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https://www.readbyqxmd.com/read/28180112/oral-multiple-sclerosis-drugs-inhibit-the-in-vitro-growth-of-epsilon-toxin-producing-gut-bacterium-clostridium-perfringens
#1
Kareem R Rumah, Timothy K Vartanian, Vincent A Fischetti
There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two of these medications, Fingolimod, and Teriflunomide, are considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought to trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from the gut bacterium, Clostridium perfringens, may initiate newly forming MS lesions due to its tropism for blood-brain barrier (BBB) vasculature and central nervous system myelin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28165806/enhancing-both-oral-bioavailability-and-brain-penetration-of-puerarin-using-borneol-in-combination-with-preparation-technologies
#2
Tao Yi, Dandan Tang, Fan Wang, Jiqiong Zhang, Jiao Zhang, Jirui Wang, Xiaoyu Xu, Jifen Zhang
Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain-blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28137846/endothelial-wnt-%C3%AE-catenin-signaling-reduces-immune-cell-infiltration-in-multiple-sclerosis
#3
Justin E Lengfeld, Sarah E Lutz, Julian R Smith, Claudiu Diaconu, Cameron Scott, Sigal B Kofman, Claire Choi, Craig M Walsh, Cedric S Raine, Ilir Agalliu, Dritan Agalliu
Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28087417/culture-media-based-selection-of-endothelial-cells-pericytes-and-perivascular-resident-macrophage-like-melanocytes-from-the-young-mouse-vestibular-system
#4
Jinhui Zhang, Songlin Chen, Jing Cai, Zhiqiang Hou, Xiaohan Wang, Allan Kachelmeier, Xiaorui Shi
The vestibular blood-labyrinth barrier (BLB) is comprised of perivascular-resident macrophage-like melanocytes (PVM/Ms) and pericytes (PCs), in addition to endothelial cells (ECs) and basement membrane (BM), and bears strong resemblance to the cochlear BLB in the stria vascularis. Over the past few decades, in vitro cell-based models have been widely used in blood-brain barrier (BBB) and blood-retina barrier (BRB) research, and have proved to be powerful tools for studying cell-cell interactions in their respective organs...
January 11, 2017: Hearing Research
https://www.readbyqxmd.com/read/28060303/an-in-vitro-model-of-the-blood-brain-barrier-using-impedance-spectroscopy-a-focus-on-t-cell-endothelial-cell-interaction
#5
Ivan Kuzmanov, Alexander M Herrmann, Hans-Joachim Galla, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This process is characterized by the transmigration of activated T cells across brain endothelial cells (ECs), the main constituents of the BBB. However, the consequences on brain EC function upon interaction with such T cells are largely unknown. Here we describe an assay that allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function and barrier integrity during the interaction with T cells over time...
December 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28017889/blood-brain-barrier-penetrating-amphiphilic-polymer-nanoparticles-deliver-docetaxel-for-the-treatment-of-brain-metastases-of-triple-negative-breast-cancer
#6
Chunsheng He, Ping Cai, Jason Li, Tian Zhang, Lucy Lin, Azhar Z Abbasi, Jeffrey T Henderson, Andrew Michael Rauth, Xiao Yu Wu
Brain metastasis is a fatal disease with limited treatment options and very short survival. Although systemic chemotherapy has some effect on peripheral metastases of breast cancer, it is ineffective in treating brain metastasis due largely to the blood-brain barrier (BBB). Here we developed a BBB-penetrating amphiphilic polymer-lipid nanoparticle (NP) system that efficiently delivered anti-mitotic drug docetaxel (DTX) for the treatment of brain metastasis of triple negative breast cancer (TNBC). We evaluated the biodistribution, brain accumulation, pharmacokinetics and efficacy of DTX-NP in a mouse model of brain metastasis of TNBC...
December 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28011382/multiple-sclerosis-therapeutic-applications-of-advancing-drug-delivery-systems
#7
REVIEW
Sanam Dolati, Zohreh Babaloo, Farhad Jadidi-Niaragh, Hormoz Ayromlou, Sanam Sadreddini, Mehdi Yousefi
Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27986224/altered-blood-brain-barrier-transport-in-neuro-inflammatory-disorders
#8
REVIEW
Geert J Schenk, Helga E de Vries
During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases...
