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https://www.readbyqxmd.com/read/28890866/improving-brain-delivery-of-biomolecules-via-bbb-modulation-in-mouse-and-rat-detection-using-mri-nirf-and-mass-spectrometry
#1
Kavisha R Ulapane, Ngoc On, Paul Kiptoo, Todd D Williams, Donald W Miller, Teruna J Siahaan
There is an urgent need to develop new and alternative methods to deliver functional biomolecules to the brain for diagnosis and treatment of brain diseases. The goal of this study was to evaluate the activity of blood-brain barrier (BBB) modulators (i.e., HAV and ADT peptides) to deliver functional biomolecules (i.e., galbumin, IRdye800cw-cLABL, and cIBR7) to the brains of mice and rats. HAV6, cHAVc3, and ADTC5 peptides but not HAV4 peptide significantly enhanced the brain delivery of 65 kDa galbumin compared to control in Balb/c mice as quantified by magnetic resonance imaging (MRI)...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/28881830/value-of-quantitative-magnetic-resonance-imaging-t1-relaxometry-in-predicting-contrast-enhancement-in-glioblastoma-patients
#2
Elke Hattingen, Andreas Müller, Alina Jurcoane, Burkhard Mädler, Philip Ditter, Hans Schild, Ulrich Herrlinger, Martin Glas, Sied Kebir
SUMMARIZING THE IMPORTANCE OF THE STUDY: The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28860328/vascular-pathology-in-multiple-sclerosis-reframing-pathogenesis-around-the-blood-brain-barrier
#3
REVIEW
Jonathan I Spencer, Jack S Bell, Gabriele C DeLuca
Blood-brain barrier (BBB) disruption has long been recognised as an important early feature of multiple sclerosis (MS) pathology. Traditionally, this has been seen as a by-product of the myelin-specific immune response. Here, we consider whether vascular changes instead play a central role in disease pathogenesis, rather than representing a secondary effect of neuroinflammation or neurodegeneration. Importantly, this is not necessarily mutually exclusive from current hypotheses. Vascular pathology in a genetically predisposed individual, influenced by environmental factors such as pathogens, hypovitaminosis D and smoking, may be a critical initiator of a series of events including hypoxia, protein deposition and immune cell egress that allows the development of a CNS-specific immune response and the classical pathological and clinical hallmarks of disease...
August 31, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28841776/cholera-toxin-subunit-b-enabled-multifunctional-glioma-targeted-drug-delivery
#4
Juan Guan, Zui Zhang, Xuefeng Hu, Yang Yang, Zhilan Chai, Xiaoqin Liu, Jican Liu, Bo Gao, Weiyue Lu, Jun Qian, Changyou Zhan
Glioma is among the most formidable brain cancers due to location in the brain. Cholera toxin subunit B (CTB) is investigated to facilitate multifunctional glioma-targeted drug delivery by targeting the glycosphingolipid GM1 expressed in the blood-brain barrier (BBB), neovasulature, and glioma cells. When modified on the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CTB-NPs), CTB fully retains its bioactivity after 24 h incubation in the fresh mouse plasma. The formed protein corona (PC) of CTB-NP and plain PLGA nanoparticles (NP) after incubation in plasma is analyzed using liquid chromatography tandem massspectrometry (nano-LC-MS/MS)...
August 25, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28798954/acute-effect-of-pore-forming-clostridium-perfringens-%C3%AE%C2%B5-toxin-on-compound-action-potentials-of-optic-nerve-of-mouse
#5
Mercè Cases, Artur Llobet, Beatrice Terni, Inmaculada Gómez de Aranda, Marta Blanch, Briain Doohan, Alexander Revill, Angus M Brown, Juan Blasi, Carles Solsona
ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28797721/intact-blood-brain-barrier-transport-of-small-molecular-drugs-in-animal-models-of-amyloid-beta-and-alpha-synuclein-pathology
#6
Sofia Gustafsson, Veronica Lindström, Martin Ingelsson, Margareta Hammarlund-Udenaes, Stina Syvänen
Pathophysiological impairment of the neurovascular unit, including the integrity and dynamics of the blood-brain barrier (BBB), has been denoted both a cause and consequence of neurodegenerative diseases. Pathological impact on BBB drug delivery has also been debated. The aim of the present study was to investigate BBB drug transport, by determining the unbound brain-to-plasma concentration ratio (Kp,uu,brain), in aged AβPP-transgenic mice, α-synuclein transgenic mice, and wild type mice. Mice were dosed with a cassette of five compounds, including digoxin, levofloxacin (1 mg/kg, s...
