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Microvascular disease of the brain

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https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#1
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28504673/a-fluoro-nissl-dye-identifies-pericytes-as-distinct-vascular-mural-cells-during-in-vivo-brain-imaging
#2
Eyiyemisi C Damisah, Robert A Hill, Lei Tong, Katie N Murray, Jaime Grutzendler
Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that the fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity, allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular and functional features that do not overlap with precapillary or arteriolar smooth muscle actin-expressing cells...
May 15, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28482008/the-microcirculation-a-key-player-in-obesity-associated-cardiovascular-disease
#3
Oana Sorop, T Dylan Olver, Jens van de Wouw, Ilkka Heinonen, Richard W van Duin, Dirk J Duncker, Daphne Merkus
It is increasingly recognized that obesity is a risk factor for microvascular disease, i.e. results in structural and functional changes in the microvasculature. This review aims to describe how obesity impacts the microvasculature of visceral adipose tissue, skeletal muscle, heart, brain, kidneys and lungs. These changes involve endothelial dysfunction, which in turn impacts control of vascular tone, contributes to development of microvascular insulin resistance, alters secretion of paracrine factors like nitric oxide and endothelin, but also influences vascular structure and perivascular inflammation...
May 8, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#4
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28469997/iqgap1-mediates-hcp1-promoted-escherichia-coli-meningitis-by-stimulating-the-mapk-pathway
#5
Mingna Zhao, Lingfei Zhang, Shaogang Lv, Chenzi Zhang, Lin Wang, Hong Chen, Yan Zhou, Jiatao Lou
Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28469657/fermented-chinese-formula-shuan-tong-ling-attenuates-ischemic-stroke-by-inhibiting-inflammation-and-apoptosis
#6
Zhi-Gang Mei, Ling-Jing Tan, Jin-Feng Wang, Xiao-Li Li, Wei-Feng Huang, Hua-Jun Zhou
The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae (Gegen), salvia miltiorrhiza (Danshen), radix curcuma (Jianghuang), hawthorn (Shanzha), salvia chinensis (Shijianchuan), sinapis alba (Baijiezi), astragalus (Huangqi), panax japonicas (Zhujieshen), atractylodes macrocephala koidz (Baizhu), radix paeoniae alba (Baishao), bupleurum (Chaihu), chrysanthemum (Juhua), rhizoma cyperi (Xiangfu) and gastrodin (Tianma), whose aqueous extract was fermented with lactobacillus, bacillus aceticus and saccharomycetes...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28468844/space-and-location-of-cerebral-microbleeds-cognitive-decline-and-dementia-in-the-community
#7
Jie Ding, Sigurður Sigurðsson, Pálmi V Jónsson, Gudny Eiriksdottir, Osorio Meirelles, Olafur Kjartansson, Oscar L Lopez, Mark A van Buchem, Vilmundur Gudnason, Lenore J Launer
OBJECTIVE: To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people. METHODS: In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5...
May 3, 2017: Neurology
https://www.readbyqxmd.com/read/28466272/bfgf-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-endothelial-monolayer-permeability-via-s1pr1-dependent-mechanisms
#8
Li Lin, Qingzhi Wang, Kenny Qian, Zeyuan Cao, Jian Xiao, Xiaoying Wang, Xiaokun Li, Zhanyang Yu
Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R)...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28453876/age-associated-changes-in-the-blood-brain-barrier-comparative-studies-in-human-and-mouse
#9
Emily F Goodall, Chunfang Wang, Julie E Simpson, David J Baker, David R Drew, Paul R Heath, M Jill Saffrey, Ignacio A Romero, Stephen B Wharton
AIMS: While vascular pathology is a common feature of a range of neurodegenerative diseases, we hypothesised that vascular changes occur in association with normal ageing. Therefore we aimed to characterise age-associated changes in the blood brain barrier (BBB) in human and mouse cohorts. METHODS: Immunohistochemistry and Evans Blue assays were used to characterise BBB dysfunction (tight junction protein expression and serum plasma protein accumulation), vascular pathology (pericyte loss and vascular density) and glial pathology (astrocyte and microglial density) in ageing neurological control human pre-frontal cortex (a total of 23 cases from 5 age groups representing the spectrum of young adult to old age: 20-30yrs, 31-45yrs, 46-60yrs, 61-75yrs and 75+) and C57BL/6 mice (3 month, 12 month, 18 month and 24 month, n=5/6 per group)...
