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Ma Ke, 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 for myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis (MS). 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...
October 23, 2016: Journal of Neurochemistry
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
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
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
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
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
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
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, anti-oxidative 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...
August 17, 2016: Journal of Neurophysiology
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
Xiaojian Shao, Dan Gao, Yongli Chen, Feng Jin, Guangnan Hu, Yuyang Jiang, Hongxia Liu
Since most of the central nervous system (CNS) drug candidates show poor permeability across the blood-brain barrier (BBB), development of a reliable platform for permeability assay will greatly accelerate drug discovery. Herein, we constructed a microfluidic BBB model to mimic drug delivery into the brain to induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties, human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured in a membrane-based microchannel. Sunitinib, a model drug, was then delivered into the microchannel and forced to permeate through the BBB model...
August 31, 2016: Analytica Chimica Acta
Lieselotte Veryser, Nathalie Bracke, Evelien Wynendaele, Tanmayee Joshi, Pratima Tatke, Lien Taevernier, Bart De Spiegeleer
Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS(2) method was used to quantify pellitorine. Results...
2016: BioMed Research International
Min Jung Lee, So Jin Bing, Jonghee Choi, Minhee Jang, Gihyun Lee, Hyunkyoung Lee, Byung Soo Chang, Youngheun Jee, Sung Joong Lee, Ik-Hyun Cho
BACKGROUND: The inflammatory myeloid cell activation is one of the hallmarks of experimental autoimmune encephalomyelitis (EAE), yet the in vivo role of the inflammatory myeloid cell activation in EAE has not been clearly resolved. It is well-known that IKK/NF-κB is a key signaling pathway that regulates inflammatory myeloid activation. METHODS: We investigated the in vivo role of inflammatory myeloid cell activation in myelin oligodendrocyte glycoprotein (MOG) peptides-induced EAE using myeloid cell type-specific ikkβ gene conditional knockout-mice (LysM-Cre/Ikkβ (F/F) )...
2016: Molecular Neurodegeneration
Priscila S Souza, Elaine D Gonçalves, Giulia S Pedroso, Hemelin R Farias, Stella C Junqueira, Rodrigo Marcon, Talita Tuon, Maíra Cola, Paulo C L Silveira, Adair R Santos, João B Calixto, Cláudio T Souza, Ricardo A de Pinho, Rafael C Dutra
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS...
July 22, 2016: Molecular Neurobiology
Gianni Pastore, Massimiliano Maines, Lina Marcantoni, Francesco Zanon, Franco Noventa, Giorgio Corbucci, Enrico Baracca, Silvio Aggio, Claudio Picariello, Daniela Lanza, Gianluca Rigatelli, Mauro Carraro, Loris Roncon, S Serge Barold
BACKGROUND: Estimating left ventricular electrical delay (Q-LV) from a 12-lead ECG may be important in evaluating cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess the impact of Q-LV interval on ECG configuration. METHODS: One hundred ninety-two consecutive patients undergoing CRT implantation were divided electrocardiographically into 3 groups: left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (IVCD)...
July 14, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Michael J Lang, Ruihe Lin, Ashwini Dayal Sharan, Robert H Rosenwasser, Lorraine Iacovitti
INTRODUCTION: The presence of the blood-brain barrier (BBB) in vertebrates is a major limitation to the delivery of therapeutic agents into brain tissue. Mesenchymal stem cell (MSC) infusion has been shown to reduce stroke volume and improve recovery, but the BBB limits cellular engraftment. Sphenopalatine ganglion (SPG) stimulation has been shown to transiently increase BBB permeability. A rodent model was designed to test the hypothesis that SPG stimulation enhances the effect of MSC infusion...
August 2016: Neurosurgery
Y Zhang, S A Gauthier, A Gupta, L Tu, J Comunale, G C-Y Chiang, W Chen, C A Salustri, W Zhu, Y Wang
BACKGROUND AND PURPOSE: Magnetic susceptibility values of multiple sclerosis lesions increase as they change from gadolinium-enhancing to nonenhancing. Can susceptibility values measured on quantitative susceptibility mapping without gadolinium injection be used to identify the status of lesion enhancement in surveillance MR imaging used to monitor patients with MS? MATERIALS AND METHODS: In patients who had prior MR imaging and quantitative susceptibility mapping in a current MR imaging, new T2-weighted lesions were evaluated for enhancement on conventional T1-weighted imaging with gadolinium, and their susceptibility values were measured on quantitative susceptibility mapping...
June 30, 2016: AJNR. American Journal of Neuroradiology
Lien Taevernier, Nathalie Bracke, Lieselotte Veryser, Evelien Wynendaele, Bert Gevaert, Kathelijne Peremans, Bart De Spiegeleer
The cyclic depsipeptide mycotoxins beauvericin and enniatins are capable of reaching the systemic circulation through various routes of exposure and are hence capable of exerting central nervous system (CNS) effects, if they are able to pass the blood-brain barrier (BBB), which was the main objective of this study. Quantification of the mycotoxins was performed using an in-house developed and validated bio-analytical UHPLC-MS/MS method. Prior to the BBB experiments, the metabolic stability of the mycotoxins was evaluated in vitro in mouse serum and brain homogenate...
September 6, 2016: Toxicology Letters
Hideaki Nishihara, Fumitaka Shimizu, Takao Kitagawa, Nanami Yamanaka, Junko Akada, Yasuhiro Kuramitsu, Yasuteru Sano, Yukio Takeshita, Toshihiko Maeda, Masaaki Abe, Michiaki Koga, Kazuyuki Nakamura, Takashi Kanda
BACKGROUND: Recent studies have revealed that the disruption of the blood-brain barrier (BBB) might contribute to the induction of neurodegeneration in the progressive stage of multiple sclerosis (MS). OBJECTIVE: We investigated a potential target for the serum auto-antibodies responsible for the BBB impairment in patients with secondary progressive MS (SPMS). METHODS: We identified undetermined target antigens in human brain microvascular endothelial cells (BMECs) that reacted with auto-antibodies in sera from SPMS patients using a proteomic approach...
June 23, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Henriette Rudolph, Armelle Klopstein, Isabelle Gruber, Claudia Blatti, Ruth Lyck, Britta Engelhardt
Although CD8(+) T cells have been implied in the pathogenesis of multiple sclerosis (MS), the molecular mechanisms mediating CD8(+) T-cell migration across the blood-brain barrier (BBB) into the central nervous system (CNS) are ill defined. Using in vitro live cell imaging, we directly compared the multistep extravasation of activated CD4(+) and CD8(+) T cells across primary mouse brain microvascular endothelial cells (pMBMECs) as a model for the BBB under physiological flow. Significantly higher numbers of CD8(+) than CD4(+) T cells arrested on pMBMECs under noninflammatory and inflammatory conditions...
September 2016: European Journal of Immunology
Wei Xue, Yang Liu, Wen-Yuan Qi, Yan Gao, Min Li, Ai-Xin Shi, Ke-Xin Li
The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models...
June 2016: Journal of Asian Natural Products Research
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