1,228 results match your criteria bbb structure

Three-dimensional remodeling of functional cerebrovascular architecture and gliovascular unit in leptin receptor-deficient mice.

J Cereb Blood Flow Metab 2021 Apr 4:271678X211006596. Epub 2021 Apr 4.

Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.

The cerebrovascular sequelae of diabetes render victims more susceptible to ischemic stroke, vascular cognitive impairment, and Alzheimer's disease. However, limited knowledge exists on the progressive changes in cerebrovascular structure and functional remodeling in type 2 diabetes. To ascertain the impact of diabetes on whole-brain cerebrovascular perfusion, leptin-receptor-deficient mice were transcardially injected with tomato-lectin before sacrifice. Read More

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Biomimetic Chromatographic Studies Combined with the Computational Approach to Investigate the Ability of Triterpenoid Saponins of Plant Origin to Cross the Blood-Brain Barrier.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, 20-031 Lublin, Poland.

Biomimetic (non-cell based in vitro) and computational (in silico) studies are commonly used as screening tests in laboratory practice in the first stages of an experiment on biologically active compounds (potential drugs) and constitute an important step in the research on the drug design process. The main aim of this study was to evaluate the ability of triterpenoid saponins of plant origin to cross the blood-brain barrier (BBB) using both computational methods, including QSAR methodology, and biomimetic chromatographic methods, i.e. Read More

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25-Hydroxycholesterol Effect on Membrane Structure and Mechanical Properties.

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

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as 25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses' entry into their target cells. 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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Development of blood brain barrier permeation prediction models for organic and inorganic biocidal active substances.

Chemosphere 2021 Mar 18;277:130330. Epub 2021 Mar 18.

Toxicoinformatics group, Department of predictive toxicology, Korea institute of toxicology, Daejeon 34114, Republic of Korea. Electronic address:

Biocidal products are broadly used in homes and industries. However, the safety of biocidal active substances (BASs) is not yet fully understood. In particular, the neurotoxic action of BASs needs to be studied as diverse epidemiological studies have reported associations between exposure to BASs and neural diseases. Read More

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Discovery of a series of 2-((1-phenyl-1H-imidazol-5-yl)methyl)-1H-indoles as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

ChemMedChem 2021 Mar 23. Epub 2021 Mar 23.

University Health Network, Krembil Research Institute, CANADA.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors for use in human cancers is now a focus of widespread research and development efforts. In this study, we report the structure-based design of 2-(5-imidazolyl)indole derivatives, a series of novel IDO1 inhibitors which have been designed and synthesized based on our previous study using N1-substituted 5-indoleimidazoles. Read More

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Developing novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems.

Eur J Med Chem 2021 Mar 2;216:113331. Epub 2021 Mar 2.

Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Via Licio Giorgieri 1, 34127, Trieste, Italy. Electronic address:

Protein kinase CK1δ expression and activity is involved in different pathological situations that include neuroinflammatory and neurodegenerative diseases. For this reason, protein kinase CK1δ has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems that resemble adenine of ATP represent optimal scaffolds for the development of a new class of ATP competitive CK1δ inhibitors. Read More

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Metformin derived carbon dots: Highly biocompatible fluorescent nanomaterials as mitochondrial targeting and blood-brain barrier penetrating biomarkers.

J Colloid Interface Sci 2021 Jun 19;592:485-497. Epub 2021 Feb 19.

Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, United States. Electronic address:

Carbon dots (CDs) have been intensively studied since their discovery in 2004 because of their unique properties such as low toxicity, excellent biocompatibility, high photoluminescence (PL) and good water dispersibility. In this study metformin derived carbon dots (Met-CDs) were synthesized using a microwave assisted method. Met-CDs were meticulously characterized using ultra-violet spectroscopy (UV-vis), photoluminescence (PL), Fourier Transform Infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), atomic force (AFM) and transmission electron (TEM) microscopies. Read More

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Protein Nanoparticle-Related Osmotic Pressure Modifies Nonselective Permeability of the Blood-Brain Barrier by Increasing Membrane Fluidity.

