53,136 results match your criteria blood-brain barrier


In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells.

Eur J Pharm Biopharm 2021 Apr 7. Epub 2021 Apr 7.

INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal.

The BBB is a protective entity that prevents external substances from reaching the CNS but it also hinders the delivery of drugs into the brain when they are needed. The main objective of this work was to improve a previously proposed in vitro cell-based model by using a more physiological cell line (hCMEC/D3) to predict the main pharmacokinetic parameters that describe the access and distribution of drugs in the CNS: Kp, f, f and V. The hCMEC/D3 permeability of seven drugs was studied in transwell systems under different conditions (standard, modified with albumin and modified with brain homogenate). Read More

View Article and Full-Text PDF

Down-regulation of Astrocytic Sonic Hedgehog by Activation of Endothelin ET Receptors: Involvement in Traumatic Brain Injury-induced Disruption of Blood Brain Barrier in a Mouse Model.

Neurochem Int 2021 Apr 7:105042. Epub 2021 Apr 7.

Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita, Higashinada, Kobe, 668-8558, Japan. Electronic address:

In the adult brain, sonic hedgehog acts on cerebral microvascular endothelial cells to stabilize the blood-brain barrier. The expression of sonic hedgehog by astrocytes is altered during brain injury, and this change has been shown to affect permeability of blood-brain barrier. However, much remains unknown about the regulation of astrocytic sonic hedgehog production. Read More

View Article and Full-Text PDF

Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage.

Sci Rep 2021 Apr 9;11(1):7818. Epub 2021 Apr 9.

Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Subarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are characterized by blood-brain barrier (BBB) impairment. Read More

View Article and Full-Text PDF

Longitudinal imaging of T-cells and inflammatory demyelination in a preclinical model of multiple sclerosis using F-FAraG PET and MRI.

J Nucl Med 2021 Apr 9. Epub 2021 Apr 9.

University of California San Francisco, United States.

Lymphocytes and innate immune cells are key drivers of multiple sclerosis (MS) and are the main target of MS disease modifying therapies (DMT). Ex vivo analyses of MS lesions have revealed cellular heterogeneity and variable T-cell levels, which may have important implication for patient stratification and choice of DMT. Although magnetic resonance imaging (MRI) has proven valuable to monitor DMT efficacy, its lack of specificity for cellular subtypes highlights the need for complementary methods to improve lesion characterization. Read More

View Article and Full-Text PDF

A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease.

Alzheimers Res Ther 2021 Apr 9;13(1):76. Epub 2021 Apr 9.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.

Background: Aducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer's disease (AD) trials; however, it is controversial whether it also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), which temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. Read More

View Article and Full-Text PDF

CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts with infection.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;

CD47 is an antiphagocytic "don't eat me" signal that inhibits programmed cell removal of self. As red blood cells (RBCs) age they lose CD47 expression and become susceptible to programmed cell removal by macrophages. CD47 mice infected with , which exhibits an age-based preference for young RBCs, were previously demonstrated to be highly resistant to malaria infection. Read More

View Article and Full-Text PDF

GLOS and HARM in patients with transient neurovascular symptoms with and without ischemic infarction.

J Neuroradiol 2021 Apr 6. Epub 2021 Apr 6.

Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.

Background And Purpose: Gadolinium leakage in ocular structures (GLOS) on fluid attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke and other neurological disorders.

Methods: In patients with transient neurovascular symptoms who underwent repeated MRI with intravenous contrast agent administration, the presence of acute ischemic lesions on diffusion-weighted images (DWI) as well as the frequency and pattern of blood-brain barrier and blood-retina barrier impairment as demonstrated by the hyperintense acute reperfusion marker (HARM) and GLOS respectively on postcontrast FLAIR were evaluated.

Results: Overall 28 patients with transient neurovascular symptoms (median age 70. Read More

View Article and Full-Text PDF

Letter to the Editor: Brain renin-angiotensin system and liver-directed siRNA targeted to angiotensinogen.

Clin Sci (Lond) 2021 Apr;135(7):907-910

Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC 27157, U.S.A.

View Article and Full-Text PDF

Effects of intranasal guanosine administration on brain function in a rat model of ischemic stroke.

Purinergic Signal 2021 Apr 9. Epub 2021 Apr 9.

