4,243 results match your criteria bbb dysfunction


Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases.

Front Cell Neurosci 2021 26;15:627682. Epub 2021 Mar 26.

Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United States.

Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. Read More

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A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood-Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.

Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. Read More

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Icaritin Provides Neuroprotection in Parkinson's Disease by Attenuating Neuroinflammation, Oxidative Stress, and Energy Deficiency.

Antioxidants (Basel) 2021 Mar 29;10(4). Epub 2021 Mar 29.

National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.

Neuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson's disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress using various approaches has not led to meaningful clinical outcomes, and mitochondrial enhancers have also failed to convincingly achieve disease-modifying effects. We tested our hypothesis that treatment approaches in PD should simultaneously reduce neuroinflammation, oxidative stress, and improve alterations in neuronal energy metabolism using the flavonoid icaritin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Read More

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Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain.

Glioblastoma (GBM) is the most common of all brain malignant tumors; it displays a median survival of 14.6 months with current complete standard treatment. High heterogeneity, aggressive and invasive behavior, the impossibility of completing tumor resection, limitations for drug administration and therapeutic resistance to current treatments are the main problems presented by this pathology. Read More

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Interactions of SARS-CoV-2 with the Blood-Brain Barrier.

Int J Mol Sci 2021 Mar 6;22(5). Epub 2021 Mar 6.

Geriatric Research Education and Clinical Center, VA Puget Sound Healthcare System, Seattle, WA 98108, USA.

Emerging data indicate that neurological complications occur as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The blood-brain barrier (BBB) is a critical interface that regulates entry of circulating molecules into the CNS, and is regulated by signals that arise from the brain and blood compartments. In this review, we discuss mechanisms by which SARS-CoV-2 interactions with the BBB may contribute to neurological dysfunction associated with coronavirus disease of 2019 (COVID-19), which is caused by SARS-CoV-2. Read More

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CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo.

Toxins (Basel) 2021 Mar 8;13(3). Epub 2021 Mar 8.

Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy.

Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tumoral mass, increasing survival of glioma-bearing mice and protecting peritumoral neural tissue from dysfunction. Read More

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Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study.

Int J Environ Res Public Health 2021 Mar 7;18(5). Epub 2021 Mar 7.

Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy.

In recent years, alcohol abuse has dramatically grown with deleterious consequence for people's health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood-brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. Read More

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Quantitative Proteomics-Based Blood-Brain Barrier Study.

Authors:
Yasuo Uchida

Biol Pharm Bull 2021 ;44(4):465-473

Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University.

From the viewpoint of drug discovery, it is an important issue to elucidate the drug permeability at the human central nervous system (CNS) barriers and the molecular mechanisms in the cells forming CNS barriers especially during CNS diseases. I introduced quantitative proteomics techniques into the blood-brain barrier (BBB) study, then quantitatively investigated the transport system at the human BBB and clarified the quantitative differences in protein expression levels and functions of transporters and receptors between animals and humans, or in vitro and in vivo. Based on the difference in the absolute expression level of transporters between in vitro and in vivo, I demonstrated that the drug efflux activity of P-glycoprotein (P-gp) at in vivo BBB can be accurately reconstructed from the in vitro system, not only in mouse models but also monkeys similar to humans and pathological conditions. Read More

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January 2021

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis.

Mol Neurobiol 2021 Mar 27. Epub 2021 Mar 27.

Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky, 40202, USA.

Traumatic brain injury (TBI) is a damage to the brain from an external force that results in temporary or permanent impairment in brain functions. Unfortunately, not many treatment options are available to TBI patients. Therefore, knowledge of the complex interplay between gut microbiome (GM) and brain health may shed novel insights as it is a rapidly expanding field of research around the world. Read More

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In vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood--Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.

Curr Alzheimer Res 2021 Mar 24. Epub 2021 Mar 24.

Faculty of Physical Chemistry, University of Belgrade, Belgrade. Serbia.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. Read More

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Sex differences in the blood-brain barrier and neurodegenerative diseases.

