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Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood–brain barrier Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-15 Joanna R. Thomas, William J. E. Frye, Robert W. Robey, Andrew C. Warner, Donna Butcher, Jennifer L. Matta, Tamara C. Morgan, Elijah F. Edmondson, Paula B. Salazar, Suresh V. Ambudkar, Michael M. Gottesman
A principal protective component of the mammalian blood–brain barrier (BBB) is the high expression of the multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2) on the lumenal surface of endothelial cells. The zebrafish P-gp homolog Abcb4 is expressed at the BBB and phenocopies human P-gp. Comparatively little is known about the four zebrafish homologs of
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Transient but not chronic hyperglycemia accelerates ocular glymphatic transport Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-12 Christine Delle, Xiaowei Wang, Michael Giannetto, Evan Newbold, Weiguo Peng, Ryszard Stefan Gomolka, Antonio Ladrón-de-Guevara, Neža Cankar, Elise Schiøler Nielsen, Celia Kjaerby, Pia Weikop, Yuki Mori, Maiken Nedergaard
Glymphatic transport is vital for the physiological homeostasis of the retina and optic nerve. Pathological alterations of ocular glymphatic fluid transport and enlarged perivascular spaces have been described in glaucomatous mice. It remains to be established how diabetic retinopathy, which impairs vision in about 50% of diabetes patients, impacts ocular glymphatic fluid transport. Here, we examined
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Freezing of gait in idiopathic normal pressure hydrocephalus Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-08 Carl-Johan Kihlstedt, Jan Malm, Alfonso Fasano, David Bäckström
Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study’s objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG’s responsiveness to shunt surgery. Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median
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Validating the accuracy of real-time phase-contrast MRI and quantifying the effects of free breathing on cerebrospinal fluid dynamics Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-07 Pan Liu, Kimi Owashi, Heimiri Monnier, Serge Metanbou, Cyrille Capel, Olivier Balédent
Understanding of the cerebrospinal fluid (CSF) circulation is essential for physiological studies and clinical diagnosis. Real-time phase contrast sequences (RT-PC) can quantify beat-to-beat CSF flow signals. However, the detailed effects of free-breathing on CSF parameters are not fully understood. This study aims to validate RT-PC’s accuracy by comparing it with the conventional phase-contrast sequence
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The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-04 Andrew T. Hale, Hunter Boudreau, Rishi Devulapalli, Phan Q. Duy, Travis J. Atchley, Michael C. Dewan, Mubeen Goolam, Graham Fieggen, Heather L. Spader, Anastasia A. Smith, Jeffrey P. Blount, James M. Johnston, Brandon G. Rocque, Curtis J. Rozzelle, Zechen Chong, Jennifer M. Strahle, Steven J. Schiff, Kristopher T. Kahle
Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity
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The proteome of the blood–brain barrier in rat and mouse: highly specific identification of proteins on the luminal surface of brain microvessels by in vivo glycocapture Fluids Barriers CNS (IF 7.3) Pub Date : 2024-03-04 Tammy-Lynn Tremblay, Wael Alata, Jacqueline Slinn, Ewa Baumann, Christie E. Delaney, Maria Moreno, Arsalan S. Haqqani, Danica B. Stanimirovic, Jennifer J. Hill
The active transport of molecules into the brain from blood is regulated by receptors, transporters, and other cell surface proteins that are present on the luminal surface of endothelial cells at the blood–brain barrier (BBB). However, proteomic profiling of proteins present on the luminal endothelial cell surface of the BBB has proven challenging due to difficulty in labelling these proteins in a
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Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-29 Jarrod J. Eisma, Colin D. McKnight, Kilian Hett, Jason Elenberger, Caleb J. Han, Alexander K. Song, Ciaran Considine, Daniel O. Claassen, Manus J. Donahue
The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation.