Graduate Program in Biological Science: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Ischemic stroke is a major cause of morbidity and mortality worldwide and only few affected patients are able to receive treatment, especially in developing countries. Detailed pathophysiology of brain ischemia has been extensively studied in order to discover new treatments with a broad therapeutic window and that are accessible to patients worldwide. The nucleoside guanosine (Guo) has been shown to have neuroprotective effects in animal models of brain diseases, including ischemic stroke. Read More

View Article and Full-Text PDF

Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins' Mimicry of Human Protein Interactions.

Front Hum Neurosci 2021 23;15:656313. Epub 2021 Mar 23.

Research Center for Translational Medicine, Koç University, Istanbul, Turkey.

The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins. Available 11 of the 29 SARS-CoV-2 proteins' structures have been extracted from Protein Data Bank. Read More

View Article and Full-Text PDF

Rectosigmoid ischemia and cerebral coma following gadolinium-induced anaphylaxis: A new manifestation of Kounis syndrome presented as devastating complication.

Ann Ital Chir 2020 ;91:442-444

Gadolinium-based contrast mediums are the most commonly used agents in magnetic resonance imaging for both angiography, and brain tumor enhancement due to their association with the degradation of the blood-brain barrier. When oxidation is removed from gadolinium medium and gadolinium salts, a silvery-white metal anions remain that are able to induce allergic reactions and anaphylaxis. Whereas such reactions are not common, other reactions including nephrogenic systemic fibrosis and acute kidney injury due to primary excretion of gadolinium from the kidneys and various cardiac arrhythmias including QTc electrocardiographic prolongation are occasionally encountered 1,2. Read More

View Article and Full-Text PDF
January 2020

Novel potent bifunctional carboxylesterase inhibitors based on a polyfluoroalkyl-2-imino-1,3-dione scaffold.

Eur J Med Chem 2021 Mar 15;218:113385. Epub 2021 Mar 15.

Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

An expanded series of alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates (HOPs) 3 was obtained via Cu(OAc)-catalyzed azo coupling. All were nanomolar inhibitors of carboxylesterase (CES), while moderate or weak inhibitors of acetylcholinesterase and butyrylcholinesterase. Steady-state kinetics studies showed that HOPs 3 are mixed type inhibitors of the three esterases. Read More

View Article and Full-Text PDF

TLR4-pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury.

Br J Pharmacol 2021 Apr 8. Epub 2021 Apr 8.

InstitutoTeófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.

Background And Purpose: Activation of astrocytes contributes to synaptic remodelling, tissue repair and neuronal survival following traumatic brain injury (TBI). However, the mechanisms by which these cells interact to resident/infiltrated inflammatory cells to rewire neuronal networks and repair brain functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI. Read More

View Article and Full-Text PDF

An In Vitro Assay to Monitor Sertoli Cell Blood-Testis Barrier (BTB) Integrity.

Methods Mol Biol 2021 Apr 9. Epub 2021 Apr 9.

The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

In this chapter, we detail a reliable, effective, and easy to perform assay to monitor the Sertoli cell blood-testis barrier (BTB) integrity. While the BTB in the testis is composed of the tight junction (TJ) barrier and basal ES (ectoplasmic specialization, a testis-specific actin-rich adherens junction (AJ) type), this method is applicable to all other blood-tissue barrier in vitro, including endothelial TJ-barrier of the blood-brain barrier (BBB). Furthermore, this method does not require expensive set up, and can be rapidly performed by any standard biochemistry/cell biology/molecular biology laboratory. Read More

View Article and Full-Text PDF

Design and synthesis of novel tacrine-indole hybrids as potential multitarget-directed ligands for the treatment of Alzheimer's disease.

Future Med Chem 2021 Apr 8. Epub 2021 Apr 8.

Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove 500 05, Czech Republic.

The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine and indole moieties. Tacrine-indole heterodimers were designed to inhibit cholinesterases and β-amyloid formation, and to cross the blood-brain barrier. The most potent new acetylcholinesterase inhibitors were compounds and (IC = 25 and 39 nM, respectively). Read More

View Article and Full-Text PDF

Clarithromycin Ameliorates Early Brain Injury After Subarachnoid Hemorrhage via Suppressing Periostin-Related Pathways in Mice.