APL Bioeng 2021 Mar 16;5(1):011509. Epub 2021 Mar 16.

Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA.

The number of people diagnosed with neurodegenerative diseases is on the rise. Many of these diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and motor neuron disease, demonstrate clear sexual dimorphisms. While sex as a biological variable must now be included in animal studies, sex is rarely included in models of human neurodegenerative disease. Read More

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Mdivi-1 alleviates brain damage and synaptic dysfunction after intracerebral hemorrhage in mice.

Exp Brain Res 2021 Mar 22. Epub 2021 Mar 22.

School of Forensic Medicine, Wannan Medical College, Wuhu, 241002, Anhui, China.

As a selective inhibitor of mitochondrial fission protein dynamin-related protein-1 (Drp1), mitochondrial division inhibitor 1 (mdivi-1) can cross the blood-brain barrier (BBB) and exert neuroprotection. However, it remains unclear whether mdivi-1 can attenuate intracerebral hemorrhage (ICH)-induced secondary brain injury. This study was undertaken to characterize the roles of mdivi-1 in short-term and long-term behavioral outcomes, along with synaptic plasticity changes in mice after ICH. Read More

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Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro.

Fluids Barriers CNS 2021 Mar 18;18(1):13. Epub 2021 Mar 18.

Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich, Switzerland.

Background: Astrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment. Read More

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Resolvin D1 ameliorates Inflammation-Mediated Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in rats by Modulating A20 and NLRP3 Inflammasome.

Front Pharmacol 2020 3;11:610734. Epub 2021 Feb 3.

Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Inflammation is typically related to dysfunction of the blood-brain barrier (BBB) that leads to early brain injury (EBI) after subarachnoid hemorrhage (SAH). Resolvin D1 (RVD1), a lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and neuroprotective properties. This study investigated the effects and mechanisms of RVD1 in SAH. Read More

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February 2021

Evaluating the endothelial-microglial interaction and comprehensive inflammatory marker profiles under acute exposure to ultrafine diesel exhaust particles in vitro.

Toxicology 2021 Apr 13;454:152748. Epub 2021 Mar 13.

Department of Environmental Science, Baylor University, 101 Bagby Ave., Waco, TX, 76706, USA. Electronic address:

Exposure to combustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because people in urban areas are continuously exposed, and once inhaled, fine and ultrafine DEP may reach the brain. The blood-brain barrier (BBB) endothelial cells (EC) and the perivascular microglia protect the brain from circulating pathogens and neurotoxic molecules like DEP. While the BBB-microglial interaction is critical for maintaining homeostasis, no study has previously evaluated the endothelial-microglial interaction nor comprehensively characterized these cells' inflammatory marker profiles under ultrafine DEP exposures in vitro. Read More

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Resveratrol Attenuates Meningitic -Mediated Blood-Brain Barrier Disruption.

ACS Infect Dis 2021 Apr 16;7(4):777-789. Epub 2021 Mar 16.

State Key Laboratory of Agricultural Microbiology, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Meningitic can infiltrate the central nervous system (CNS), consequently increasing the levels of proinflammatory cytokines and chemokines and deteriorating the integrity of the blood-brain barrier (BBB). Resveratrol has emerged in recent years as a compound with antioxidant and anti-inflammatory properties. However, it is still unknown how resveratrol affects meningitic -induced CNS dysfunction. Read More

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Alzheimer's disease pathology is associated with earlier alterations to blood-brain barrier water permeability compared with healthy ageing in TgF344-AD rats.

NMR Biomed 2021 Mar 15:e4510. Epub 2021 Mar 15.

Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine, and Health, Stopford Building, University of Manchester, Manchester, UK.

The effects of Alzheimer's disease (AD) and ageing on blood-brain barrier (BBB) breakdown are investigated in TgF344-AD and wild-type rats aged 13, 18 and 21 months. Permeability surface area products of the BBB to water (PS ) and gadolinium-based contrast agent (PS ) were measured in grey matter using multiflip angle multiecho dynamic contrast-enhanced MRI. At 13 months of age, there was no significant difference in PS between TgF344-AD and wild-types (p = 0. Read More

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Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer's disease.

