The blood–brain barrier in health and disease: Important unanswered questions

Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction

(2019) Daniel A. Nation et al.   NATURE MEDICINE

Astrocytic endfeet re-cover blood vessels after removal by laser ablation

(2019) Hideaki Kubotera et al.   Scientific Reports

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

(2019) Marta Joana Costa Jordão et al.   SCIENCE

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

(2019) Takahiro Masuda et al.   NATURE

Endothelial Adora2a activation promotes blood-brain barrier breakdown and cognitive impairment in mice with diet-induced insulin resistance

(2019) Masaki Yamamoto et al.   JOURNAL OF NEUROSCIENCE

Blood-brain barrier permeability and physical exercise

(2019) Marta A. Małkiewicz et al.   Journal of Neuroinflammation

Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1

(2019) Hanadie Yousef et al.   NATURE MEDICINE

Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures

(2019) Yanshu Wang et al.   eLife

Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice

(2019) Fabienne Benz et al.   eLife

Macrophages at CNS interfaces: ontogeny and function in health and disease

(2019) Katrin Kierdorf et al.   NATURE REVIEWS NEUROSCIENCE

Regulation of the Blood–Brain Barrier by Circadian Rhythms and Sleep

(2019) Vishnu Anand Cuddapah et al.   TRENDS IN NEUROSCIENCES

PECAM-1 Stabilizes Blood-Brain Barrier Integrity and Favors Paracellular T-Cell Diapedesis Across the Blood-Brain Barrier During Neuroinflammation

(2019) Isabella Wimmer et al.   Frontiers in Immunology

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

(2019) Stephen B. Hladky et al.   Fluids and Barriers of the CNS

Glymphatics visualization after focused ultrasound induced blood‐brain barrier opening in humans

(2019) Ying Meng et al.   ANNALS OF NEUROLOGY

Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module

(2019) Roeben Nocon Munji et al.   NATURE NEUROSCIENCE

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

(2019) Nina E. Fultz et al.   SCIENCE

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

(2018) N. Joan Abbott et al.   ACTA NEUROPATHOLOGICA

A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux

(2018) Shirley L. Zhang et al.   CELL

High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease

(2018) Dunja Mrdjen et al.   IMMUNITY

Markers for human brain pericytes and smooth muscle cells

(2018) Leon C.D. Smyth et al.   JOURNAL OF CHEMICAL NEUROANATOMY

Male and Female Mice Exhibit Divergent Responses of the Cortical Vasculature to Traumatic Brain Injury

(2018) Amandine Jullienne et al.   JOURNAL OF NEUROTRAUMA

Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics

(2018) Mark A. Petersen et al.   NATURE REVIEWS NEUROSCIENCE

IL-1β enables CNS access to CCR2himonocytes and the generation of pathogenic cells through GM-CSF released by CNS endothelial cells

(2018) Alexandre Paré et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ICAM-1null C57BL/6 Mice Are Not Protected from Experimental Ischemic Stroke

(2018) Gaby U. Enzmann et al.   Translational Stroke Research

Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?

(2018) Brian DellaValle et al.   Frontiers in Immunology

Evidence for peri-ictal blood–brain barrier dysfunction in patients with epilepsy

(2018) Theodor Rüber et al.   BRAIN

Evidence for sex difference in the CSF/plasma albumin ratio in ~20 000 patients and 335 healthy volunteers

(2018) Cristina Parrado-Fernández et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

A lymphatic waste-disposal system implicated in Alzheimer’s disease

(2018) Melanie D. Sweeney et al.   NATURE

Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease

(2018) Sandro Da Mesquita et al.   NATURE

A molecular atlas of cell types and zonation in the brain vasculature

(2018) Michael Vanlandewijck et al.   NATURE

Gelatinase B/matrix metalloproteinase-9 is a phase-specific effector molecule, independent from Fas, in experimental autoimmune encephalomyelitis

(2018) Estefania Ugarte-Berzal et al.   PLoS One

Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood–brain barrier

(2018) Nikolay Kutuzov et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The glymphatic pathway in neurological disorders