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Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-28 Diego Rossinelli, Gilles Fourestey, Hanspeter Esriel Killer, Albert Neutzner, Gianluca Iaccarino, Luca Remonda, Jatta Berberat
Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer’s and Parkinson’s disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects
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Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-26 Dipak D. Pukale, Kayla Adkins-Travis, Siddhartha R. Aryal, Leah P. Shriver, Gary J. Patti, Nic D. Leipzig
Syringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand
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Endothelial and mural laminin-α5 contributes to neurovascular integrity maintenance Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-21 Abhijit Nirwane, Minkyung Kang, Aravinthan Adithan, Vrishni Maharaj, Felicia Nguyen, Elliot Santaella Aguilar, Ava Nasrollahi, Yao Yao
Laminin-α5, a major component of the basal lamina, is predominantly synthesized by endothelial and mural cells (pericytes and vascular smooth muscle cells) in the CNS. Loss of laminin-α5 in either population fails to induce any abnormalities due to functional redundancy. Thus, the functional significance of laminin-α5 in neurovascular integrity remains unknown. Here, we hypothesize that ablation of
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Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-21 Maria Garcia-Bonilla, Alexander T. Yahanda, Albert M. Isaacs, Brandon Baksh, S. Hassan A. Akbari, Haley Botteron, Diego M. Morales, Rowland H. Han, James P. McAllister II, Amit M. Mathur, Jennifer M. Strahle, Christopher D. Smyser, David D. Limbrick
Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade
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Cerebrospinal fluid shunt surgery reduces the risk of developing dementia and Alzheimer’s disease in patients with idiopathic normal pressure hydrocephalus: a nationwide population-based propensity-weighted cohort study Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-14 Pao-Hui Tseng, Wan-Ting Huang, Jen-Hung Wang, Bor-Ren Huang, Hsin-Yi Huang, Sheng-Tzung Tsai
Patients with idiopathic normal-pressure hydrocephalus (iNPH) are predisposed to developing dementing disorders. Cerebrospinal fluid (CSF) shunt implantation is a treatment used to improve the motor and cognitive disabilities of these patients; however, its effect on the risk of developing dementing disorders remains unclear. We conducted a population-based propensity-weighted cohort study to investigate
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Deep learning segmentation of peri-sinus structures from structural magnetic resonance imaging: validation and normative ranges across the adult lifespan Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-13 Kilian Hett, Colin D. McKnight, Melanie Leguizamon, Jennifer S. Lindsey, Jarrod J. Eisma, Jason Elenberger, Adam J. Stark, Alexander K. Song, Megan Aumann, Ciaran M. Considine, Daniel O. Claassen, Manus J. Donahue
Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often
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Mass spectrometry-based proteomics of cerebrospinal fluid in pediatric central nervous system malignancies: a systematic review with meta-analysis of individual patient data Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-13 Christian Mirian, Maria Thastrup, René Mathiasen, Kjeld Schmiegelow, Jesper Velgaard Olsen, Ole Østergaard
The cerebrospinal fluid (CSF) proteome could offer important insights into central nervous system (CNS) malignancies. To advance proteomic research in pediatric CNS cancer, the current study aims to (1) evaluate past mass spectrometry-based workflows and (2) synthesize previous CSF proteomic data, focusing on both qualitative summaries and quantitative re-analysis. In our analysis of 11 studies investigating
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Analysis of the contributing role of drug transport across biological barriers in the development and treatment of chemotherapy-induced peripheral neuropathy Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-08 Yang Hu, Milda Girdenyté, Lieke Roest, Iida Liukkonen, Maria Siskou, Frida Bällgren, Margareta Hammarlund-Udenaes, Irena Loryan
Chemotherapy-induced peripheral neuropathy (CIPN) represents a major unmet medical need that currently has no preventive and/or curative treatment. This is, among others, driven by a poor understanding of the contributive role of drug transport across biological barriers to target-site exposure. Here, we systematically investigated the transport of 11 small-molecule drugs, both, associated and not
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Abstracts from Hydrocephalus 2023—the fifteenth meeting of the Hydrocephalus Society Fluids Barriers CNS (IF 7.3) Pub Date : 2024-02-02
Gianpaolo Petrella, Silvia Ciarlo, Graziano Taddei, Angelo Pompucci, Alessandro Pesce 1A.O. “Santa Maria Goretti” General Hospital, Neurosurgery Division, Latina, Italy Correspondence: Gianpaolo Petrella, gianpaolo_p@hotmail.com Fluids and Barriers of the CNS 2023, 20(Suppl 2): A1 Introduction: Idiopathic Normal Pressure Hydrocephalus (iNPH) shows a typical clinical triad consisting of gait disturbance