Neurotherapeutics 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Subarachnoid hemorrhage (SAH) remains a life-threatening disease, and early brain injury (EBI) is an important cause of poor outcomes. The authors have reported that periostin, a matricellular protein, is one of key factors of post-SAH EBI. Clarithromycin (CAM) is a worldwide antibiotic that can inhibit periostin expression. Read More

View Article and Full-Text PDF

Meningeal blood-brain barrier disruption in acute traumatic brain injury.

Brain Commun 2020 9;2(2):fcaa143. Epub 2020 Sep 9.

Acute Cerebrovascular Diagnostics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

The meninges serve as a functional barrier surrounding the brain, critical to the immune response, and can be compromised following head trauma. Meningeal enhancement can be detected on contrast-enhanced MRI in patients presenting with acute traumatic brain injury, even when head CT is negative. Following head trauma, gadolinium-based contrast appears to extravasate from the vasculature, enhancing the dura within minutes, and later permeates the subarachnoid space. Read More

View Article and Full-Text PDF
September 2020

Neuronal Mechanisms Underlying Opioid Induced Respiratory Depression: Our Current Understanding.

J Neurophysiol 2021 Apr 7. Epub 2021 Apr 7.

University of Florida.

Opioid induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within the U.S. Read More

View Article and Full-Text PDF

Inhibition of GPR4 attenuates SH-SY5Y cell injury in cerebral ischemia/reperfusion via anti-apoptotic pathways.

Acta Biochim Pol 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurology, The First Hospital of Zibo, Zibo City, Shandong Province, 255200, China.

Cerebral ischemia/reperfusion injury (CIRI) can lead to increased vascular endothelial permeability and blood-brain barrier damage in patients with stroke. G protein-coupled receptor 4 (GPR4) is a functional pH sensor that plays a key role in renal ischemia-reperfusion-induced apoptosis. However, whether GPR4 has a role in cerebral ischemia remains to be further studied. Read More

View Article and Full-Text PDF

Efficient antiglioblastoma therapy in mice through doxorubicin-loaded nanomicelles modified using a novel brain-targeted RVG-15 peptide.

J Drug Target 2021 Apr 7:1-37. Epub 2021 Apr 7.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Glioblastoma is an aggressive malignancy and therapeutic options are limited due to the presence of the blood-brain barrier (BBB). RVG-29, a 29-amino-acid polypeptide derived from the rabies virus glycoprotein, has good drug-carrying capacity across the BBB. We reduced the size of this peptide to 15 amino acids (RVG-15), while retaining its capacity to cross the BBB. Read More

View Article and Full-Text PDF

Experimental Dopamine Reuptake Inhibitors in Parkinson's Disease: A Review of the Evidence.

Authors:
Thomas Müller

J Exp Pharmacol 2021 29;13:397-408. Epub 2021 Mar 29.

Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, 13088, Germany.

Parkinson's disease (PD) is the second most chronic neurodegenerative disorder worldwide. Deficit of monoamines, particularly dopamine, causes an individually varying compilation of motor and non-motor features. Constraint of presynaptic uptake extends monoamine stay in the synaptic cleft. Read More

View Article and Full-Text PDF

Epigenetics in blood-brain barrier disruption.

Fluids Barriers CNS 2021 Apr 6;18(1):17. Epub 2021 Apr 6.

The Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center, 6431 Fannin St. MSB 7.147, Houston, TX, 77030, USA.

The vessels of the central nervous system (CNS) have unique barrier properties. The endothelial cells (ECs) which comprise the CNS vessels contribute to the barrier via strong tight junctions, specific transporters, and limited endocytosis which combine to protect the brain from toxins and maintains brain homeostasis. Blood-brain barrier (BBB) leakage is a serious secondary injury in various CNS disorders like stroke, brain tumors, and neurodegenerative disorders. Read More

View Article and Full-Text PDF

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection.

Inflammopharmacology 2021 Apr 6. Epub 2021 Apr 6.

Technical University of Sofia, Klement Ohridksi 8, 1000, Sofia, Bulgaria.

Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in December 2019. SARS-CoV-2 has infected several millions of people, resulting in a huge socioeconomic cost and over 2.5 million deaths worldwide. Read More

View Article and Full-Text PDF

Leptin, the brain and energy homeostasis: From an apparently simple to a highly complex neuronal system.