(2018) Martin Kaag Rasmussen et al.   LANCET NEUROLOGY

Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance

(2018) Yanshu Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier

(2018) Yoshiaki Ando et al.   Scientific Reports

Aquaporin-4-dependent glymphatic solute transport in the rodent brain

(2018) Humberto Mestre et al.   eLife

Glycocalyx degradation leads to blood–brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats

(2017) Jiajia Zhu et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Gpr124 is essential for blood–brain barrier integrity in central nervous system disease

(2017) Junlei Chang et al.   NATURE MEDICINE

Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

(2017) Sinisa Hrvatin et al.   NATURE NEUROSCIENCE

The choroid plexus in health and in disease: dialogues into and out of the brain

(2017) Fernanda Marques et al.   NEUROBIOLOGY OF DISEASE

Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation

(2017) Chris Cho et al.   NEURON

Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis

(2017) Benjamin J. Andreone et al.   NEURON

Gradual Suppression of Transcytosis Governs Functional Blood-Retinal Barrier Formation

(2017) Brian Wai Chow et al.   NEURON

Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis

(2017) Marc-André Lécuyer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

(2017) Samantha J. Hindle et al.   Cell Reports

Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

(2017) Sarah E. Lutz et al.   Cell Reports

Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration

(2017) Jian Song et al.   Cell Reports

P-glycoprotein Function in the Rodent Brain Displays a Daily Rhythm, a Quantitative In Vivo PET Study

(2016) Heli Savolainen et al.   AAPS Journal

Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking

(2016) E. Maggioli et al.   BRAIN BEHAVIOR AND IMMUNITY

Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder

(2016) Dora C. Tărlungeanu et al.   CELL

Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier

(2016) Norman R. Saunders et al.   Developmental Neurobiology

Age-associated physiological and pathological changes at the blood–brain barrier: A review

(2016) Franciska Erdő et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke

(2016) D. Fernandez-Lopez et al.   JOURNAL OF NEUROSCIENCE

A 40 Reduces P-Glycoprotein at the Blood-Brain Barrier through the Ubiquitin-Proteasome Pathway

(2016) A. M. S. Hartz et al.   JOURNAL OF NEUROSCIENCE

Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid

(2016) Christian Schläger et al.   NATURE

Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles

(2016) Anusha Mishra et al.   NATURE NEUROSCIENCE

Solute Carriers in the Blood–Brain Barier: Safety in Abundance

(2016) Katarzyna A. Nałęcz   NEUROCHEMICAL RESEARCH

Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier

(2016) Nanhong Lou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

(2016) Harm J. van de Haar et al.   RADIOLOGY

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

(2016) Deepak Kumar Vijaya Kumar et al.   Science Translational Medicine

Melanoma cell adhesion molecule-positive CD8 T lymphocytes mediate central nervous system inflammation

(2015) Catherine Larochelle et al.   ANNALS OF NEUROLOGY

Regulation of ABC transporters at the blood-brain barrier

(2015) DS Miller   CLINICAL PHARMACOLOGY & THERAPEUTICS

Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood-brain barrier

(2015) Michael Abadier et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation

(2015) Fabien Sohet et al.   JOURNAL OF CELL BIOLOGY

Brain barriers: Crosstalk between complex tight junctions and adherens junctions

(2015) Silvia Tietz et al.   JOURNAL OF CELL BIOLOGY

Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease

(2015) Matthew R Halliday et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier

(2015) Steffen E. Storck et al.   JOURNAL OF CLINICAL INVESTIGATION

Formation and maintenance of the BBB

(2015) Marie Blanchette et al.   MECHANISMS OF DEVELOPMENT

The re-emergence of antigen-specific tolerance as a potential therapy for MS

(2015) Lawrence Steinman   Multiple Sclerosis Journal

Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study

(2015) Charles RG Guttmann et al.   Multiple Sclerosis Journal

Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance

(2015) Zhen Zhao et al.   NATURE NEUROSCIENCE

Re-evaluation of the Blood-Brain Barrier in the Presence of Alzheimer’s Disease Pathology

(2015) Jason D. Ulrich et al.   NEURON

Lack of Widespread BBB Disruption in Alzheimer’s Disease Models: Focus on Therapeutic Antibodies