Int J Nanomedicine 2021 1;16:1663-1680. Epub 2021 Mar 1.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

Background: Intracellular tension plays a crucial role in the destruction of the blood-brain barrier (BBB) in response to lesion stimuli. Tight junction structure could be primarily affected by tension activity. In this study, we aimed to determine the effects of extracellular BBB damage on intracellular tension activity, and elucidate the mechanism underlying the effects of intracellular protein nanoparticle-related osmotic pressure on BBB permeability. Read More

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Cubosomes enhance drug permeability across the blood-brain barrier in zebrafish.

Int J Pharm 2021 Mar 3;600:120411. Epub 2021 Mar 3.

School of Pharmacy, University of Otago, PO Box 56, Dunedin 9054 Dunedin, New Zealand. Electronic address:

The potential of cubosomes to improve delivery of incorporated cargo to the brain was explored in zebrafish. Cubosomes were formulated with one of three stabilisers, Pluronic F68, Pluronic F127 or Tween 80, with the hypothesis that coating with Tween 80 will enable brain targeting of cubosomes as has been previously shown for polymeric nanoparticles. The physiochemical properties and the ability of the cubosomes to facilitate delivery of the model drug lissamine rhodamine (RhoB) into the brain was investigated. Read More

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Atorvastatin attenuates surgery-induced BBB disruption and cognitive impairment partly by suppressing NF-κB pathway and NLRP3 inflammasome activation in aged mice.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar 1. Epub 2021 Mar 1.

Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption are important contributors for cognitive impairment. Atorvastatin, as a strong HMG-CoA reductase inhibitor, has been widely used in clinic. Read More

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Decoding the Neuroprotective Potential of Methyl Gallate-Loaded Starch Nanoparticles against Beta Amyloid-Induced Oxidative Stress-Mediated Apoptosis: An In Vitro Study.

Pharmaceutics 2021 Feb 25;13(3). Epub 2021 Feb 25.

Department of Nanoscience and Technology, Alagappa University, Karaikudi 630003, India.

Alzheimer's disease (AD) is a multifaceted neuronal disorder and a challenge to medical practitioners, as the blood-brain barrier (BBB) acts as a major obstacle for drug delivery to the brain. Development of a nanomaterial-based drug delivery system (DDS) paved a way to penetrate the BBB. Starch, a ubiquitous natural biopolymer, has received much attention as a DDS due to its biocompatibility, biodegradability and eco-friendly nature. Read More

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February 2021

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

Acta Pharm Sin B 2021 Feb 25;11(2):373-393. Epub 2020 Aug 25.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Read More

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February 2021

Methods used for the measurement of blood-brain barrier integrity.

Metab Brain Dis 2021 Feb 26. Epub 2021 Feb 26.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

The blood-brain barrier (BBB) comprises the interface between blood, brain and cerebrospinal fluid. Its primary function, which is mainly carried out by tight junctions, is to stabilize the tightly controlled microenvironment of the brain. To study the development and maintenance of the BBB, as well as various roles their intrinsic mechanisms that play in neurological disorders, suitable measurements are required to demonstrate integrity and functional changes at the interfaces between the blood and brain tissue. Read More

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February 2021

Rational design of potent anti-COVID-19 main protease drugs: An extensive multi-spectrum in silico approach.

J Mol Liq 2021 May 12;330:115636. Epub 2021 Feb 12.

Foundation University Medical College, Foundation University Islamabad, Islambad, Pakistan.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a novel coronavirus and the etiological agent of global pandemic coronavirus disease (COVID-19) requires quick development of potential therapeutic strategies. Computer aided drug design approaches are highly efficient in identifying promising drug candidates among an available pool of biological active antivirals with safe pharmacokinetics. The main protease (M) enzyme of SARS-CoV-2 is considered key in virus production and its crystal structures are available at excellent resolution. Read More

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Targeting the HuR oncogenic role with a new class of cytoplasmic dimerization inhibitors.

Cancer Res 2021 Feb 18. Epub 2021 Feb 18.

