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Microvascular disease of the brain

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https://www.readbyqxmd.com/read/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#1
Stephanie A Newman, Yijun Pan, Jennifer L Short, Joseph A Nicolazzo
In addition to extruding drugs from the brain, P-glycoprotein (P-gp) at the blood-brain barrier (BBB) facilitates the brain-to-blood clearance of β-amyloid (Aβ) and is down-regulated in Alzheimer's disease (AD). Studies suggest that the mood-stabilising drug lithium exerts a protective effect against AD. While the mechanisms underlying this effect are not fully understood, evidence suggests that lithium chloride (LiCl) increases P-gp expression in vitro, albeit at concentrations substantially outside the therapeutic window...
January 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28089903/advances-in-mr-angiography-with-7t-mri-from-microvascular-imaging-to-functional-angiography
#2
Chan-A Park, Chang-Ki Kang, Young-Bo Kim, Zang-Hee Cho
Over the past few decades, vascular flow-dependent imaging techniques have proven to be effective for the visualization of large vessel diseases. However, these approaches are unlikely to be efficacious for small vessels because the affected small vessels cannot always be visualized directly, owing to a lack of detection sensitivity. Recently, many researchers have introduced state-of-the-art imaging techniques to visualize cerebral microvessels using ultra-high-field (UHF) magnetic resonance angiography (MRA)...
January 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28077357/triglyceride-rich-lipoprotein-lipolysis-products-increase-blood-brain-barrier-transfer-coefficient-and-induce-astrocyte-lipid-droplets-and-cell-stress
#3
Linda L Lee, Hnin Hnin Aung, Dennis W Wilson, Steven E Anderson, John C Rutledge, Jennifer M Rutkowsky
Elevation of blood triglycerides, primarily as triglyceride-rich lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer's disease (AD). Brain microvascular endothelial cells and astrocytes, two cell components of the neurovascular unit, participate in controlling blood-brain barrier (BBB) permeability and regulating neurovascular unit homeostasis. Our studies showed that infusion of high physiological concentrations of TGRL lipolysis products (TGRL + lipoprotein lipase) activate and injure brain endothelial cells and transiently increases the BBB transfer coefficient (Ki=permeability x surface area/volume) in vivo...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28062571/performance-of-a-condensed-protocol-that-reduces-effort-and-cost-of-nia-aa-guidelines-for-neuropathologic-assessment-of-alzheimer-disease
#4
Margaret E Flanagan, Desiree A Marshall, Jane B Shofer, Kathleen S Montine, Peter T Nelson, Thomas J Montine, C Dirk Keene
Concerns regarding resource expenditures have been expressed about the 2012 NIA-AA Sponsored Guidelines for neuropathologic assessment of Alzheimer disease (AD) and related dementias. Here, we investigated a cost-reducing Condensed Protocol and its effectiveness in maintaining the diagnostic performance of Guidelines in assessing AD, Lewy body disease (LBD), microvascular brain injury, hippocampal sclerosis (HS), and congophilic amyloid angiopathy (CAA). The Condensed Protocol consolidates the same 20 regions into 5 tissue cassettes at ∼75% lower cost...