August 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28790893/brain-and-peripheral-atypical-inflammatory-mediators-potentiate-neuroinflammation-and-neurodegeneration
#7
REVIEW
Duraisamy Kempuraj, Ramasamy Thangavel, Govindhasamy P Selvakumar, Smita Zaheer, Mohammad E Ahmed, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Prashant A Natteru, Shankar Iyer, Asgar Zaheer
Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28769926/serum-neuroinflammatory-disease-induced-central-nervous-system-proteins-predict-clinical-onset-of-experimental-autoimmune-encephalomyelitis
#8
Itay Raphael, Johanna Webb, Francisco Gomez-Rivera, Carol A Chase Huizar, Rishein Gupta, Bernard P Arulanandam, Yufeng Wang, William E Haskins, Thomas G Forsthuber
There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood-brain barrier (BBB) is tightly regulated, whereas, in MS, central nervous system (CNS) inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28764938/neuroimaging-techniques-to-assess-inflammation-in-multiple-sclerosis
#9
REVIEW
Silvia Tommasin, Costanza Giannì, Laura De Giglio, Patrizia Pantano
Multiple Sclerosis (MS) is a chronic neurological disease that represents a leading cause of disability in young adults and is characterized by inflammation and degeneration of both white matter (WM) and gray matter (GM). Defining the presence or absence of inflammation on individual basis is a key point in choosing the therapy and monitoring the treatment response. Magnetic resonance imaging (MRI) represents the most sensitive non-invasive tool to monitor inflammation in the clinical practice. Indeed, in the early phase of inflammation MRI detects new lesions as extrusion of gadolinium contrast agents across the altered blood-brain-barrier (BBB)...
July 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28760594/s-oxiracetam-protect-against-ischemic-stroke-via-alleviating-blood-brain-barrier-dysfunction-in-rats
#10
Liangliang Huang, Erxin Shang, Wenxiang Fan, Xiang Li, Binbin Li, Shucheng He, Yuxin Fu, Yizhi Zhang, Yunman Li, Weirong Fang
The blood brain barrier (BBB) maintains the basic stability of the brain tissue under physiological conditions, while destroys and exaggerates brain edema and inflammatory response after ischemic stroke. In this study, we researched S-oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects against ischemic stroke in rats. Middle cerebral artery occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour after reperfusion, rats are administered intravenously with different dose (0...
July 29, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28740568/methane-suppresses-microglial-activation-related-to-oxidative-inflammatory-and-apoptotic-injury-during-spinal-cord-injury-in-rats
#11
WeiHeng Wang, Xiaodong Huang, Jian Li, Aijun Sun, Jiangming Yu, Ning Xie, YanHai Xi, Xiaojian Ye
OBJECTIVE: We investigated the hypothesis that methane-rich saline (MS) can be used to repair spinal cord injury (SCI) in a rat model through suppressing microglial activation related to oxidative, inflammatory, and apoptotic injury. METHODS: MS was injected intraperitoneally in rats after SCI. Hematoxylin-eosin (HE) staining, oxidative stress, inflammatory parameters, and cell apoptosis were detected 72 h after SCI to determine the optimal dose. Then, we investigated the protective mechanisms and the long-term effects of MS on SCI...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28738875/effects-of-fty720-on-brain-neurogenic-niches-in-vitro-and-after-kainic-acid-induced-injury
#12
Raffaela Cipriani, Juan Carlos Chara, Alfredo Rodríguez-Antigüedad, Carlos Matute
BACKGROUND: FTY720 (fingolimod, Gilenya™) is an oral, blood-brain barrier (BBB)-passing drug approved as immunomodulatory treatment for relapsing-remitting form of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the central nervous system (CNS), ranging from neuroprotection to reduction of neuroinflammation. However, the neurogenic and oligodendrogenic potential of FTY720 has been poorly investigated. In this study, we assessed the effect of FTY720 on the production of new neurons and oligodendrocytes from neural stem/precursor cells both in vitro and in vivo...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28737509/astrocytic-tight-junctions-control-inflammatory-cns-lesion-pathogenesis
#13
Sam Horng, Anthony Therattil, Sarah Moyon, Alexandra Gordon, Karla Kim, Azeb Tadesse Argaw, Yuko Hara, John N Mariani, Setsu Sawai, Per Flodby, Edward D Crandall, Zea Borok, Michael V Sofroniew, Candice Chapouly, Gareth R John
Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted by reactive astrocytes open the BBB by disrupting endothelial tight junctions (TJs), but the mechanisms that control access across the GL are unknown. Here, we report that in inflammatory lesions, a second barrier composed of reactive astrocyte TJs of claudin 1 (CLDN1), CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#14
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28701209/alantolactone-a-natural-sesquiterpene-lactone-has-potent-antitumor-activity-against-glioblastoma-by-targeting-ikk%C3%AE-kinase-activity-and-interrupting-nf-%C3%AE%C2%BAb-cox-2-mediated-signaling-cascades
#15
Xun Wang, Zhenlong Yu, Chao Wang, Wei Cheng, Xiangge Tian, Xiaokui Huo, Yan Wang, Chengpeng Sun, Lei Feng, Jinshan Xing, Yulong Lan, Dongdong Sun, Qingjuan Hou, Baojing Zhang, Xiaochi Ma, Bo Zhang
BACKGROUND: Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood...
