Articles

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

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 ro...

Authors: Stephen B. Hladky and Margery A. Barrand

Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis

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...

Authors: Mariella Errede, Domenica Mangieri, Giovanna Longo, Francesco Girolamo, Ignazio de Trizio, Antonella Vimercati, Gabriella Serio, Karl Frei, Roberto Perris and Daniela Virgintino

Cerebral influx of Na⁺ and Cl⁻ as the osmotherapy-mediated rebound response in rats

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 ex...

Authors: Eva Kjer Oernbo, Kasper Lykke, Annette Buur Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher and Nanna MacAulay

Blood–brain and blood–cerebrospinal fluid barrier permeability in spontaneously hypertensive rats

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 oedem...

Authors: Daphne M. P. Naessens, Judith de Vos, Ed VanBavel and Erik N. T. P. Bakker

The role of plasmalemma vesicle-associated protein in pathological breakdown of blood–brain and blood–retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema

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...

Authors: Esmeralda K. Bosma, Cornelis J. F. van Noorden, Reinier O. Schlingemann and Ingeborg Klaassen

Sex-specific differences in organic anion transporting polypeptide 1a4 (Oatp1a4) functional expression at the blood–brain barrier in Sprague–Dawley rats

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...

Authors: Hrvoje Brzica, Wazir Abdullahi, Bianca G. Reilly and Patrick T. Ronaldson

A perfused human blood–brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport

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 hig...

Authors: 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 and Birgit Obermeier

Accurate, strong, and stable reporting of choroid plexus epithelial cells in transgenic mice using a human transthyretin BAC

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 ar...

Authors: Brett A. Johnson, Margaret Coutts, Hillary M. Vo, Xinya Hao, Nida Fatima, Maria J. Rivera, Robert J. Sims, Michael J. Neel, Young-Jin Kang and Edwin S. Monuki

Characteristics of the cerebrospinal fluid pressure waveform and craniospinal compliance in idiopathic intracranial hypertension subjects

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 t...

Authors: Monica D. Okon, Cynthia J. Roberts, Ashraf M. Mahmoud, Andrew N. Springer, Robert H. Small, John M. McGregor and Steven E. Katz

Pulsatile flow drivers in brain parenchyma and perivascular spaces: a resistance network model study

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 ...

Authors: Julian Rey and Malisa Sarntinoranont

Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

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 lipi...

Authors: Servio H. Ramirez, Allison M. Andrews, Debayon Paul and Joel S. Pachter

Is bulk flow plausible in perivascular, paravascular and paravenous channels?

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 hav...

Authors: Mohammad M. Faghih and M. Keith Sharp

Challenges in cerebrospinal fluid shunting in patients with glioblastoma

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 glio...

Authors: Bujung Hong, Manolis Polemikos, Hans E. Heissler, Christian Hartmann, Makoto Nakamura and Joachim K. Krauss

Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

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 prov...

Authors: 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 and Conrad E. Johanson

Zika virus crosses an in vitro human blood brain barrier model

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 st...

Authors: Judie B. Alimonti, Maria Ribecco-Lutkiewicz, Caroline Sodja, Anna Jezierski, Danica B. Stanimirovic, Qing Liu, Arsalan S. Haqqani, Wayne Conlan and Mahmud Bani-Yaghoub

Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus

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 nimodipi...

Authors: Domenico L. Di Curzio, Xiaoyan Mao, Aidan Baker and Marc R. Del Bigio

Fluid outflow in the rat spinal cord: the role of perivascular and paravascular pathways

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. A...

Authors: Shinuo Liu, Magdalena A. Lam, Alisha Sial, Sarah J. Hemley, Lynne E. Bilston and Marcus A. Stoodley

Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models

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 transp...

Authors: Midrelle E. Noumbissi, Bianca Galasso and Monique F. Stins

Modeling and rescue of defective blood–brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brai...

Authors: Catherine A. A. Lee, Hannah S. Seo, Anibal G. Armien, Frank S. Bates, Jakub Tolar and Samira M. Azarin

Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop

The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on July 25 and 26, 2016 at the National Institutes of Health. The workshop brought together a diverse group of researchers includin...

Authors: Jenna E. Koschnitzky, Richard F. Keep, David D. Limbrick Jr., James P. McAllister II, Jill A. Morris, Jennifer Strahle and Yun C. Yung

Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Many studies have focused on the challenges of small molecule uptake across the blood–brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central ner...