June 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27906525/the-clinical-utility-of-qsm-disease-diagnosis-medical-management-and-surgical-planning
#9
REVIEW
Sarah Eskreis-Winkler, Yan Zhang, Jingwei Zhang, Zhe Liu, Alexey Dimov, Ajay Gupta, Yi Wang
Quantitative susceptibility mapping (QSM) is an MR technique that depicts and quantifies magnetic susceptibility sources. Mapping iron, the dominant susceptibility source in the brain, has many important clinical applications. Herein, we review QSM applications in the diagnosis, medical management, and surgical treatment of disease. To assist in early disease diagnosis, QSM can identify elevated iron levels in the motor cortex of amyotrophic lateral sclerosis patients, in the substantia nigra of Parkinson's disease (PD) patients, in the globus pallidus, putamen, and caudate of Huntington's disease patients, and in the basal ganglia of Wilson's disease patients...
December 1, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27796269/astrocyte-mediated-regulation-of-multidrug-resistance-p-glycoprotein-in-fetal-and-neonatal-brain-endothelial-cells-age-dependent-effects
#10
Stephanie Baello, Majid Iqbal, William Gibb, Stephen G Matthews
Brain endothelial cells (BECs) form a major component of the blood-brain barrier (BBB). In late gestation, these cells express high levels of the multidrug transporter p-glycoprotein (P-gp; encoded by Abcb1), which prevents the passage of an array of endogenous factors and xenobiotics into the fetal brain. P-gp levels in the BECs increase dramatically in late gestation, coincident with astrocyte differentiation. However, the role of astrocytes in modulating P-gp in the developing BBB is unknown. We hypothesized that factors produced by astrocytes positively regulate P-gp in BECs...
August 2016: Physiological Reports
https://www.readbyqxmd.com/read/27789044/the-effects-of-oxygen-on-ultrasound-induced-blood-brain-barrier-disruption-in-mice
#11
Nathan McDannold, Yongzhi Zhang, Natalia Vykhodtseva
Numerous researchers are investigating the use of microbubble-enhanced ultrasound to disrupt the blood-brain barrier (BBB) and deliver drugs to the brain. This study investigated the impact of using oxygen as a carrier gas for anesthesia on microbubble activity and BBB disruption. Targets in mice were sonicated in combination with administration of Optison microbubbles (100 μL/kg) under isoflurane anesthesia with either oxygen or medical air. A 690-kHz focused ultrasound transducer applied 10-ms bursts at peak pressure amplitudes of 0...
February 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/27774592/rifampicin-attenuates-experimental-autoimmune-encephalomyelitis-by-inhibiting-pathogenic-th17-cells-responses
#12
Ke Ma, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis. Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27774265/ventricular-conduction-abnormalities-as-predictors-of-long-term-survival-in-acute-de-novo-and-decompensated-chronic-heart-failure
#13
Heli Tolppanen, Krista Siirila-Waris, Veli-Pekka Harjola, David Marono, Jiri Parenica, Philipp Kreutzinger, Tuomo Nieminen, Marie Pavlusova, Tuukka Tarvasmaki, Raphael Twerenbold, Jukka Tolonen, Roman Miklik, Markku S Nieminen, Jindrich Spinar, Christian Mueller, Johan Lassus
AIMS: Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long-term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). METHODS AND RESULTS: We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3...
March 2016: ESC Heart Failure
https://www.readbyqxmd.com/read/27682231/increased-cerebrospinal-fluid-metalloproteinase-2-and-interleukin-6-are-associated-with-albumin-quotient-in-neuromyelitis-optica-their-possible-role-on-blood-brain-barrier-disruption
#14
Tomohiko Uchida, Masahiro Mori, Akiyuki Uzawa, Hiroki Masuda, Mayumi Muto, Ryohei Ohtani, Satoshi Kuwabara
BACKGROUND: Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood-brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown. OBJECTIVE: We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO...