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Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-26 Jari Jukkola, Mika Kaakinen, Abhishek Singh, Sadegh Moradi, Hany Ferdinando, Teemu Myllylä, Vesa Kiviniemi, Lauri Eklund
Inside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect
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Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-25 Kristine Langthaler, Christopher R. Jones, Lasse Saaby, Christoffer Bundgaard, Birger Brodin
Intro: Reliable estimates of drug uptake from blood to brain parenchyma are crucial in CNS drug discovery and development. While in vivo Kp,uu,brain estimates are the gold standard for investigating brain drug disposition, animal usage is a limitation to high throughput application. This study investigates an in vitro model using P-gp expressing MDCKII-MDR1 cells for predicting in vivo brain drug penetration
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CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-25 Jonathan H. Wardman, Søren Norge Andreassen, Trine L. Toft-Bertelsen, Mette Nyholm Jensen, Jens E. Wilhjelm, Bjarne Styrishave, Steffen Hamann, Steffen Heegaard, Alexandra J. Sinclair, Nanna MacAulay
Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations
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ChOP-CT: quantitative morphometrical analysis of the Hindbrain Choroid Plexus by X-ray micro-computed tomography Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-24 Viktória Parobková, Petra Kompaníková, Jakub Lázňovský, Michaela Kavková, Marek Hampl, Marcela Buchtová, Tomáš Zikmund, Jozef Kaiser, Vítězslav Bryja
The Hindbrain Choroid Plexus is a complex, cerebrospinal fluid-secreting tissue that projects into the 4th vertebrate brain ventricle. Despite its irreplaceability in the development and homeostasis of the entire central nervous system, the research of Hindbrain Choroid Plexus and other Choroid Plexuses has been neglected by neuroscientists for decades. One of the obstacles is the lack of tools that
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Oxygen glucose deprivation-pretreated astrocyte-derived exosomes attenuates intracerebral hemorrhage (ICH)-induced BBB disruption through miR-27a-3p /ARHGAP25/Wnt/β-catenin axis Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-19 Ying Hou, Ye Xie, Xiaoxuan Liu, Yushan Chen, Fangfang Zhou, Binbin Yang
Blood brain barrier (BBB) breakdown is one of the key mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Astrocytes interact with endothelial and regulate BBB integrity via paracrine signaling factors. More and more studies reveal astrocyte-derived extracellular vesicles (ADEVs) as an important way of intercellular communication. However, the role of ADEV in BBB integrity
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Hydraulic resistance of three-dimensional pial perivascular spaces in the brain Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-11 Kimberly A. S. Boster, Jiatong Sun, Jessica K. Shang, Douglas H. Kelley, John H. Thomas
Perivascular spaces (PVSs) carry cerebrospinal fluid (CSF) around the brain, facilitating healthy waste clearance. Measuring those flows in vivo is difficult, and often impossible, because PVSs are small, so accurate modeling is essential for understanding brain clearance. The most important parameter for modeling flow in a PVS is its hydraulic resistance, defined as the ratio of pressure drop to volume
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Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-11 Vanda Tukacs, Dániel Mittli, Éva Hunyadi-Gulyás, Zsuzsanna Darula, Gábor Juhász, József Kardos, Katalin Adrienna Kékesi
The brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate
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Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-10 Rodnie Colón Ortiz, Stephen Knerler, Lisa B. Fridman, Alicia Mercado, Amira-Storm Price, Jose J. Rosado-Franco, Hannah Wilkins, Bianca R. Flores, Benjamin C. Orsburn, Dionna W. Williams
Appropriate interactions between antiretroviral therapies (ART) and drug transporters and metabolizing enzymes at the blood brain barrier (BBB) are critical to ensure adequate dosing of the brain to achieve HIV suppression. These proteins are modulated by demographic and lifestyle factors, including substance use. While understudied, illicit substances share drug transport and metabolism pathways with
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Postnatal meningeal CSF transport is primarily mediated by the arachnoid and pia maters and is not altered after intraventricular hemorrhage-posthemorrhagic hydrocephalus Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-08 Shelei Pan, Joshua P. Koleske, Gretchen M. Koller, Grace L. Halupnik, Abdul-Haq O. Alli, Shriya Koneru, Dakota DeFreitas, Sruthi Ramagiri, Jennifer M. Strahle
CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine
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Blood–brain borders: a proposal to address limitations of historical blood–brain barrier terminology Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-05 Jerome Badaut, Jean-François Ghersi-Egea, Robert G. Thorne, Jan Pieter Konsman
Many neuroscientists use the term Blood–Brain Barrier (BBB) to emphasize restrictiveness, often equating or reducing the notion of BBB properties to tight junction molecules physically sealing cerebral endothelial cells, rather than pointing out the complexity of this biological interface with respect to its selectivity and variety of exchange between the general blood circulation and the central nervous
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Sex, hormones and cerebrovascular function: from development to disorder Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-04 Adeline Collignon, Laurence Dion-Albert, Caroline Ménard, Vanessa Coelho-Santos
Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion
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Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice Fluids Barriers CNS (IF 7.3) Pub Date : 2024-01-04 Xiao J. Tong, Gokhan Akdemir, Meetu Wadhwa, Alan S. Verkman, Alex J. Smith
It has been proposed that cerebrospinal fluid (CSF) can enter and leave the retina and optic nerve along perivascular spaces surrounding the central retinal vessels as part of an aquaporin-4 (AQP4) dependent ocular ‘glymphatic’ system. Here, we injected fluorescent dextrans and antibodies into the CSF of mice at the cisterna magna and measured their distribution in the optic nerve and retina. We found
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Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-21 Ella Rowsthorn, William Pham, Mohammad-Reza Nazem-Zadeh, Meng Law, Matthew P. Pase, Ian H. Harding
The neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood–brain barrier (BBB), and supports fluid homeostasis in the brain. The integrity of NVU subcomponents can be measured in vivo using magnetic resonance imaging (MRI), including quantification of enlarged perivascular spaces (ePVS), BBB permeability, cerebral perfusion
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Characterization of an iPSC-based barrier model for blood-brain barrier investigations using the SBAD0201 stem cell line Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-19 Burak Ozgür, Elena Puris, Andreas Brachner, Antje Appelt-Menzel, Sabrina Oerter, Viktor Balzer, Mikkel Roland Holst, Rasmus Folmann Christiansen, Kathrine Hyldig, Stephen T. Buckley, Mie Kristensen, Seppo Auriola, Allan Jensen, Gert Fricker, Morten Schallburg Nielsen, Winfried Neuhaus, Birger Brodin
Blood-brain barrier (BBB) models based on primary murine, bovine, and porcine brain capillary endothelial cell cultures have long been regarded as robust models with appropriate properties to examine the functional transport of small molecules. However, species differences sometimes complicate translating results from these models to human settings. During the last decade, brain capillary endothelial-like
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Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood − brain barrier function Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-19 Baharak Hosseinkhani, Gayel Duran, Cindy Hoeks, Doryssa Hermans, Melissa Schepers, Paulien Baeten, Joren Poelmans, Britt Coenen, Kübra Bekar, Isabel Pintelon, Jean-Pierre Timmermans, Tim Vanmierlo, Luc Michiels, Niels Hellings, Bieke Broux
Autoreactive T lymphocytes crossing the blood-brain barrier (BBB) into the central nervous system (CNS) play a crucial role in the initiation of demyelination and neurodegeneration in multiple sclerosis (MS). Recently, extracellular vesicles (EV) secreted by BBB endothelial cells (BBB-EC) have emerged as a unique form of cell-to-cell communication that contributes to cerebrovascular dysfunction. However
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Methodological and analytical considerations for intra-operative microdialysis Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-19 Cecile Riviere-Cazaux, Karishma Rajani, Masum Rahman, Juhee Oh, Desmond A. Brown, Jaclyn F. White, Benjamin T. Himes, Ignacio Jusue-Torres, Moses Rodriguez, Arthur E. Warrington, Sani H. Kizilbash, William F. Elmquist, Terry C. Burns
Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight
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Structural characterization of SLYM—a 4th meningeal membrane Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-14 Virginia Plá, Styliani Bitsika, Michael J Giannetto, Antonio Ladron-de-Guevara, Daniel Gahn-Martinez, Yuki Mori, Maiken Nedergaard, Kjeld Møllgård
Traditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the brain is based on postmortem macroscopic examination. Ultrastructural and single cell transcriptome analyses have documented that the 3 meningeal layers can be subdivided into several distinct layers based on cellular characteristics
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miRNA-ome plasma analysis unveils changes in blood–brain barrier integrity associated with acute liver failure in rats Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-08 Karolina Orzeł-Gajowik, Krzysztof Milewski, Magdalena Zielińska
