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Blood-brain barrier

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https://www.readbyqxmd.com/read/29150289/the-cause-of-multiple-sclerosis-is-autoimmune-attack-of-adenosyltransferase-thereby-limiting-adenosylcobalamin-production
#1
J L Boucher
The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#2
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29147635/global-and-targeted-pathway-impact-of-gliomas-on-white-matter-integrity-based-on-lobar-localization
#3
David R Ormond, Shawn D'Souza, John A Thompson
Primary brain tumors comprise 28% of all tumors and 80% of malignant tumors. Pathophysiology of high-grade gliomas includes significant distortion of white matter architecture, necrosis, the breakdown of the blood brain barrier, and increased intracranial pressure. Diffusion tensor imaging (DTI), a diffusion weighted imaging technique, can be used to assess white matter architecture. Use of DTI as a non-invasive pathophysiological tool to analyze glioma impact on white matter microstructure has yet to be fully explored...
September 7, 2017: Curēus
https://www.readbyqxmd.com/read/29146209/the-blood-brain-barrier-and-braf-inhibitors-implications-for-patients-with-melanoma-brain-metastases
#4
EDITORIAL
Keiran S M Smalley, Peter A Forsyth
No abstract text is available yet for this article.
November 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29146191/automatic-delineation-of-brain-regions-on-mri-and-pet-images-from-the-pig
#5
Jonas Villadsen, Hanne D Hansen, Louise M Jørgensen, Sune H Keller, Flemming L Andersen, Ida N Petersen, Gitte M Knudsen, Claus Svarer
BACKGROUND: The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated. COMPARISON WITH EXISTING METHODS: Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake...
November 13, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29143947/connexin-30-is-expressed-in-a-subtype-of-mouse-brain-pericytes
#6
Noémie Mazaré, Alice Gilbert, Anne-Cécile Boulay, Nathalie Rouach, Martine Cohen-Salmon
Pericytes are mural cells of blood microvessels which play a crucial role at the neurovascular interface of the central nervous system. They are involved in the regulation of blood-brain barrier integrity, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, and neuroinflammation, and they demonstrate stem cell activity. Morphological and molecular studies to characterize brain pericytes recently pointed out some heterogeneity in pericyte population. Nevertheless, a clear definition of pericyte subtypes is still lacking...
November 16, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29142352/localized-pontine-uptake-in-fluorine-18-fuorodeoxyglucose-positron-emission-tomography-computed-tomography-in-a-case-of-hyponatremia-a-case-report-and-review-of-literature
#7
Thangalakshmi Sivathapandi, Shelley Simon, Indirani Elangovan
A rare acquired demyelinating lesion of the pons central pontine myelinolysis (CPM) typically occurs after rapid correction of hyponatremia. There is disruption of blood-brain barrier due to osmotic stress allowing access for inflammatory mediators in extravascular brain tissue, which most likely attracts glial cells of the brain, attracts macrophages, and activates astrocytes. We present a case of female with a known history of inflammatory bowel disease who presented with altered sensorium and hyponatremia...
October 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/29141800/elevated-plasma-fibrinogen-levels-in-multiple-sclerosis-patients-during-relapse
#8
Jahir Miranda Acuña, Milagros Hidalgo de la Cruz, Alberto Lozano Ros, Saskia Prasca Tapia, Maria Luisa Martínez Ginés, Clara Dionisia de Andrés Frutos
Fibrinogen is a protein that plays a key role in blood coagulation and thrombosis and it is involved in several inflammatory processes; in multiple sclerosis (MS) may be related with blood-brain barrier (BBB) disruption. We analysed the relationship between plasma fibrinogen levels and the presence of active lesions on magnetic resonance imaging (MRI) during relapses of multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients. METHODS: We collected data of patients admitted to a tertiary-care hospital with relapse of MS and CIS from 2008 to 2013 and we analysed the relation between plasma fibrinogen levels (normal: 200mg/dl-417mg/dl) and the presence of active lesions on brain or spinal MRI...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#9
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29138458/low-intensity-pulsed-ultrasound-improves-behavioral-and-histological-outcomes-after-experimental-traumatic-brain-injury
#10
Wei-Shen Su, Chun-Hu Wu, Szu-Fu Chen, Feng-Yi Yang
The purpose of this study was to investigate the neuroprotective effects of low-intensity pulsed ultrasound (LIPUS) on behavioral and histological outcomes in a mouse model of traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury were treated with LIPUS in the injured region daily for a period of 4 weeks. The effects of LIPUS on edema were observed by MR imaging in the mouse brain at 1 and 4 days following TBI. Brain water content, blood-brain barrier permeability, histology analysis, and behavioral studies were performed to assess the effects of LIPUS...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138435/effects-of-gsm-and-umts-mobile-telephony-signals-on-neuron-degeneration-and-blood-brain-barrier-permeation-in-the-rat-brain
#11
Florence Poulletier de Gannes, Hiroshi Masuda, Bernard Billaudel, Emmanuelle Poque-Haro, Annabelle Hurtier, Philippe Lévêque, Gilles Ruffié, Murielle Taxile, Bernard Veyret, Isabelle Lagroye
Blood-brain barrier (BBB) permeation and neuron degeneration were assessed in the rat brain following exposure to mobile communication radiofrequency (RF) signals (GSM-1800 and UMTS-1950). Two protocols were used: (i) single 2 h exposure, with rats sacrificed immediately, and 1 h, 1, 7, or 50 days later, and (ii) repeated exposures (2 h/day, 5 days/week, for 4 weeks) with the effects assessed immediately and 50 days after the end of exposure. The rats' heads were exposed at brain-averaged specific absorption rates (BASAR) of 0...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138419/ivig-activates-fc%C3%AE-riib-ship1-pip3-pathway-to-stabilize-mast-cells-and-suppress-inflammation-after-ich-in-mice
#12
Gokce Yilmaz Akyol, Anatol Manaenko, Onat Akyol, Ihsan Solaroglu, Wing Mann Ho, Yan Ding, Jerry Flores, John H Zhang, Jiping Tang
Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src homology 2-containing inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137682/cefepime-induced-neurotoxicity-a-systematic-review
#13
Lauren E Payne, David J Gagnon, Richard R Riker, David B Seder, Elizabeth K Glisic, Jane G Morris, Gilles L Fraser
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations...
