Trimmel, Ingelore Nagel, Annette Spreer, Peter Lange, Christine Stadelmann and Roland Nau

Nrf2 signaling increases expression of ATP-binding cassette subfamily C mRNA transcripts at the blood–brain barrier following hypoxia-reoxygenation stress

Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resista...

Authors: Kathryn Ibbotson, Joshua Yell and Patrick T. Ronaldson

Is posture-related craniospinal compliance shift caused by jugular vein collapse? A theoretical analysis

Postural changes are related to changes in cerebrospinal fluid (CSF) dynamics. While sitting up leads to a decrease in cranial CSF pressure, it also causes shifts in the craniospinal CSF volume and compliance ...

Authors: Manuel Gehlen, Vartan Kurtcuoglu and Marianne Schmid Daners

The MRZ reaction in primary progressive multiple sclerosis

The MRZ reaction (MRZR), composed of the three antibody indices (AI) against measles, rubella and varicella zoster virus and found positive in the majority of relapsing-remitting multiple sclerosis (RRMS) pati...

Authors: Tilman Hottenrott, Rick Dersch, Benjamin Berger, Sebastian Rauer, Daniela Huzly and Oliver Stich

Brain barriers and brain fluid research in 2016: advances, challenges and controversies

This editorial highlights some of the advances that occurred in relation to brain barriers and brain fluid research in 2016. It also aims to raise some of the attendant controversies and challenges in such res...

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

A change in brain white matter after shunt surgery in idiopathic normal pressure hydrocephalus: a tract-based spatial statistics study

The aim of this study was to elucidate changes in cerebral white matter after shunt surgery in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI).

Authors: Shigenori Kanno, Makoto Saito, Tomohito Kashinoura, Yoshiyuki Nishio, Osamu Iizuka, Hirokazu Kikuchi, Masahito Takagi, Masaki Iwasaki, Shoki Takahashi and Etsuro Mori

Permeability across a novel microfluidic blood-tumor barrier model

The lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the ...

Authors: Tori B. Terrell-Hall, Amanda G. Ammer, Jessica I. G. Griffith and Paul R. Lockman

Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab

Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast mag...

Authors: Joao Prola Netto, Daniel Schwartz, Csanad Varallyay, Rongwei Fu, Bronwyn Hamilton and Edward A. Neuwelt

Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain

Uric acid (UA) is known to exert neuroprotective effects in the brain. However, the mechanism of UA regulation in the brain is not well characterized. In our previous study, we described that the mouse urate t...

Authors: Naoko H. Tomioka, Yoshifuru Tamura, Tappei Takada, Shigeru Shibata, Hiroshi Suzuki, Shunya Uchida and Makoto Hosoyamada

Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers

Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dep...

Authors: Aaron Dadas, Jolewis Washington, Nicola Marchi and Damir Janigro

Early and delayed assessments of quantitative gait measures to improve the tap test as a predictor of shunt effectiveness in idiopathic normal pressure hydrocephalus

To improve the diagnostic performance of the cerebrospinal fluid (CSF) tap test (TT), early and delayed assessments of gait were performed after the removal of 30 ml of CSF in patients with probable idiopathic...

Authors: Masatsune Ishikawa, Shigeki Yamada and Kazuo Yamamoto

Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles

The two major interfaces separating brain and blood have different primary roles. The choroid plexuses secrete cerebrospinal fluid into the ventricles, accounting for most net fluid entry to the brain. Aquapor...

Authors: Stephen B. Hladky and Margery A. Barrand

Cerebral hypoxia/ischemia selectively disrupts tight junctions complexes in stem cell-derived human brain microvascular endothelial cells

Cerebral hypoxia/ischemia (H/I) is an important stress factor involved in the disruption of the blood–brain barrier (BBB) following stroke injury, yet the cellular and molecular mechanisms on how the human BBB...

Authors: Shyanne Page, Alli Munsell and Abraham J. Al-Ahmad

A comparison between the pathophysiology of multiple sclerosis and normal pressure hydrocephalus: is pulse wave encephalopathy a component of MS?

It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matte...

Authors: Grant A. Bateman, Jeannette Lechner-Scott and Rodney A. Lea

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have...

Authors: Simon McArthur, Rodrigo Azevedo Loiola, Elisa Maggioli, Mariella Errede, Daniela Virgintino and Egle Solito

Small cisterno-lumbar gradient of phosphorylated Tau protein in geriatric patients with suspected normal pressure hydrocephalus

The composition of the cerebrospinal fluid (CSF) is not homogeneous, and concentrations of proteins from different origins diverge among ventricular, cisternal and lumbar CSF fractions. Concentrations of blood...

Authors: Marija Djukic, Annette Spreer, Peter Lange, Stephanie Bunkowski, Jens Wiltfang and Roland Nau

Inhibition of ADAM10 promotes the clearance of Aβ across the BBB by reducing LRP1 ectodomain shedding

Transport across the blood–brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer’s disease (AD). One of the rece...

Authors: B. Shackleton, F. Crawford and C. Bachmeier

Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus

Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) and α- and β-cleaved soluble forms of amyloid precursor protein (sAPPα and ...

Authors: A. Jeppsson, Mikko Höltta, H. Zetterberg, K. Blennow, C. Wikkelsø and Mats Tullberg

In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)

Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concent...

Authors: Erin Gallagher, Il Minn, Janice E. Chambers and Peter C. Searson

Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting

Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the b...

Authors: Martin J. Schmidt, Christoph Rummel, Jessica Hauer, Malgorzata Kolecka, Nele Ondreka, Vanessa McClure and Joachim Roth

Directional cerebrospinal fluid movement between brain ventricles in larval zebrafish

Cerebrospinal fluid (CSF) contained within the brain ventricles contacts neuroepithelial progenitor cells during brain development. Dynamic properties of CSF movement may limit locally produced factors to spec...

Authors: Ryann M. Fame, Jessica T. Chang, Alex Hong, Nicole A. Aponte-Santiago and Hazel Sive

Diffusion tensor imaging with direct cytopathological validation: characterisation of decorin treatment in experimental juvenile communicating hydrocephalus

In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculom...

Authors: Anuriti Aojula, Hannah Botfield, James Patterson McAllister II, Ana Maria Gonzalez, Osama Abdullah, Ann Logan and Alexandra Sinclair

MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro

Increased leukocyte adhesion to brain endothelial cells forming the blood–brain barrier (BBB) precedes extravasation into the central nervous system (CNS) in neuroinflammatory diseases such as multiple scleros...

Authors: Camilla Cerutti, Patricia Soblechero-Martin, Dongsheng Wu, Miguel Alejandro Lopez-Ramirez, Helga de Vries, Basil Sharrack, David Kingsley Male and Ignacio Andres Romero

Magnesium sulfate treatment for juvenile ferrets following induction of hydrocephalus with kaolin

Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO₄). We hypothesized that MgSO₄ therapy would improve outcomes...

Authors: Domenico L. Di Curzio, Emily Turner-Brannen, Xiaoyan Mao and Marc R. Del Bigio

Growth-factor reduced Matrigel source influences stem cell derived brain microvascular endothelial cell barrier properties

Patient-derived induced pluripotent stem cells (iPSCs) are an innovative source as an in vitro model for neurological diseases. Recent studies have demonstrated the differentiation of brain microvascular endot...

Authors: Ronak Patel and Abraham J. Alahmad

Evolutionary development of embryonic cerebrospinal fluid composition and regulation: an open research field with implications for brain development and function

Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, ...

Authors: David Bueno and Jordi Garcia-Fernàndez