Hepatic encephalopathy (HE) symptoms associated with liver insufficiency are linked to the neurotoxic effects of ammonia and other toxic metabolites reaching the brain via the blood–brain barrier (BBB), further aggravated by the inflammatory response. Cumulative evidence documents that the non-coding single-stranded RNAs, micro RNAs (miRs) control the BBB functioning. However, miRs’ involvement in
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Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-06 Tomoyasu Yamanaka, Yusuke Nishikawa, Takashi Iwata, Teishiki Shibata, Mitsuru Uchida, Yuki Hayashi, Hiroyuki Katano, Motoki Tanikawa, Shigeki Yamada, Mitsuhito Mase
The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH. Overall, 204 patients (69 men and 135 women) treated for aneurysmal
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Identifying molecular tags selectively retained on the surface of brain endothelial cells to generate artificial targets for therapy delivery Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-06 Giulia Maria Porro, Italo Lorandi, Xueying Liu, Kazunori Kataoka, Giuseppe Battaglia, Daniel Gonzalez-Carter
Current strategies to identify ligands for brain delivery select candidates based on preferential binding to cell-membrane components (CMC) on brain endothelial cells (EC). However, such strategies generate ligands with inherent brain specificity limitations, as the CMC (e.g., the transferrin receptor TfR1) are also significantly expressed on peripheral EC. Therefore, novel strategies are required
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SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-05 Huixin Xu, Guillaume P. Dugué, Yasmine Cantaut-Belarif, François-Xavier Lejeune, Suhasini Gupta, Claire Wyart, Maria K. Lehtinen
Reissner’s fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the
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A metabolomics study in aqueous humor discloses altered arginine metabolism in Parkinson’s disease Fluids Barriers CNS (IF 7.3) Pub Date : 2023-12-04 Joan Serrano-Marín, Silvia Marin, David Bernal-Casas, Alejandro Lillo, Marc González-Subías, Gemma Navarro, Marta Cascante, Juan Sánchez-Navés, Rafael Franco
The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson’s disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous
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Breaking barriers: exploring mechanisms behind opening the blood–brain barrier Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-28 Melanie E. M. Stamp, Michael Halwes, David Nisbet, David J. Collins
The blood–brain barrier (BBB) is a selectively permeable membrane that separates the bloodstream from the brain. While useful for protecting neural tissue from harmful substances, brain-related diseases are difficult to treat due to this barrier, as it also limits the efficacy of drug delivery. To address this, promising new approaches for enhancing drug delivery are based on disrupting the BBB using
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Microfluidic models of the neurovascular unit: a translational view Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-27 Nienke R. Wevers, Helga E. De Vries
The vasculature of the brain consists of specialized endothelial cells that form a blood-brain barrier (BBB). This barrier, in conjunction with supporting cell types, forms the neurovascular unit (NVU). The NVU restricts the passage of certain substances from the bloodstream while selectively permitting essential nutrients and molecules to enter the brain. This protective role is crucial for optimal
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Local perfusion of capillaries reveals disrupted beta-amyloid homeostasis at the blood-brain barrier in Tg2576 murine Alzheimer’s model Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-22 Amira Sayed Hanafy, Alf Lamprecht, Dirk Dietrich
Parenchymal accumulation of beta-amyloid (Aβ) characterizes Alzheimer’s disease (AD). Aβ homeostasis is maintained by two ATP-binding cassette (ABC) transporters (ABCC1 and ABCB1) mediating efflux, and the receptor for advanced glycation end products (RAGE) mediating influx across the blood-brain barrier (BBB). Altered transporter levels and disruption of tight junctions (TJ) were linked to AD. However
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Protective effects of pyrroloquinoline quinone in brain folate deficiency Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-20 Vishal Sangha, Sara Aboulhassane, Qing Rui Qu, Reina Bendayan
Folates (Vitamin B9) are critical for normal neurodevelopment and function, with transport mediated by three major pathways: folate receptor alpha (FRα), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC). Cerebral folate uptake primarily occurs at the blood-cerebrospinal fluid barrier (BCSFB) through concerted actions of FRα and PCFT, with impaired folate transport resulting
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The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-09 Anthony Podgoršak, Nina Eva Trimmel, Markus Florian Oertel, Margarete Arras, Miriam Weisskopf, Marianne Schmid Daners