(2015) Nga Bien-Ly et al.   NEURON

Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

(2015) Axel Montagne et al.   NEURON

The re-emergence of antigen-specific tolerance as a potential therapy for MS

(2015) Lawrence Steinman   Multiple Sclerosis Journal

Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study

(2015) Charles RG Guttmann et al.   Multiple Sclerosis Journal

New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains

(2015) Seiji Miyata   Frontiers in Neuroscience

Efflux transporters in blood-brain interfaces of the developing brain

(2015) Nathalie Strazielle et al.   Frontiers in Neuroscience

Diurnal Variation in P-glycoprotein-Mediated Transport and Cerebrospinal Fluid Turnover in the Brain

(2014) Laura Kervezee et al.   AAPS Journal

PECAM-1: regulator of endothelial junctional integrity

(2014) Jamie R. Privratsky et al.   CELL AND TISSUE RESEARCH

Gpr124 Controls CNS Angiogenesis and Blood-Brain Barrier Integrity by Promoting Ligand-Specific Canonical Wnt Signaling

(2014) Yulian Zhou et al.   DEVELOPMENTAL CELL

Human Apolipoprotein E ε4 Expression Impairs Cerebral Vascularization and Blood—Brain Barrier Function in Mice

(2014) Wael Alata et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Canonical WNT signaling components in vascular development and barrier formation

(2014) Yulian Zhou et al.   JOURNAL OF CLINICAL INVESTIGATION

Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility

(2014) Lillian Cruz-Orengo et al.   JOURNAL OF CLINICAL INVESTIGATION

Rapid Remodeling of Tight Junctions during Paracellular Diapedesis in a Human Model of the Blood–Brain Barrier

(2014) Ryan C. Winger et al.   JOURNAL OF IMMUNOLOGY

Mfsd2a is critical for the formation and function of the blood–brain barrier

(2014) Ayal Ben-Zvi et al.   NATURE

Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid

(2014) Long N. Nguyen et al.   NATURE

Stepwise Recruitment of Transcellular and Paracellular Pathways Underlies Blood-Brain Barrier Breakdown in Stroke

(2014) Daniel Knowland et al.   NEURON

Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes

(2014) Yue Wang et al.   PLoS One

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

(2013) Michelle A Erickson et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain

(2013) Fanny Langlet et al.   JOURNAL OF COMPARATIVE NEUROLOGY

Development, maintenance and disruption of the blood-brain barrier

(2013) Birgit Obermeier et al.   NATURE MEDICINE

Developing Therapeutic Antibodies for Neurodegenerative Disease

(2013) Y. Joy Yu et al.   Neurotherapeutics

Tight junction-related human diseases

(2013) Norimasa Sawada   PATHOLOGY INTERNATIONAL

Sleep Drives Metabolite Clearance from the Adult Brain

(2013) L. Xie et al.   SCIENCE

Norrin/Frizzled4 Signaling in Retinal Vascular Development and Blood Brain Barrier Plasticity

(2012) Yanshu Wang et al.   CELL

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease

(2012) Azeb Tadesse Argaw et al.   JOURNAL OF CLINICAL INVESTIGATION

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

(2012) Marco Reis et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

(2012) Robert D. Bell et al.   NATURE

Laminin-411 Is a Vascular Ligand for MCAM and Facilitates TH17 Cell Entry into the CNS

(2012) Ken Flanagan et al.   PLoS One

A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid  

(2012) J. J. Iliff et al.   Science Translational Medicine

Capture, crawl, cross: the T cell code to breach the blood–brain barriers

(2012) Britta Engelhardt et al.   TRENDS IN IMMUNOLOGY

Evolution of the blood-brain barrier in newly forming multiple sclerosis lesions

(2011) María I. Gaitán et al.   ANNALS OF NEUROLOGY

Role of ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions

(2011) Igal Ifergan et al.   ANNALS OF NEUROLOGY

Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises

(2011) Annika Armulik et al.   DEVELOPMENTAL CELL

Apolipoprotein E Regulates the Integrity of Tight Junctions in an Isoform-dependent Manner in anin VitroBlood-Brain Barrier Model