Brain 2021 Mar 16. Epub 2021 Mar 16.

Dementia Research Group, Bristol Medical School, University of Bristol, Bristol, UK.

We studied the effects of systemic infection on brain cytokine level and cerebral vascular function in Alzheimer's disease (AD) and vascular dementia (VaD), in superior temporal cortex (BA22) from AD (n = 75), VaD (n = 22) and age-matched controls (n = 46), stratified according to the presence or absence of terminal systemic infection. Brain cytokine levels were measured using Mesoscale Discovery Multiplex Assays and markers of cerebrovascular function were assessed by ELISA. Multiple brain cytokines were elevated in AD and VaD: Interleukin (IL)-15 and IL-17A were maximally elevated in end-stage Alzheimer's disease (Braak tangle stage V-VI) whereas IL-2, IL-5, IL12p40 and IL-16 were highest in intermediate Braak tangle stage III-IV disease. Read More

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Inhibition of miR-103-3p Preserves Neurovascular Integrity Through Caveolin-1 in Experimental Subarachnoid Hemorrhage.

Neuroscience 2021 May 17;461:91-101. Epub 2021 Mar 17.

Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Caveolin-1 (Cav-1) is a constitutive structural protein of caveolae in the plasma membrane. It plays an important role in maintaining blood brain barrier (BBB) integrity. In this study, we identified that miR-103-3p, a hypoxia-responsive miRNA, could interact with Cav-1. Read More

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Neurovascular dysfunctions in hypertensive disorders of pregnancy.

Metab Brain Dis 2021 Mar 11. Epub 2021 Mar 11.

The Neuro- Lab, School of Health and Health Technology, Federal University of Technology, Akure, Nigeria.

Hypertensive disorders in pregnancy pose a huge challenge to the socioeconomic stability of a community; being a major cause of maternal and neonatal morbidity and mortality during delivery. Although there have been recent improvements in management strategies, still, the diversified nature of the underlying pathogenesis undermines their effectiveness. Generally, these disorders are categorized into two; hypertensive disorders of pregnancy with proteinuria (pre-eclampsia and eclampsia) and hypertensive disorders of pregnancy without proteinuria (gestational and chronic hypertension). Read More

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Behavioral comorbidities of epilepsy and neuroinflammation: Evidence from experimental and clinical studies.

Epilepsy Behav 2021 Apr 5;117:107869. Epub 2021 Mar 5.

Institute of Higher Nervous Activity and Neurophysiology of RAS, 117485 Butlerova 5A, Moscow, Russia. Electronic address:

Currently, a significant amount of data is accumulated showing that neuroinflammation is one of the key processes in the development of brain pathology in trauma, neurodegenerative diseases, and epilepsy. Various brain insults, such as prolonged seizure activity, trigger the activation of microglia and astrocytes in the brain. These cells, in turn, begin to synthesize pro-inflammatory cytokines. Read More

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Blood-brain Barrier Permeability Assays Using Epsilon Toxin.

Bio Protoc 2020 Aug 5;10(15):e3709. Epub 2020 Aug 5.

Brain and Mind Institute, Weill Cornell Medical College, New York City, New York, 10065, USA.

In order for the brain to function properly, a carefully orchestrated homeostasis must be maintained. To help regulate this delicate balance, the brain has developed a highly selective blood-brain barrier (BBB). Under normal conditions, the BBB excludes harmful blood-borne material from the brain parenchyma. Read More

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Blood-brain barrier dysfunction in ischemic stroke and diabetes: the underlying link, mechanisms and future possible therapeutic targets.

Anat Cell Biol 2021 Mar 4. Epub 2021 Mar 4.

Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Ischemic stroke caused by occlusion of cerebral artery is responsible for the majority of stroke that increases the morbidity and mortality worldwide. Diabetes mellitus (DM) is a crucial risk factor for ischemic stroke. Prolonged DM causes various microvascular and macrovascular changes, and blood-brain barrier (BBB) permeability that facilitates inflammatory response following stroke. Read More

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Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury.