November 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29137631/synthetic-oleanane-triterpenoids-enhance-blood-brain-barrier-integrity-and-improve-survival-in-experimental-cerebral-malaria
#14
Valerie M Crowley, Kodjo Ayi, Ziyue Lu, Karen T Liby, Michael Sporn, Kevin C Kain
BACKGROUND: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection associated with high mortality and neurocognitive impairment in survivors. New anti-malarials and host-based adjunctive therapy may improve clinical outcome in CM. Synthetic oleanane triterpenoid (SO) compounds have shown efficacy in the treatment of diseases where inflammation and oxidative stress contribute to pathogenesis. METHODS: A derivative of the SO 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), CDDO-ethyl amide (CDDO-EA) was investigated for the treatment of severe malaria in a pre-clinical model...
November 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29137378/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#15
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of (125)I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136088/abcd1-dysfunction-alters-white-matter-microvascular-perfusion
#16
Arne Lauer, Xiao Da, Mikkel Bo Hansen, Gregoire Boulouis, Yangming Ou, Xuezhu Cai, Afonso Liberato Celso Pedrotti, Jayashree Kalpathy-Cramer, Paul Caruso, Douglas L Hayden, Natalia Rost, Kim Mouridsen, Florian S Eichler, Bruce Rosen, Patricia L Musolino
Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability of the blood-brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic resonance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased capillary flow heterogeneity in asymptomatic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease...
November 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29135325/facile-development-of-nanocomplex-in-nanoparticles-for-enhanced-loading-and-selective-delivery-of-doxorubicin-to-brain
#17
Amr Hefnawy, Islam A Khalil, Ibrahim M El-Sherbiny
AIM: Facile development of polysaccharides-based carrier system for efficient delivery of doxorubicin (DOX) to the brain. METHODS: DOX was nanocomplexed with alginate (Alg) followed by incorporation into chitosan (Cs) nanomatrices. The resulting carriers were optimized to have a net positive charge improving their delivery across the blood-brain barrier. The optimum DOX-loaded nanosystem was targeted to brain tissue via loading into various nasal dosage forms. RESULTS: The pH-dependent ionization of both DOX and Alg was found to have a significant effect on DOX entrapment efficiency which was improved from 4% at slightly acidic media to 85% using different pHs...
November 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29135106/evidence-for-the-efficacy-of-disulfiram-and-copper-combination-in-glioblastoma-multiforme-a-propos-of-a-case
#18
Petros N Karamanakos, Dimitrios T Trafalis, Dionysios J Papachristou, Eleftheria S Panteli, Maria Papavasilopoulou, Andreas Karatzas, Dimitrios Kardamakis, Georgios Nasioulas, Marios Marselos
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134771/detection-of-%C3%AE-amyloid-by-sialic-acid-coated-bovine-serum-albumin-magnetic-nanoparticles-in-a-mouse-model-of-alzheimer-s-disease
#19
Seyedmehdi Hossaini Nasr, Hovig Kouyoumdjian, Christiane Mallett, Sherif Ramadan, David C Zhu, Erik M Shapiro, Xuefei Huang
The accumulation and formation of β-amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSAx -Sia) to overcome the challenges in Aβ imaging in vivo...
November 14, 2017: Small
https://www.readbyqxmd.com/read/29134501/pharmacokinetic-properties-of-saffron-and-its-active-components
#20
Azar Hosseini, Bibi Marjan Razavi, Hossein Hosseinzadeh
Saffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic...
November 13, 2017: European Journal of Drug Metabolism and Pharmacokinetics
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