Most investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed. Six awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal
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Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-06 Mikkel Roland Holst, Nienke Marije de Wit, Burak Ozgür, Andreas Brachner, Kathrine Hyldig, Antje Appelt-Menzel, Hannah Sleven, Zameel Cader, Helga Eveline de Vries, Winfried Neuhaus, Allan Jensen, Birger Brodin, Morten Schallburg Nielsen
Here, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood–brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem cells (hiPSC-BECs) as a model system and compared them to colon epithelial Caco-2 cells. This approach helped to identify favourable receptors for transport into the cell layer
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Pathogenic mechanisms and therapeutic implications of extracellular matrix remodelling in cerebral vasospasm Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-04 Ziliang Hu, Xinpeng Deng, Shengjun Zhou, Chenhui Zhou, Menglu Shen, Xiang Gao, Yi Huang
Cerebral vasospasm significantly contributes to poor prognosis and mortality in patients with aneurysmal subarachnoid hemorrhage. Current research indicates that the pathological and physiological mechanisms of cerebral vasospasm may be attributed to the exposure of blood vessels to toxic substances, such as oxyhaemoglobin and inflammation factors. These factors disrupt cerebral vascular homeostasis
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A tissue-engineered model of the blood-tumor barrier during metastatic breast cancer Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-03 Raleigh M. Linville, Joanna Maressa, Zhaobin Guo, Tracy D. Chung, Alanna Farrell, Ria Jha, Peter C. Searson
Metastatic brain cancer has poor prognosis due to challenges in both detection and treatment. One contributor to poor prognosis is the blood–brain barrier (BBB), which severely limits the transport of therapeutic agents to intracranial tumors. During the development of brain metastases from primary breast cancer, the BBB is modified and is termed the ‘blood-tumor barrier’ (BTB). A better understanding
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Neurovascular unit disruption and blood–brain barrier leakage in MCT8 deficiency Fluids Barriers CNS (IF 7.3) Pub Date : 2023-11-03 Marina Guillén-Yunta, Víctor Valcárcel-Hernández, Ángel García-Aldea, Guadalupe Soria, José Manuel García-Verdugo, Ana Montero-Pedrazuela, Ana Guadaño-Ferraz
The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane transporter is expressed at the brain barriers, as the blood–brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8
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Human isogenic cells of the neurovascular unit exert transcriptomic cell type-specific effects on a blood-brain barrier in vitro model of late-onset Alzheimer disease Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-31 Undine Haferkamp, Carla Hartmann, Chaudhry Luqman Abid, Andreas Brachner, Alevtina Höchner, Anna Gerhartl, Bernadette Harwardt, Selin Leckzik, Jennifer Leu, Marco Metzger, Marina Nastainczyk-Wulf, Winfried Neuhaus, Sabrina Oerter, Ole Pless, Dan Rujescu, Matthias Jung, Antje Appelt-Menzel
The function of the blood-brain barrier (BBB) is impaired in late-onset Alzheimer disease (LOAD), but the associated molecular mechanisms, particularly with respect to the high-risk APOE4/4 genotype, are not well understood. For this purpose, we developed a multicellular isogenic model of the neurovascular unit (NVU) based on human induced pluripotent stem cells. The human NVU was modeled in vitro
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Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-25 Rebecca Grønning, Anna Jeppsson, Per Hellström, Katarina Laurell, Dan Farahmand, Henrik Zetterberg, Kaj Blennow, Carsten Wikkelsø, Mats Tullberg
The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. In 119 consecutive patients with iNPH, the iNPH scale was
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SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-24 Chiara Stüdle, Hideaki Nishihara, Sven Wischnewski, Laila Kulsvehagen, Sylvain Perriot, Hiroshi Ishikawa, Horst Schroten, Stephan Frank, Nikolaus Deigendesch, Renaud Du Pasquier, Lucas Schirmer, Anne-Katrin Pröbstel, Britta Engelhardt
As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood. Here, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the
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Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-24 Eline Berends, Robert J van Oostenbrugge, Sébastien Foulquier, Casper G Schalkwijk
The brain is a highly metabolically active organ requiring a large amount of glucose. Methylglyoxal (MGO), a by-product of glucose metabolism, is known to be involved in microvascular dysfunction and is associated with reduced cognitive function. Maintenance of the blood-brain barrier (BBB) is essential to maintain optimal brain function and a large amount of evidence indicates negative effects of
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Proteomic interrogation of the meninges reveals the molecular identities of structural components and regional distinctions along the CNS axis Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-19 Elise Santorella, Jeremy L. Balsbaugh, Shujun Ge, Parisa Saboori, David Baker, Joel S. Pachter