April 28, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28453484/can-better-management-of-periodontal-disease-delay-the-onset-and-progression-of-alzheimer-s-disease
#10
Alice Harding, Sarita Robinson, StJohn Crean, Sim K Singhrao
A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28448020/analysis-of-lymphocyte-extravasation-using-an-in-vitro-model-of-the-human-blood-brain-barrier
#11
Andreas Schulte-Mecklenbeck, Urvashi Bhatia, Tilman Schneider-Hohendorf, Nicholas Schwab, Heinz Wiendl, Catharina C Gross
Lymphocyte extravasation into the central nervous system (CNS) is critical for immune surveillance. Disease-related alterations of lymphocyte extravasation might result in pathophysiological changes in the CNS. Thus, investigation of lymphocyte migration into the CNS is important to understand inflammatory CNS diseases and to develop new therapy approaches. Here we present an in vitro model of the human blood-brain barrier to study lymphocyte extravasation. Human brain microvascular endothelial cells (HBMEC) are confluently grown on a porous polyethylene terephthalate transwell insert to mimic the endothelium of the blood-brain barrier...
April 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447863/lysophosphatidic-acid-and-amitriptyline-signal-through-lpa1r-to-reduce-p-glycoprotein-transport-at-the-blood-brain-barrier
#12
David B Banks, Gary Ny Chan, Rebecca A Evans, David S Miller, Ronald E Cannon
The blood-brain barrier is a microvascular network that (1) provides neuroprotection from metabolic and environmental toxins and (2) limits the delivery of therapeutics to the central nervous system (CNS). The ATP-binding cassette transporter P-glycoprotein contributes to the latter by actively pumping clinical substrates back into circulation before they can reach the brain parenchyma. Targeting P-glycoprotein has proven effective in increasing the delivery of therapeutics to their cerebral targets. We provide a novel mechanism to achieve this end in functioning, intact rat brain capillaries, whereby the bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that requires G-protein coupling, Src kinase, and ERK 1/2...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#13
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28438530/ferulic-acid-attenuates-brain-microvascular-endothelial-cells-damage-caused-by-oxygen-glucose-deprivation-via-punctate-mitochondria-dependent-mitophagy
#14
Jun-Li Chen, Wen-Jun Duan, Si Luo, Shi Li, Xiao-Hui Ma, Bo-Nan Hou, Shu-Yi Cheng, Shu-Huan Fang, Qi Wang, Shui-Qing Huang, Yun-Bo Chen
Ferulic acid (FA) has an important effect on scavenging free radicals, which is related to the alleviation of various neurodegenerative diseases. However, there are few studies about its effects on vascular dementia. In this study, we demonstrated the effect of FA on oxidative damage of brain microvascular endothelial cells (BMECs) which underwent oxygen-glucose deprivation (OGD) for 2 hours. Our data showed that FA significantly reversed the oxidative stress state of OGD-treated BMECs and reduced mitochondrial dysfunction...
April 21, 2017: Brain Research
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#15
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 2017: Aging
https://www.readbyqxmd.com/read/28435263/neuroprotection-against-apoptosis-of-sk-n-mc-cells-using-rmp-7-and-lactoferrin-grafted-liposomes-carrying-quercetin
#16
Yung-Chih Kuo, Chien-Wei Tsao
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28430012/zo-1-expression-is-suppressed-by-gm-csf-via-mir-96-erg-in-brain-microvascular-endothelial-cells
#17
Hu Zhang, Shuhong Zhang, Jilin Zhang, Dongxin Liu, Jiayi Wei, Wengang Fang, Weidong Zhao, Yuhua Chen, Deshu Shang
The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28429235/regulation-of-human-brain-microvascular-endothelial-cell-adhesion-and-barrier-functions-by-memantine
#18
Fei Wang, Zhirong Zou, Yi Gong, Dong Yuan, Xun Chen, Tao Sun
Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α)...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28422124/prevalence-of-type-2-diabetes-and-its-complications-in-india-and-economic-costs-to-the-nation
#19
REVIEW
R Pradeepa, V Mohan
Diabetes, a major lifestyle disorder, has become a global burden, and the prevalence rates are rising steeply in developing economies. Rapid socioeconomic transition with urbanization and industrialization are the main causes for the global diabetes epidemic. Among developing economies, the highest increase in number of people with diabetes is in China followed by India. In India, the epidemic of diabetes continue to increase and is experiencing a shift in diabetes prevalence from urban to rural areas, the affluent to the less privileged and from older to younger people...
April 19, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28420646/associations-between-left-ventricular-dysfunction-and-brain-structure-and-function-findings-from-the-sabre-southall-and-brent-revisited-study
#20
Chloe M Park, Emily D Williams, Nish Chaturvedi, Therese Tillin, Robert J Stewart, Marcus Richards, Dean Shibata, Jamil Mayet, Alun D Hughes
BACKGROUND: Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. METHOD AND RESULTS: A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment...
April 18, 2017: Journal of the American Heart Association
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