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Microvascular disease of the brain

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https://www.readbyqxmd.com/read/28628018/autoimmune-limbic-encephalitis-case-reports
#1
K Kobaidze, A Harrison, Y Burklin, V Patidar, M Riccardi
Limbic encephalitis (LE) is an autoimmune or paraneoplastic disease that affects the medial temporal lobes. The patient will usually present with cognitive impairment, psychiatric changes, and seizures. Autoimmune limbic encephalitis (LE) is a challenging diagnosis as it is not always included in the typical paraneoplastic/autoimmune panels. Anti-GAD antibodies are associated with various disease including type I diabetes mellitus, various autoimmune processes, some neoplastic and infectious diseases. Thus, it is not as specific as some of the antibodies causing LE...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28627379/microvascular-changes-in-down-syndrome-with-alzheimer-type-pathology-insights-into-a-potential-vascular-mechanism-for-down-syndrome-and-alzheimer-s-disease
#2
David A Drachman, Thomas W Smith, Bassam Alkamachi, Kevin Kane
INTRODUCTION: The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following β amyloid (Aβ) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. METHODS: We examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology...
June 13, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28626344/increased-transendothelial-transport-of-ccl3-is-insufficient-to-drive-immune-cell-transmigration-through-the-blood-brain-barrier-under-inflammatory-conditions-in-vitro
#3
Maxime De Laere, Carmelita Sousa, Megha Meena, Roeland Buckinx, Jean-Pierre Timmermans, Zwi Berneman, Nathalie Cools
Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood-brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28625785/cerebral-ischemia-repefusion-injury-from-bench-space-to-bedside
#4
REVIEW
Z Nagy, S Nardai
While stroke research represents the primary interface between circulation and brain research, the hemostasis system also carries a pivotal role in the mechanism of vascular brain injury. The complex interrelated events triggered by the energy crisis have a specific spatial and temporal pattern arching from the initial damage to the final events of brain repair. The complexity of the pathophysiology make it difficult to model this disease, therefore it is challenging to find appropriate therapeutic targets...
June 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28624473/antibody-blood-brain-barrier-efflux-is-modulated-by-glycan-modification
#5
John M Finke, Kari R Ayres, Ryan P Brisbin, Hali A Hill, Emily E Wing, William A Banks
BACKGROUND: Drug delivery to the brain is a major roadblock to treatment of Alzheimer's disease. Recent results of the PRIME study indicate that increasing brain penetration of antibody drugs improves Alzheimer's treatment outcomes. New approaches are needed to better accomplish this goal. Based on prior evidence, the hypothesis that glycan modification alters antibody blood-brain barrier permeability was tested here. METHODS: The blood-brain barrier permeability coefficient Pe of different glycosylated states of anti-amyloid IgG was measured using in vitro models of brain microvascular endothelial cells...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28617696/should-hyperoxia-be-avoided-during-sepsis-an-experimental-study-in-ovine-peritonitis
#6
Xinrong He, Fuhong Su, Keliang Xie, Fabio Silvio Taccone, Katia Donadello, Jean-Louis Vincent
OBJECTIVES: Optimizing oxygen delivery is an important part of the hemodynamic resuscitation of septic shock, but concerns have been raised over the potentially deleterious effects of hyperoxia. We evaluated the impact of hyperoxia on hemodynamics, the microcirculation, and cerebral and renal metabolism in an ovine model of septic shock. DESIGN: Randomized animal study. SETTING: University hospital animal research laboratory. SUBJECTS: Fourteen adult female sheep...
June 14, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28608454/accelerated-atherosclerosis-in-anca-associated-vasculitis
#7
I González-Suárez, J J Ríos-Blanco, J Arpa
OBJECTIVES: Cardiovascular disease, including myocardial infarction and stroke, is a major cause of mortality in ANCA-associated vasculitis (AAV). Although AAV affects small vessels, an accelerated atherosclerosis not explained by traditional cardiovascular risk factors (CVRF) has been demonstrated. We aimed to investigate the association of atherosclerosis measured by carotid intima-media thickness (CIMT) and cerebral small vessel disease in AAV-patients. MATERIALS & METHODS: Twenty-three AAV-patients in complete remission were recruited...
June 12, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28604116/the-cognitive-decline-in-older-patients-with-end-stage-renal-disease-cope-study-rationale-and-design
#8
Noeleen Berkhout-Byrne, Marije H Kallenberg, André Gaasbeek, Ton J Rabelink, Sebastiaan Hammer, Mark A van Buchem, Matthias J van Osch, Lucia J M Kroft, Henk Boom, Simon P Mooijaart, Marjolijn van Buren
BACKGROUND: Older patients with end stage renal disease (ESRD) are at increased risk for cognitive decline, but detailed studies of the magnitude of cognitive decline on dialysis or comprehensive conservative management (CCM) are lacking and the underlying pathophysiological mechanisms have poorly been studied. OBJECTIVE: To describe the rationale and design of the COPE study. Study objectives are firstly to examine the severity of cognitive impairment in older patients reaching ESRD before dialysis and the rate of decline after dialysis or CCM initiation...