Authors: Qin Wang, Luisette Delva, Paul H. Weinreb, Robert B. Pepinsky, Danielle Graham, Elvana Veizaj, Anne E. Cheung, Weiping Chen, Ivan Nestorov, Ellen Rohde, Robin Caputo, Geoffrey M. Kuesters, Tonika Bohnert and Liang-Shang Gan

Cerebrospinal fluid protein and glucose levels in neonates with a systemic inflammatory response without meningitis

It has been estimated that paediatric meningitis without elevated CSF white cell count (pleocytosis) accounts for 0.5–12% of all cases of bacterial meningitis. CSF protein and glucose measurements are therefor...

Authors: Mona Noureldein, Roxana Mardare, Jack Pickard, Hoi Lun Shing and Michael Eisenhut

Functional brain-specific microvessels from iPSC-derived human brain microvascular endothelial cells: the role of matrix composition on monolayer formation

Transwell-based models of the blood–brain barrier (BBB) incorporating monolayers of human brain microvascular endothelial cells (dhBMECs) derived from induced pluripotent stem cells show many of the key featur...

Authors: Moriah E. Katt, Raleigh M. Linville, Lakyn N. Mayo, Zinnia S. Xu and Peter C. Searson

Paradigm-shift: radiological changes in the asymptomatic iNPH-patient to be: an observational study

Many radiological signs are known for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). However, there is little information about these signs in the pre-symptomatic phase. For pathophysiologic...

Authors: D. C. Engel, S. D. Adib, M. U. Schuhmann and C. Brendle

Progress in brain barriers and brain fluid research in 2017

The past year, 2017, has seen many important papers published in the fields covered by Fluids and Barriers of the CNS. This article from the Editors highlights some.

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

Hydrocephalus 2017, the Ninth Annual Meeting of the International Society for Hydrocephalus and CSF disorders (Hydrocephalus Society)

Authors:

The effect of an adenosine A_2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma

The blood–brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A_2A receptors causes transient BBB d...

Authors: Sadhana Jackson, Jon Weingart, Edjah K. Nduom, Thura T. Harfi, Richard T. George, Dorothea McAreavey, Xiaobu Ye, Nicole M. Anders, Cody Peer, William D. Figg, Mark Gilbert, Michelle A. Rudek and Stuart A. Grossman

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

After publication of the article [1], it has been brought to our attention that there are some errors in the formatting of names in the final version of the article.

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

Role of cationic drug-sensitive transport systems at the blood-cerebrospinal fluid barrier in para-tyramine elimination from rat brain

para-Tyramine (p-TA) is a biogenic amine which is involved in multiple neuronal signal transductions. Since the concentration of p-TA in dog cerebrospinal fluid (CSF) has been reported to be ...

Authors: Shin-ichi Akanuma, Yuhei Yamazaki, Yoshiyuki Kubo and Ken-ichi Hosoya

A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets

The spinal subarachnoid space (SSS) has a complex 3D fluid-filled geometry with multiple levels of anatomic complexity, the most salient features being the spinal cord and dorsal and ventral nerve rootlets. An...

Authors: Lucas R. Sass, Mohammadreza Khani, Gabryel Connely Natividad, R. Shane Tubbs, Olivier Baledent and Bryn A. Martin

Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus

Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebros...

Authors: Gakwaya Habiyaremye, Diego M. Morales, Clinton D. Morgan, James P. McAllister, Travis S. CreveCoeur, Rowland H. Han, Mohamed Gabir, Brandon Baksh, Deanna Mercer and David D. Limbrick Jr.

Do patients with schizophreniform and bipolar disorders show an intrathecal, polyspecific, antiviral immune response? A pilot study

We previously described inflammatory cerebrospinal fluid (CSF) alterations in a subgroup of patients with schizophreniform disorders and the synthesis of polyspecific intrathecal antibodies against different n...

Authors: Dominique Endres, Daniela Huzly, Rick Dersch, Oliver Stich, Benjamin Berger, Florian Schuchardt, Evgeniy Perlov, Nils Venhoff, Sabine Hellwig, Bernd L. Fiebich, Daniel Erny, Tilman Hottenrott and Ludger Tebartz van Elst

The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse

Opioids are currently the primary treatment method used to manage both acute and chronic pain. In the past two to three decades, there has been a surge in the use, abuse and misuse of opioids. The mechanism by...

Authors: Charles P. Schaefer, Margaret E. Tome and Thomas P. Davis

LDL receptor blockade reduces mortality in a mouse model of ischaemic stroke without improving tissue-type plasminogen activator-induced brain haemorrhage: towards pre-clinical simulation of symptomatic ICH

Symptomatic intracerebral haemorrhage (sICH) following tissue-type plasminogen activator (rt-PA) administration is the most feared and lethal complication of thrombolytic therapy for ischaemic stroke, creating...

Authors: Be’eri Niego, Brad R. S. Broughton, Heidi Ho, Christopher G. Sobey and Robert L. Medcalf

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…