Rev Endocr Metab Disord 2021 Apr 6. Epub 2021 Apr 6.

Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Tronto 10/A, 60020, Ancona, Italy.

Leptin, produced and secreted by white adipose tissue in tight relationship with adipose mass, informs the brain about the status of the energy stores serving as the main peripheral signal for energy balance regulation through interaction with a multitude of highly interconnected neuronal populations. Most obese patients display resistance to the anorectic effect of the hormone. The present review unravels the multiple levels of complexity that trigger hypothalamic response to leptin with the objective of highlighting those critical hubs that, mainly in the hypothalamic arcuate nucleus, may undergo obesity-induced alterations and create an obstacle to leptin action. Read More

View Article and Full-Text PDF

Analysis of Circulating Exosomes Reveals a Peripheral Signature of Astrocytic Pathology in Schizophrenia.

World J Biol Psychiatry 2021 Apr 6:1-31. Epub 2021 Apr 6.

St. Joseph's Hospital and Medical Center, Norton Thoracic Institute.

Objectives: Extracellular vesicles, including exosomes, cross the blood brain barrier with their contents intact and can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in schizophrenia. This study aimed to examine neuropathology-relevant protein biomarkers in circulating plasma-derived exosomes from patients with schizophrenia and age- and sex-matched healthy controls. Read More

View Article and Full-Text PDF

Choroid plexus and CSF: an updated review.

Br J Neurosurg 2021 Apr 6:1-9. Epub 2021 Apr 6.

Department of Neurosurgery, Ninewells Hospital, Dundee, UK.

In this article, we review the available literature about the functions of the choroid plexus (ChP), including its basic role in cerebrospinal fluid (CSF) secretion, renewal and absorption. We discuss more recently described, lesser-known functions of the ChP, such as its role in circadian rhythm regulation, chemical and immune surveillance and functional implications of ChP disruption, as occurs in neurodegenerative disorders. Read More

View Article and Full-Text PDF

Numerical approach-based simulation to predict cerebrovascular shear stress in a blood-brain barrier organ-on-a-chip.

Biosens Bioelectron 2021 Mar 26;183:113197. Epub 2021 Mar 26.

Department of Mechanical Engineering, Dong-A University, Busan, 49315, Republic of Korea. Electronic address:

Most of the compounds are impermeable to the blood-brain barrier (BBB), which poses a significant challenge in the development of therapeutics for the treatment of neurological diseases. Most of the existing in vitro BBB models are not capable of mimicking the in vivo conditions and functions. The numerical approach-based simulation model was proposed to accurately predict the in vivo level shear stress for the microfluidic BBB-on-a-chip. Read More

View Article and Full-Text PDF

Neurovascular multiparametric MRI defines epileptogenic and seizure propagation regions in experimental mesiotemporal lobe epilepsy.

Epilepsia 2021 Apr 5. Epub 2021 Apr 5.

Univ. Grenoble Alpes, Grenoble Institut Neurosciences, Inserm, U1216, Grenoble 38000, France.

Objective: Improving the identification of the epileptogenic zone and associated seizure-spreading regions represents a significant challenge. Innovative brain-imaging modalities tracking neurovascular dynamics during seizures may provide new disease biomarkers.

Methods: With use of a multi-parametric magnetic resonance imaging (MRI) analysis at 9. Read More

View Article and Full-Text PDF

Neuroimmune connections between corticotropin-releasing hormone and mast cells: novel strategies for the treatment of neurodegenerative diseases.

Neural Regen Res 2021 Nov;16(11):2184-2197

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Corticotropin-releasing hormone is a critical component of the hypothalamic-pituitary-adrenal axis, which plays a major role in the body's immune response to stress. Mast cells are both sensors and effectors in the interaction between the nervous and immune systems. As first responders to stress, mast cells can initiate, amplify and prolong neuroimmune responses upon activation. Read More

View Article and Full-Text PDF
November 2021

Toward three-dimensional models to study neurovascular unit functions in health and disease.

Neural Regen Res 2021 Nov;16(11):2132-2140

Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland.

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen. This supply is coordinated by the action of neurons, glial and vascular cells, known collectively as the neurovascular unit, which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling. In many neurodegenerative diseases, changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier, cerebral blood flow and clearance of waste from the brain. Read More

View Article and Full-Text PDF
November 2021