The meninges surround the brain and spinal cord, affording physical protection while also serving as a niche of neuroimmune activity. Though possessing stromal qualities, its complex cellular and extracellular makeup has yet to be elaborated, and it remains unclear whether the meninges vary along the neuroaxis. Hence, studies were carried-out to elucidate the protein composition and structural organization
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Occludin: a gatekeeper of brain Infection by HIV-1 Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-16 Silvia Torices, Leah Daire, Sierra Simon, Oandy Naranjo, Luisa Mendoza, Timea Teglas, Nikolai Fattakhov, Daniel Adesse, Michal Toborek
Compromised structure and function of the blood-brain barrier (BBB) is one of the pathological hallmarks of brain infection by HIV-1. BBB damage during HIV-1 infection has been associated with modified expression of tight junction (TJ) proteins, including occludin. Recent evidence indicated occludin as a redox-sensitive, multifunctional protein that can act as both an NADH oxidase and influence cellular
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Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-13 Madelene Braun, Gustaf Boström, Martin Ingelsson, Lena Kilander, Malin Löwenmark, Dag Nyholm, Joachim Burman, Valter Niemelä, Eva Freyhult, Kim Kultima, Johan Virhammar
Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients
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In vitro investigation of the effect of proinflammatory cytokines on mouse choroid plexus membrane transporters Ncbe and NKCC1 Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-12 Laura Øllegaard Johnsen, Kathrine Abildskov Friis, Helle Hasager Damkier
Intraventricular hemorrhage is a potentially life-threatening condition. Approximately 20% of patients develop posthemorrhagic hydrocephalus with increased ventricular volume and intracranial pressure. Hydrocephalus develops partially due to increased secretion of cerebrospinal fluid by the choroid plexus. During hemorrhage a multitude of factors are released into the cerebrospinal fluid. Many of these
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Proteasome inhibition protects blood–brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer’s disease model Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-06 Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz
Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating
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Transient intracranial pressure elevations (B waves) are associated with sleep apnea Fluids Barriers CNS (IF 7.3) Pub Date : 2023-10-02 Casper Schwartz Riedel, Isabel Martinez-Tejada, Morten Andresen, Jens E. Wilhjelm, Poul Jennum, Marianne Juhler
Repetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies
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Blood-spinal cord barrier disruption in degenerative cervical myelopathy Fluids Barriers CNS (IF 7.3) Pub Date : 2023-09-25 Hyun Woo Kim, Hu Yong, Graham Ka Hon Shea
Degenerative cervical myelopathy (DCM) is the most prevalent cause of spinal cord dysfunction in the aging population. Significant neurological deficits may result from a delayed diagnosis as well as inadequate neurological recovery following surgical decompression. Here, we review the pathophysiology of DCM with an emphasis on how blood-spinal cord barrier (BSCB) disruption is a critical yet neglected
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BBB opening by low pulsed electric fields, depicted by delayed-contrast MRI, enables efficient delivery of therapeutic doxorubicin doses into mice brains Fluids Barriers CNS (IF 7.3) Pub Date : 2023-09-22 Itzik Cooper, David Last, Orly Ravid, Daniel Rand, Erez Matsree, Liora Omesi, Chen Shemesh, Meir Liberman, Leor Zach, Orit Furman, Dianne Daniels, Sigal Liraz-Zaltsman, Yael Mardor, Shirley Sharabi
Pharmacological treatment of CNS diseases is limited due to the presence of the blood-brain barrier (BBB). Recent years showed significant advancement in the field of CNS drug delivery enablers, with technologies such as MR-guided focused ultrasound reaching clinical trials. This have inspired researchers in the field to invent novel brain barriers opening (BBo) technologies that are required to be
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Proteomic alterations in the brain and blood–brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer’s disease Fluids Barriers CNS (IF 7.3) Pub Date : 2023-09-14 Shingo Ito, Ryotaro Yagi, Seiryo Ogata, Takeshi Masuda, Takashi Saito, Takaomi Saido, Sumio Ohtsuki
Blood–brain barrier (BBB) dysfunction is supposed to be an early event in the development of Alzheimer’s disease (AD). This study aimed to investigate the relationship between BBB alterations and AD progression in terms of amyloid-β peptide (Aβ) accumulation in the brains of humanized amyloid precursor protein knock-in (APP-KI) mice. Brain Aβ accumulation was examined using immunohistochemical analysis