January 6, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#5
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
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
#6
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/28053670/the-complete-genome-sequence-of-cronobacter-sakazakii-atcc-29544-t-a-food-borne-pathogen-isolated-from-a-child-s-throat
#7
Seongok Kim, You-Tae Kim, Hyunjin Yoon, Ju-Hoon Lee, Sangryeol Ryu
BACKGROUND: Cronobacter sakazakii is an emerging opportunistic pathogen that is associated with rare but life-threatening cases of severe diseases: meningitis, necrotizing enterocolitis, and sepsis in premature and full-term infants. However, the pathogenesis mechanism of this pathogen remains largely unknown. To determine its pathogenesis at the genomic level, the genome of C. sakazakii ATCC 29544(T) was completely sequenced and analyzed. RESULTS: The genomic DNA, containing a circular chromosome and three plasmids, is composed of 4,511,265 bp with a GC content of 56...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28011167/trypanosoma-brucei-brucei-traverses-different-biological-barriers-differently-and-may-modify-the-host-plasma-membrane-in-the-process
#8
Monica Namayanja, Yan Dai, Barbara Nerima, Enock Matovu, Zhao-Rong Lun, George W Lubega, Chen Zhengjun
Trypanosoma brucei are extracellular hemoflagellate protozoan parasites and one of the causative agents of a devastating zoonotic disease called African Trypanosomiasis. In humans, the disease is caused by Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense, which cross the blood brain barrier (BBB) causing neurological disorders which culminate in death if untreated. In some domestic animals and laboratory rodents, Trypanosoma brucei brucei causes a disease similar to that in humans. The mechanism by which Trypanosoma brucei brucei invade biological barriers including the BBB has not been fully elucidated...
December 20, 2016: Experimental Parasitology
https://www.readbyqxmd.com/read/27988872/insulin-resistance-and-neurodegeneration-progress-towards-the-development-of-new-therapeutics-for-alzheimer-s-disease
#9
REVIEW
Suzanne M de la Monte
Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression...
December 17, 2016: Drugs
https://www.readbyqxmd.com/read/27988246/identification-of-neuronal-and-angiogenic-growth-factors-in-an-in-vitro-blood-brain-barrier-model-system-relevance-in-barrier-integrity-and-tight-junction-formation-and-complexity
#10
Christian Freese, Sanshiro Hanada, Petra Fallier-Becker, C James Kirkpatrick, Ronald E Unger
We previously demonstrated that the co-cultivation of endothelial cells with neural cells resulted in an improved integrity of the in vitro blood-brain barrier (BBB), and that this model could be useful to evaluate the transport properties of potential central nervous system disease drugs through the microvascular brain endothelial. In this study we have used real-time PCR, fluorescent microscopy, protein arrays and enzyme-linked immunosorbent assays to determine which neural- and endothelial cell-derived factors are produced in the co-culture and improve the integrity of the BBB...
December 15, 2016: Microvascular Research
https://www.readbyqxmd.com/read/27986226/glutathione-conjugation-dose-dependently-increases-brain-specific-liposomal-drug-delivery-in-vitro-and-in-vivo
#11
REVIEW
David Maussang, Jaap Rip, Joan van Kregten, Angelique van den Heuvel, Susanne van der Pol, Burt van der Boom, Arie Reijerkerk, Linda Chen, Marco de Boer, Pieter Gaillard, Helga de Vries
The blood-brain barrier (BBB) represents a major obstacle for the delivery and development of drugs curing brain pathologies. However, this biological barrier presents numerous endogenous specialized transport systems that can be exploited by engineered nanoparticles to enable drug delivery to the brain. In particular, conjugation of glutathione (GSH) onto PEGylated liposomes (G-Technology(®)) showed to safely enhance delivery of encapsulated drugs to the brain. Yet, understanding of the mechanism of action remains limited and full mechanistic understanding will aid in the further optimization of the technology...