Neuro-oncology Program, Department of Neurology, University of Alabama at Birmingham

The development of novel therapeutics that exploit alterations in the activation state of key cellular signaling pathways due to mutations in upstream regulators has generated the field of personalized medicine. These first-generation efforts have focused on actionable mutations identified by deep sequencing of large numbers of tumor samples. We propose that a second-generation opportunity exists by exploiting key downstream "nodes of control" that contribute to oncogenesis and are inappropriately activated due to loss of upstream regulation and microenvironmental influences. Read More

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February 2021

Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors.

Curr Alzheimer Res 2020 ;17(13):1177-1185

School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor, Malaysia.

Background: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.

Objective: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core. Read More

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January 2020

Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation.

Eur J Med Chem 2021 Apr 2;215:113224. Epub 2021 Feb 2.

Drug Design and Synthesis Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi, 110025, India. Electronic address:

Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. Read More

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Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.

Int J Mol Sci 2021 Jan 30;22(3). Epub 2021 Jan 30.

Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania.

Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Read More

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January 2021

Green Synthesis, Antioxidant, and Plant Growth Regulatory Activities of Novel α-Furfuryl-2-alkylaminophosphonates.

ACS Omega 2021 Feb 21;6(4):2934-2948. Epub 2021 Jan 21.

Department of Chemistry, Sri Venkateswara University, Tirupati 517502, Andhra Pradesh, India.

A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot three-component classical Kabachnik-Fields reaction in a green chemical approach by addition of an generated dialkylphosphite to Schiff's base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2-alkylaminophosphonates were screened to antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. Read More

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February 2021

Bioactive peptides in preventative healthcare: An overview of bioactivities and suggested methods to assess potential applications.

Maria Hayes

Curr Pharm Des 2021 Jan 25. Epub 2021 Jan 25.

Food BioSciences Department, Teagasc Food Research Centre, Ashtown, Dublin 15. Ireland.

Food derived bioactive peptides can be generated from various protein sources and usually consist of between 2-30 amino acids with bulky, side-chain aromatic amino acids preferred in the ultimate and penultimate positions at the Cterminal end of the amino acid chain. They are reported to impart a myriad of preventative health beneficial effects to the consumer once ingested and these include heart health benefits through inhibition of enzymes including renin (EC 3.4. Read More

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January 2021

Evolving new-age strategies to transport therapeutics across the blood-brain-barrier.

Int J Pharm 2021 Apr 2;599:120351. Epub 2021 Feb 2.

Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India; R&D Healthcare Division Emami Ltd., 13, BT Road, Belgharia, Kolkata 700056, India. Electronic address:

A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in targeting drugs specific to the brain. Neoplasm compromising the internal structure of BBB that results in impaired vasculature is called as blood tumor barrier (BTB). Besides, the BBB serves as a chief hindrance to the passage of a drug into the brain parenchyma. Read More

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Combined Toxicity of Metal Nanoparticles: Comparison of Individual and Mixture Particles Effect.

Ayse Basak Engin

Adv Exp Med Biol 2021 ;1275:165-193

Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.

Toxicity of metal nanoparticles (NPs) are closely associated with increasing intracellular reactive oxygen species (ROS) and the levels of pro-inflammatory mediators. However, NP interactions and surface complexation reactions alter the original toxicity of individual NPs. To date, toxicity studies on NPs have mostly been focused on individual NPs instead of the combination of several species. Read More

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February 2021

Blood-brain barrier integrity is the primary target of alcohol abuse.

Chem Biol Interact 2021 Mar 28;337:109400. Epub 2021 Jan 28.

Center for Phenomics of Traditional Chinese Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China. Electronic address:

The effects of long-term alcohol consumptions on cognitive function remain elusive with contradictory results. Whilst it is widely accepted that long-term intoxication can cause cognitive impairment, moderate drinking can improve cognitive function. In reality, many older people and those with chronic medical conditions are long-term alcohol consumers in Asian countries. Read More

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Artificial neural network approach for predicting blood brain barrier permeability based on a group contribution method.

Comput Methods Programs Biomed 2021 Mar 15;200:105943. Epub 2021 Jan 15.

