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https://www.readbyqxmd.com/read/28443093/a-novel-cervical-spinal-cord-window-preparation-allows-for-two-photon-imaging-of-t-cell-interactions-with-the-cervical-spinal-cord-microvasculature-during-experimental-autoimmune-encephalomyelitis
#1
Neda Haghayegh Jahromi, Heidi Tardent, Gaby Enzmann, Urban Deutsch, Naoto Kawakami, Stefan Bittner, Dietmar Vestweber, Frauke Zipp, Jens V Stein, Britta Engelhardt
T-cell migration across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Two-photon intravital microscopy (2P-IVM) has been established as a powerful tool to study cell-cell interactions in inflammatory EAE lesions in living animals. In EAE, central nervous system inflammation is strongly pronounced in the spinal cord, an organ in which 2P-IVM imaging is technically very challenging and has been limited to the lumbar spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#2
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28347895/metabolomic-changes-in-rat-model-of-cauda-equina-injury
#3
Yang Liu, Rui Yang, Qingjie Kong, Yuan Wang, Bin Zhang, Jingchuan Sun, Yong Yang, Bing Zheng, Hongbin Yuan, Jiangang Shi
BACKGROUND: To demonstrate the differences of metabolomic changes in a rat model of cauda equina injury (CEI) and find potent metabolic biomarkers of CEI. MATERIAL AND METHODS: A total of 28 Sprague-Dawley (SD) rats were used in this study. After the rats were given anesthesia and fixed in a prone position, a piece of silicone block was placed into the epidural space below the lamina. Behavior tests including the Basso, Beattie, and Bresnahan (BBB) open field locomotor scale and an inclined plane test were conducted 1 day and 2 days after surgery...
March 24, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28287595/bioluminescence-and-near-infrared-imaging-of-optic-neuritis-and-brain-inflammation-in-the-eae-model-of-multiple-sclerosis-in-mice
#4
Katja Schmitz, Irmgard Tegeder
Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing motor function deficits are basic readouts of the immune-mediated inflammation of the spinal cord. However, scores and body weight do not allow for an in vivo assessment of brain inflammation and optic neuritis. The latter is an early and frequent manifestation in about 2/3 of MS patients. Here, we show methods for bioluminescence and near-infrared live imaging to assess EAE evoked optic neuritis, brain inflammation, and blood-brain barrier (BBB) disruption in living mice using an in vivo imaging system...
March 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286112/the-gut-microbiome-and-microbial-translocation-in-multiple-sclerosis
#5
REVIEW
Ali Mirza, Yang Mao-Draayer
Individuals with multiple sclerosis (MS) have a distinct intestinal microbial community (microbiota) and increased low-grade translocation of bacteria from the intestines into the circulation. The observed change of intestinal bacteria in MS patients regulate immune functions involved in MS pathogenesis. These functions include: systemic and central nervous system (CNS) immunity (including peripheral regulatory T cell function), the blood-brain barrier (BBB) permeability and CNS-resident cell activity. This review discusses the MS intestinal microbiota implication on MS systemic- and CNS-immunopathology...
March 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28285073/development-of-an-uplc-ms-ms-method-for-quantification-of-avitinib-ac0010-and-its-five-metabolites-in-human-cerebrospinal-fluid-application-to-a-study-of-the-blood-brain-barrier-penetration-rate-of-non-small-cell-lung-cancer-patients
#6
Weicong Wang, Xin Zheng, Hanping Wang, Lu Wang, Ji Jiang, Pei Hu
Avitinib (AC0010) is a mutant-selective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring EGFR active and T790M resistant mutations. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of Avitinib and its five metabolites (M1, M2, M4, M7, MII-6) in human cerebrospinal fluid (CSF). The samples were purified by protein precipitation and separated on a BEH C18 column (2...
May 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28284329/soluble-cd40-ligand-contributes-to-blood-brain-barrier-breakdown-and-central-nervous-system-inflammation-in-multiple-sclerosis-and-neuromyelitis-optica-spectrum-disorder
#7
Hiroki Masuda, Masahiro Mori, Tomohiko Uchida, Akiyuki Uzawa, Ryohei Ohtani, Satoshi Kuwabara
Soluble CD40 ligand (sCD40L) is reported to disrupt the blood-brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD40L levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD40L levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD40L levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28257578/amelioration-of-experimental-autoimmune-encephalomyelitis-in-mice-by-interferon-beta-gene-therapy-using-a-long-term-expression-plasmid-vector
#8
Atsushi Hamana, Yuki Takahashi, Akane Tanioka, Makiya Nishikawa, Yoshinobu Takakura
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Repeated injections of the interferon-β (IFN-β) protein are required for relapse prevention therapy in patients with MS. IFN-β gene transfer can be an alternative treatment that continuously supplies IFN-β protein to the patient without requiring repeated injections. In a previous study, we constructed a novel long-term IFN-β-expressing plasmid vector (pMx-IFN-β). In the present study, we examined whether gene transfer of pMx-IFN-β could be effective for the treatment of MS in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS...
April 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28238901/evaluation-of-14-c-and-13-c-sucrose-as-blood-brain-barrier-permeability-markers
#9
Mohammad K Miah, Ekram A Chowdhury, Ulrich Bickel, Reza Mehvar
Non-specific quantitation of [(14)C]sucrose in blood and brain has been routinely used as a quantitative measure of the in vivo blood-brain barrier (BBB) integrity. However, the reported apparent brain uptake clearance (Kin) of the marker varies widely (∼100 fold). We investigated the accuracy of the use of the marker in comparison with a stable isotope of sucrose ([(13)C]sucrose) measured by a specific LC-MS/MS method. Rats received single doses of each marker, and the Kin values were determined. Surprisingly, the Kin value of [(13)C]sucrose was 6-7 fold lower than that of [(14)C]sucrose...
February 23, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28238797/in%C3%A2-vitro-modeling-of-blood-brain-barrier-with-human-ipsc-derived-endothelial-cells-pericytes-neurons-and-astrocytes-via-notch-signaling
#10
Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K Yamashita
The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells (BECs), pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs) were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A) and efflux transporters (ABCA1, BCRP, PGP, MRP5), and strong barrier function based on tight junctions...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28236843/multiple-sclerosis-and-air-pollution-exposure-mechanisms-toward-brain-autoimmunity
#11
Sayed Esmaeil Mousavi, Pouria Heydarpour, Jacques Reis, Masoud Amiri, Mohammad Ali Sahraian
The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in multiple sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28180112/oral-multiple-sclerosis-drugs-inhibit-the-in-vitro-growth-of-epsilon-toxin-producing-gut-bacterium-clostridium-perfringens
#12
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
#13
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
#14
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...
February 14, 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
#15
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...
March 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
#16
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
#17
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
#18
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
#19
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
#20
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
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