July 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28687012/value-of-quantitative-magnetic-resonance-imaging-t1-relaxometry-in-predicting-contrast-enhancement-in-glioblastoma-patients
#16
Elke Hattingen, Andreas Müeller, Alina Jurcoane, Burkhard Mädler, Philip Ditter, Hans Schild, Ulrich Herrlinger, Martin Glas, Sied Kebir
The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652141/andrographolide-loaded-nanoparticles-for-brain-delivery-formulation-characterisation-and-in-vitro-permeability-using-hcmec-d3-cell-line
#17
Clizia Guccione, Mouhssin Oufir, Vieri Piazzini, Daniela Elisabeth Eigenmann, Evelyn Andrea Jähne, Volha Zabela, Maria Teresa Faleschini, Maria Camilla Bergonzi, Martin Smiesko, Matthias Hamburger, Anna Rita Bilia
Andrographolide (AG) is a major diterpenoid of the Asian medicinal plant Andrographis paniculata which has shown exciting pharmacological potential for the treatment of inflammation-related pathologies including neurodegenerative disorders. Conversely, the low bioavailability of AG still represents a limiting factor for its use. To overcome these limitations, AG was loaded into human serum albumin based nanoparticles (HSA NPs) and poly ethylcyanoacrylate nanoparticles (PECA NPs). HSA NPs were prepared by thermal (HSAT AG NPs) and chemical cross-linking (HSAC AG NPs), while PECA AG NPs were produced by emulsion-polymerization...
October 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28620801/fty720-attenuates-infection-induced-enhancement-of-a%C3%AE-accumulation-in-app-ps1-mice-by-modulating-astrocytic-activation
#18
Róisín M McManus, Orla M Finucane, Mieszko M Wilk, Kingston H G Mills, Marina A Lynch
It is well established that infection has a significant detrimental effect on patients with Alzheimer's disease (AD), accelerating cognitive decline and, even in healthy ageing individuals, increasing amyloid-β (Aβ) accumulation in the brain. In animal models of AD infection can also cause damage, with evidence of increased neuroinflammation, amyloid pathology and deterioration of cognitive function. These changes are against a backdrop of an age- and AD-related increase in susceptibility to infection. Here we set out to determine whether FTY720, a molecule that binds sphingosine-1-phosphate (S1P) receptors and with known immunosuppressant effects mediating its therapeutic action in multiple sclerosis (MS), might modulate the impact of infection in a mouse model of AD...
June 15, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28619424/cerebrospinal-fluid-and-serum-levels-of-interleukin-8-in-patients-with-multiple-sclerosis-and-its-correlation-with-q-albumin
#19
Z Matejčíková, J Mareš, V Sládková, T Svrčinová, J Vysloužilová, J Zapletalová, P Kaňovský
INTRODUCTION: Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS). Autoimmune inflammation is common in the early stages of MS and is followed by neurodegenerative processes. The result of these changes is axon and myelin breakdown. The paraclinical examination methods are an important part of the diagnostic process. Magnetic resonance imaging of the brain and the cervical spinal cord and an examination of cerebrospinal fluid (CSF) are common paraclinical examinations...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28615922/influence-of-circulating-endothelin-1-and-asymmetric-dimethylarginine-on-whole-brain-circulation-time-in-multiple-sclerosis
#20
Lucia Monti, Lucia Morbidelli, Lorenzo Bazzani, Alessandro Rossi
Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay...
2017: Biomarker Insights
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