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China; Engineering Research Center of Bio-Process, Ministry of Education, Hefei University of Technology, Hefei 230601, China. Electronic address:

Background And Objective: The purpose of this study was to develop a quantitative structure-activity relationship (QSAR) model for the prediction of blood brain barrier (BBB) permeability by using artificial neural networks (ANN) in combination with molecular structure and property descriptors.

Methods: Using a database composed of 300 compounds, 52 structure descriptors obtained based on the universal quasichemical functional group activity coefficients (UNIFAC) group contribution method and the selected 8 molecular property descriptors were used as the network inputs, whereas logBB values of compounds constituted its output.

Results: The correlation coefficient R of the constructed prediction model, the relative error (RE) and the root mean square error (RMSE) was 0. Read More

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Long-Term Near-Infrared Signal Tracking of the Therapeutic Changes of Glioblastoma Cells in Brain Tissue with Ultrasound-Guided Persistent Luminescent Nanocomposites.

ACS Appl Mater Interfaces 2021 Feb 28;13(5):6099-6108. Epub 2021 Jan 28.

Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.

The blood-brain barrier (BBB) is a physical barrier that selectively prevents certain substances from entering the brain through the blood. The BBB protects the brain from germs and causes difficulty in intracranial treatment. The chemotherapy drug temozolomide (TMZ), embedded in nanobubbles (NBs) and combined with persistent luminescent nanoparticles (PLNs), has been used to treat glioblastoma (GBM) effectively through image tracking. Read More

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February 2021

Occurrence of Morpholine in Central Nervous System Drug Discovery.

ACS Chem Neurosci 2021 02 18;12(3):378-390. Epub 2021 Jan 18.

Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy.

Developing drugs for the central nervous system (CNS) requires fine chemical modifications, as a strict balance between size and lipophilicity is necessary to improve the permeability through the blood-brain barrier (BBB). In this context, morpholine and its analogues represent valuable heterocycles, due to their conformational and physicochemical properties. In fact, the presence of a weak basic nitrogen atom and of an oxygen atom at the opposite position provides a peculiar p value and a flexible conformation to the ring, thus allowing it to take part in several lipophilic-hydrophilic interactions, and to improve blood solubility and brain permeability of the overall structure. Read More

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February 2021

Blood-Brain Barrier Disruption: A Common Driver of Central Nervous System Diseases.

Neuroscientist 2021 Jan 15:1073858420985838. Epub 2021 Jan 15.

Neurooncology Unit, Instituto de Salud Carlos III-UFIEC, Madrid, Spain.

The brain is endowed with a unique cellular composition and organization, embedded within a vascular network and isolated from the circulating blood by a specialized frontier, the so-called blood-brain barrier (BBB), which is necessary for its proper function. Recent reports have shown that increments in the permeability of the blood vessels facilitates the entry of toxic components and immune cells to the brain parenchyma and alters the phenotype of the supporting astrocytes. All of these might contribute to the progression of different pathologies such as brain cancers or neurodegenerative diseases. Read More

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January 2021

Bioconjugate Supramolecular Pd Metallacages Penetrate the Blood Brain Barrier and .

Bioconjug Chem 2021 Jan 13. Epub 2021 Jan 13.

Department of Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85748 Garching bei München, Germany.

The biomedical application of discrete supramolecular metal-based structures, specifically self-assembled metallacages, is still an emergent field of study. Capitalizing on the knowledge gained in recent years on the development of 3-dimensional (3D) metallacages as novel drug delivery systems and agents, we explore here the possibility to target [PdL] cages (L = 3,5-bis(3-ethynylpyridine)phenyl ligand) to the brain. In detail, a new water-soluble homoleptic cage () tethered to a blood brain barrier (BBB)-translocating peptide was synthesized by a combination of solid-phase peptide synthesis (SPPS) and self-assembly procedures. Read More

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January 2021

Astrocyte-Derived TGFβ1 Facilitates Blood-Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells.

Brain Sci 2021 Jan 8;11(1). Epub 2021 Jan 8.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

The blood-brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood-brain barrier (BBB) function. Here, we demonstrate the astrocyte-derived TGFβ1-mediated intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). Read More

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January 2021