June 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27958323/differential-transcription-profiles-of-long-non-coding-rnas-in-primary-human-brain-microvascular-endothelial-cells-in-response-to-meningitic-escherichia-coli
#12
Ruicheng Yang, Fei Huang, Jiyang Fu, Beibei Dou, Bojie Xu, Ling Miao, Wentong Liu, Xiaopei Yang, Chen Tan, Huanchun Chen, Xiangru Wang
Accumulating studies have indicated the influence of long non-coding RNAs (lncRNAs) on various biological processes as well as disease development and progression. However, the lncRNAs involved in bacterial meningitis and their regulatory effects are largely unknown. By RNA-sequencing, the transcriptional profiles of host lncRNAs in primary human brain microvascular endothelial cells (hBMECs) in response to meningitic Escherichia coli were demonstrated. Here, 25,257 lncRNAs were identified, including 24,645 annotated lncRNAs and 612 newly found ones...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27951412/increased-cortical-capillary-transit-time-heterogeneity-in-alzheimer-s-disease-a-dsc-mri-perfusion-study
#13
Simon F Eskildsen, Louise Gyldensted, Kartheeban Nagenthiraja, Rune B Nielsen, Mikkel Bo Hansen, Rikke B Dalby, Jesper Frandsen, Anders Rodell, Carsten Gyldensted, Sune N Jespersen, Torben E Lund, Kim Mouridsen, Hans Brændgaard, Leif Østergaard
Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Aβ in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI)...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27935037/an-isogenic-blood-brain-barrier-model-comprising-brain-endothelial-cells-astrocytes-and-neurons-derived-from-human-induced-pluripotent-stem-cells
#14
Scott G Canfield, Matthew J Stebbins, Bethsymarie Soto Morales, Shusaku W Asai, Gad D Vatine, Clive N Svendsen, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit (NVU). We hypothesized that astrocytes and neurons generated from human induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model...
December 9, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27923786/retinal-microvascular-network-alterations-potential-biomarkers-of-cerebrovascular-and-neural-diseases
#15
Delia Cabrera DeBuc, Gabor Mark Somfai, Akos Koller
Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric and developmental diseases. Thus, non-invasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because of the microvascular network of the retina and brain share in many aspects standard features in development, morphology, function and pathophysiology...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27883015/mr-vascular-fingerprinting-in-stroke-and-brain-tumors-models
#16
B Lemasson, N Pannetier, N Coquery, Ligia S B Boisserand, Nora Collomb, N Schuff, M Moseley, G Zaharchuk, E L Barbier, T Christen
In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869115/cerebral-vascular-amyloid-seeds-drive-amyloid-%C3%AE-protein-fibril-assembly-with-a-distinct-anti-parallel-structure
#17
Feng Xu, Ziao Fu, Sharmila Dass, AnnMarie E Kotarba, Judianne Davis, Steven O Smith, William E Van Nostrand
Cerebrovascular accumulation of amyloid β-protein (Aβ), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease. Familial Aβ mutations, such as Dutch-E22Q and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that serves as a potent driver of vascular cognitive impairment and dementia. The distinctive features of vascular amyloid that underlie its unique pathological properties remain unknown. Here, we use transgenic mouse models producing CAA mutants (Tg-SwDI) or overproducing human wild-type Aβ (Tg2576) to demonstrate that CAA-mutant vascular amyloid influences wild-type Aβ deposition in brain...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27863376/cxcr4-increases-in-vivo-glioma-perivascular-invasion-and-reduces-radiation-induced-apoptosis-a-genetic-knockdown-study
#18
Viveka Nand Yadav, Daniel Zamler, Gregory J Baker, Padma Kadiyala, Anat Erdreich-Epstein, Ana C DeCarvalho, Tom Mikkelsen, Maria G Castro, Pedro R Lowenstein
Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion, autovascularization and vascular co-option occur throughout the disease and lead to tumor invasion and progression. The molecular basis for perivascular invasion, i.e., the interaction of glioma tumor cells with endothelial cells is not well characterized. Recent studies indicate that glioma cells have increased expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular invasion of glioma cells using shRNA-mediated knock down of CXCR4...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856004/microbleeds-and-cavernomas-after-radiotherapy-for-paediatric-primary-brain-tumours
#19
João Passos, Hipólito Nzwalo, Mariana Valente, Joana Marques, Ana Azevedo, Eduardo Netto, António Mota, Alexandra Borges, Sofia Nunes, Duarte Salgado
BACKGROUND: With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST. OBJECTIVE: To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27846787/cryopreservation-of-brain-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells-is-enhanced-by-rho-associated-coiled-coil-containing-kinase-inhibition
#20
Hannah K Wilson, Madeline G Faubion, Michael K Hjortness, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies...
December 2016: Tissue Engineering. Part C, Methods
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