Cells 2021 Feb 26;10(3). Epub 2021 Feb 26.

Spinal Cord and Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, KY 40536, USA.

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood-brain barrier (BBB) dysfunction and blood-brain cell interactions. Read More

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February 2021

Protective Effects of Aquaporin-4 Deficiency on Longer-term Neurological Outcomes in a Mouse Model.

Neurochem Res 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurosurgery, the Second Hospital of Hebei Medical University, No.215, Heping Road, Shijiazhuang, 050000, Hebei, China.

Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear. Read More

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Perillyl alcohol reduces parasite sequestration and cerebrovascular dysfunction during experimental cerebral malaria.

Antimicrob Agents Chemother 2021 Mar 1. Epub 2021 Mar 1.

Laboratory of Malaria Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.

Cerebral malaria (CM) is a severe immunovasculopathy which presents high mortality rate (15-20%), despite the availability of artemisinin-based therapy. More effective immunomodulatory and/or antiparasitic therapies are urgently needed. Experimental Cerebral Malaria (ECM) in mice is used to elucidate aspects involved in this pathology since manifests many of the neurological features of CM. Read More

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The psychoactive drug of abuse mephedrone differentially disrupts blood-brain barrier properties.

J Neuroinflammation 2021 Mar 1;18(1):63. Epub 2021 Mar 1.

Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, 3500 N Broad St, Philadelphia, PA, 19140, USA.

Background: Synthetic cathinones are a category of psychostimulants belonging to the growing number of designer drugs also known as "Novel Psychoactive Substances" (NPS). In recent years, NPS have gained popularity in the recreational drug market due to their amphetamine-like stimulant effects, low cost, ease of availability, and lack of detection by conventional toxicology screening. All these factors have led to an increase in NPS substance abuse among the young adults, followed by spike of overdose-related fatalities and adverse effects, severe neurotoxicity, and cerebral vascular complications. Read More

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Permeability of the Blood-Brain Barrier after Traumatic Brain Injury; Radiological Considerations.

J Neurotrauma 2021 Apr 12. Epub 2021 Apr 12.

Royal College of Surgeons in Ireland, Dublin, Ireland.

Traumatic brain injury (TBI) is a leading cause of death and disability, especially in young persons, and constitutes a major socioeconomic burden worldwide. It is regarded as the leading cause of mortality and morbidity in previously healthy young persons. Most of the mechanisms underpinning the development of secondary brain injury are consequences of disruption of the complex relationship between the cells and proteins constituting the neurovascular unit or a direct result of loss of integrity of the tight junctions (TJ) in the blood-brain barrier (BBB). Read More

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Neurovascular Units and Neural-Glia Networks in Intracerebral Hemorrhage: from Mechanisms to Translation.

Transl Stroke Res 2021 Feb 24. Epub 2021 Feb 24.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China.

Intracerebral hemorrhage (ICH), the most lethal type of stroke, often leads to poor outcomes in the clinic. Due to the complex mechanisms and cell-cell crosstalk during ICH, the neurovascular unit (NVU) was proposed to serve as a promising therapeutic target for ICH research. This review aims to summarize the development of pathophysiological shifts in the NVU and neural-glia networks after ICH. Read More

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February 2021

Serum Neurofilament Light in Patients with Frontotemporal Dementia Caused by CHMP2B Mutation.

Dement Geriatr Cogn Disord 2020 24;49(6):533-538. Epub 2021 Feb 24.

Neurogenetics Clinic & Research Lab, Danish Dementia Research Centre, Copenhagen, Denmark.

Introduction: The potential of neurofilament light (NfL) as a blood-based biomarker is currently being investigated in autosomal dominant neurodegenerative disease. This study explores the clinical utility of serum-NfL in frontotemporal dementia due to CHMP2B mutation (FTD-3).

Methods: This cross-sectional study included serum and CSF data from 38 members of the Danish FTD-3 family: 12 affected CHMP2B mutation carriers, 10 presymptomatic carriers, and 16 noncarriers. Read More

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February 2021