September 28, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27659108/inflammation-at-the-blood-brain-barrier-the-role-of-liver-x-receptors
#15
N M de Wit, J Vanmol, A Kamermans, Jja Hendriks, H E de Vries
The blood-brain barrier (BBB) is indispensable for the maintenance of brain homeostasis and proper neuronal functioning. Dysfunction of the BBB significantly contributes to the pathogenesis of neuroinflammatory and neurodegenerative diseases like stroke, multiple sclerosis (MS), and Alzheimer's disease (AD). The neuroinflammatory environment that characterizes these disorders propagates chronic impaired function of the BBB, processes that will be discussed in this review. Limiting dysfunction of the BBB may be an attractive target for treatment of neurological disorders...
September 20, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27592255/blood-brain-barrier-specific-permeability-assay-reveals-n-methylated-tyramine-derivatives-in-standardised-leaf-extracts-and-herbal-products-of-ginkgo-biloba
#16
Árpád Könczöl, Kata Rendes, Miklós Dékány, Judit Müller, Eszter Riethmüller, György Tibor Balogh
The linkage between the central nervous system availability and neuropharmacological activity of the constituents of Ginkgo biloba L. extracts (GBE) is still incomplete. In this study, the in vitro blood-brain barrier (BBB) permeability profile of the standardised GBE was investigated by the parallel artificial membrane permeability assay (PAMPA). Biomarkers, such as terpene trilactones, flavonoid aglycones and ginkgotoxin exerted moderate or good BBB-permeability potential (BBB+), while glycosides and biflavones were predicted as unable to pass the BBB...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27591257/neuropilin-1-modulates-interferon-%C3%AE-stimulated-signaling-in-brain-microvascular-endothelial-cells
#17
Ying Wang, Ying Cao, Ashutosh K Mangalam, Yong Guo, Reghann G LaFrance-Corey, Jeffrey D Gamez, Pascal Aliihnui Atanga, Benjamin D Clarkson, Yuebo Zhang, Enfeng Wang, Ramcharan Singh Angom, Kirthica Dutta, Baoan Ji, Istvan Pirko, Claudia F Lucchinetti, Charles L Howe, Debabrata Mukhopadhyay
Inflammatory response of blood-brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27575893/solid-lipid-nanoparticles-surface-modified-with-anti-contactin2-or-anti-neurofascin-for-brain-targeted-delivery-of-medicines
#18
Nargess Gandomi, Reyhaneh Varshochian, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Mohammad Sharifzadeh, Mohsen Amini, Rassoul Dinarvand
Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammation. Efficient drug delivery to brain is however hampered by blood brain barrier (BBB). In order to have highly efficient and safe delivery of drugs to brain, solid lipid nanoparticles (SLNs) have indicated promising potentials as smart carriers that can pass the blood brain barrier and deliver therapeutic biomolecules to the brain. In this study pegylated SLNs surface modified with using anti-Contactin2 or anti-Neurofascin, two axo-glial-glycoprotein antigens located in node of Ranvier, were prepared...
August 30, 2016: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/27535376/resveratrol-defends-blood-brain-barrier-integrity-in-experimental-autoimmune-encephalomyelitis-mice
#19
Dong Wang, Shi-Ping Li, Jin-Sheng Fu, Sheng Zhang, Lin Bai, Li Guo
The mouse autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), is primarily characterized as dysfunction of the blood-brain barrier (BBB). Resveratrol exhibits anti-inflammatory, antioxidative, and neuroprotective activities. We investigated the beneficial effects of resveratrol in protecting the integrity of the BBB in EAE mice and observed improved clinical outcome in the EAE mice after resveratrol treatment. Evans blue (EB) extravasation was used to detect the disruption of BBB...
November 1, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27533485/hilic-and-erlic-enrichment-of-glycopeptides-derived-from-breast-and-brain-cancer-cells
#20
Lauren G Zacharias, Alyssa K Hartmann, Ehwang Song, Jingfu Zhao, Rui Zhu, Parvin Mirzaei, Yehia Mechref
Aberrant glycosylation has been linked to many different cancer types. The blood-brain barrier (BBB) is a region of the brain that regulates the entrance of ions, diseases, toxins, and so on. However, in breast cancer metastasis, the BBB fails to prevent the crossing of the cancer cells into the brain. Here we present a study of identifying and quantifying the glycosylation of six breast and brain cancer cell lines using hydrophilic interaction liquid chromatography (HILIC) and electrostatic repulsion liquid chromatography (ERLIC) enrichments and LC-MS/MS analysis...
October 7, 2016: Journal of Proteome Research
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