June 10, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28580182/cerebral-microvascular-accumulation-of-tau-oligomers-in-alzheimer-s-disease-and-related-tauopathies
#9
Diana L Castillo-Carranza, Ashley N Nilson, Candice E Van Skike, Jordan B Jahrling, Kishan Patel, Prajesh Garach, Julia E Gerson, Urmi Sengupta, Jose Abisambra, Peter Nelson, Juan Troncoso, Zoltan Ungvari, Veronica Galvan, Rakez Kayed
The importance of vascular contributions to cognitive impairment and dementia (VCID) associated with Alzheimer's disease (AD) and related neurodegenerative diseases is increasingly recognized, however, the underlying mechanisms remain obscure. There is growing evidence that in addition to Aβ deposition, accumulation of hyperphosphorylated oligomeric tau contributes significantly to AD etiology. Tau oligomers are toxic and it has been suggested that they propagate in a "prion-like" fashion, inducing endogenous tau misfolding in cells...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28570028/transthyretin-stability-is-critical-in-assisting-beta-amyloid-clearance-relevance-of-transthyretin-stabilization-in-alzheimer-s-disease
#10
Mobina Alemi, Sara C Silva, Isabel Santana, Isabel Cardoso
BACKGROUND: The absence of transthyretin (TTR) in AD mice decreases brain Aβ clearance and reduces the low-density lipoprotein receptor-related protein 1 (LRP1). It is possible that neuroprotection by TTR is dependent on its tetramer structural stability, as studies using TTR mutants showed that unstable L55P TTR has low affinity for Aβ, and TTR tetrameric stabilizers such as iododiflunisal ameliorate AD features in vivo. METHODS: We firstly investigated TTR folding status in human plasma measuring the resistance to urea denaturation...
July 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28559496/magnetic-resonance-imaging-of-cardiovascular-function-and-the-brain-is-dementia-a-cardiovascular-driven-disease
#11
REVIEW
Albert de Roos, Jeroen van der Grond, Gary Mitchell, Jos Westenberg
The proximal aorta acts as a coupling device between heart and brain perfusion, modulating the amount of pressure and flow pulsatility transmitted into the cerebral microcirculation. Stiffening of the proximal aorta is strongly associated with age and hypertension. The detrimental effects of aortic stiffening may result in brain damage as well as heart failure. The resulting cerebral small vessel disease and heart failure may contribute to early cognitive decline and (vascular) dementia. This pathophysiological sequence of events underscores the role of cardiovascular disease as a contributory mechanism in causing cognitive decline and dementia and potentially may provide a starting point for prevention and treatment...
May 30, 2017: Circulation
https://www.readbyqxmd.com/read/28555373/blood-brain-barrier-injury-in-diabetes-unrecognized-effects-on-brain-and-cognition
#12
REVIEW
Marina Bogush, Nathan A Heldt, Yuri Persidsky
Diabetes mellitus (DM) is a disorder due to the inability properly to metabolize glucose associated with dysregulation of metabolic pathways of lipids and proteins resulting in structural and functional changes of various organ systems. DM has detrimental effects on the vasculature, resulting in the development of various cardiovascular diseases and stemming from microvascular injury. The blood brain barrier (BBB) is a highly specialized structure protecting the unique microenvironment of the brain. Endothelial cells, connected by junctional complexes and expressing numerous transporters, constitute the main cell type in the BBB...
May 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28549973/targeted-delivery-of-rosmarinic-acid-across-the-blood-brain-barrier-for-neuronal-rescue-using-polyacrylamide-chitosan-poly-lactide-co-glycolide-nanoparticles-with-surface-cross-reacting-material-197-and-apolipoprotein-e
#13
Yung-Chih Kuo, Rajendiran Rajesh
Rosmarinic acid-loaded polyacrylamide-chitosan-poly(lactide-co-glycolide) nanoparticles (RA-PAAM-CH-PLGA NPs) were grafted with cross-reacting material 197 (CRM197) and apolipoprotein E (ApoE) for targeting of the blood-brain barrier (BBB) and rescuing degenerated neurons. The polymeric nanocarriers were prepared by microemulsion, solvent diffusion, grafting, and surface modification, and CRM197-ApoE-RA-PAAM-CH-PLGA NPs were used to treat human brain-microvascular endothelial cells, RWA264.7 cells, and Aβ-insulted SK-N-MC cells...
May 24, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28540180/hemoglobin-and-mean-platelet-volume-predicts-diffuse-t1-mri-white-matter-volume-decrease-in-sickle-cell-disease-patients
#14
Soyoung Choi, Adam M Bush, Matthew T Borzage, Anand A Joshi, William J Mack, Thomas D Coates, Richard M Leahy, John C Wood
Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28534661/characterization-of-human-fetal-brain-endothelial-cells-reveals-barrier-properties-suitable-for-in%C3%A2-vitro-modeling-of-the-bbb-with-syngenic-co-cultures
#15
Allison M Andrews, Evan M Lutton, Lee A Cannella, Nancy Reichenbach, Roshanak Razmpour, Matthew J Seasock, Steven J Kaspin, Steven F Merkel, Dianne Langford, Yuri Persidsky, Servio H Ramirez
Endothelial cells (ECs) form the basis of the blood-brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#16
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
#17
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
#18
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
#19
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
#20
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
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