(2011) Kazuchika Nishitsuji et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Central nervous system pericytes in health and disease

(2011) Ethan A Winkler et al.   NATURE NEUROSCIENCE

Heterogeneity of CNS myeloid cells and their roles in neurodegeneration

(2011) Marco Prinz et al.   NATURE NEUROSCIENCE

Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet

(2011) N. N. Haj-Yasein et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ABC Transporters and Drug Efflux at the Blood-Brain Barrier

(2011) Shanshan Shen et al.   REVIEWS IN THE NEUROSCIENCES

Disruption of central nervous system barriers in multiple sclerosis

(2010) Jorge Ivan Alvarez et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Postictal blood–brain barrier breakdown on contrast-enhanced MRI

(2010) Vincent Alvarez et al.   EPILEPSY & BEHAVIOR

Tumor Necrosis Factor-α Mediates the Blood–Brain Barrier Dysfunction Induced by Activated Microglia in Mouse Brain Microvascular Endothelial Cells

(2010) Tsuyoshi Nishioku et al.   JOURNAL OF PHARMACOLOGICAL SCIENCES

Pericytes regulate the blood–brain barrier

(2010) Annika Armulik et al.   NATURE

Pericytes are required for blood–brain barrier integrity during embryogenesis

(2010) Richard Daneman et al.   NATURE

Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

(2010) Marta Cortes-Canteli et al.   NEURON

Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS

(2010) Takeshi Nishijima et al.   NEURON

Pericytes Control Key Neurovascular Functions and Neuronal Phenotype in the Adult Brain and during Brain Aging

(2010) Robert D. Bell et al.   NEURON

The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial Cells

(2010) Richard Daneman et al.   PLoS One

Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease

(2009) Robert D. Bell et al.   ACTA NEUROPATHOLOGICA

Norrin, Frizzled-4, and Lrp5 Signaling in Endothelial Cells Controls a Genetic Program for Retinal Vascularization

(2009) Xin Ye et al.   CELL

Involvement of ROS in BBB dysfunction

(2009) Pamela B. L. Pun et al.   FREE RADICAL RESEARCH

Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions

(2009) Ingo Bartholomäus et al.   NATURE

C-C chemokine receptor 6–regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE

(2009) Andrea Reboldi et al.   NATURE IMMUNOLOGY

Endothelial basement membrane laminin α5 selectively inhibits T lymphocyte extravasation into the brain

(2009) Chuan Wu et al.   NATURE MEDICINE

Wnt/ -catenin signaling is required for CNS, but not non-CNS, angiogenesis

(2009) R. Daneman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown

(2009) Azeb Tadesse Argaw et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Blood–brain barrier permeability in Alzheimer's disease: a case–control MRI study

(2009) John M. Starr et al.   PSYCHIATRY RESEARCH-NEUROIMAGING

Molecular Basis of the Core Structure of Tight Junctions

(2009) M. Furuse   Cold Spring Harbor Perspectives in Biology

Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor

(2008) Matthew T. Andrews et al.   AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY

Evidence for Altered LRP/RAGE Expression in Alzheimer Lesion Pathogenesis

(2008) Brian Jeynes et al.   Current Alzheimer Research

Wnt/β-catenin signaling controls development of the blood–brain barrier

(2008) Stefan Liebner et al.   JOURNAL OF CELL BIOLOGY

A leaky blood-brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer’s disease brain

(2008) Jae K. Ryu et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

A role for leukocyte-endothelial adhesion mechanisms in epilepsy

(2008) Paolo F Fabene et al.   NATURE MEDICINE

The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders

(2008) Berislav V. Zlokovic   NEURON

Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature

(2008) J. M. Stenman et al.   SCIENCE

Barriers in the brain: a renaissance?

(2008) Norman R. Saunders et al.   TRENDS IN NEUROSCIENCES

Blood–brain barrier: Ageing and microvascular disease – systematic review and meta-analysis

(2007) Andrew J. Farrall et al.   NEUROBIOLOGY OF AGING