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Microvascular disease of the brain

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https://www.readbyqxmd.com/read/28236166/alteration-of-regional-homogeneity-and-white-matter-hyperintensities-in-amnestic-mild-cognitive-impairment-subtypes-are-related-to-cognition-and-csf-biomarkers
#1
Xiao Luo, Yerfan Jiaerken, Peiyu Huang, Xiao Jun Xu, Tiantian Qiu, Yunlu Jia, Zhujing Shen, Xiaojun Guan, Jiong Zhou, Minming Zhang
Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified...
February 24, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#2
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28199219/clinical-applications-of-near-infrared-diffuse-correlation-spectroscopy-and-tomography-for-tissue-blood-flow-monitoring-and-imaging
#3
Yu Shang, Ting Li, Guoqiang Yu
Near-infrared (NIR) light enables the deep tissue investigation of microvascular hemodynamics. Blood flow is one such available observable promoting a wealth of physiological insight both individually and in combination with other metrics. Diffuse correlation spectroscopy (DCS) and, to a lesser extent, diffuse correlation tomography (DCT), have received interest over the past two decades as noninvasive methods for tissue blood flow measurement and imaging. DCS employs coherent point-illumination NIR light to penetrate deep tissues and commonly uses avalanche photodiodes to detect temporal speckle fluctuations of the diffuse light in a single speckle area of tissue surface, which are sensitive to the motions of red blood cells in the microvasculature of the detected tissue volume...
February 15, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28195555/blood-brain-barrier-supported-neurogenesis-in-healthy-and-diseased-brain
#4
Elena A Pozhilenkova, Olga L Lopatina, Yulia K Komleva, Vladimir V Salmin, Alla B Salmina
Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis...
February 14, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28178960/ultrasound-and-dynamic-functional-imaging-in-vascular-cognitive-impairment-and-alzheimer-s-disease
#5
REVIEW
Branko Malojcic, Panteleimon Giannakopoulos, Farzaneh A Sorond, Elsa Azevedo, Marina Diomedi, Janja Pretnar Oblak, Nicola Carraro, Marina Boban, Laszlo Olah, Stephan J Schreiber, Aleksandra Pavlovic, Zsolt Garami, Nantan M Bornstein, Bernhard Rosengarten
BACKGROUND: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders...
February 9, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28164774/tauopathies-focus-on-changes-at-the-neurovascular-unit
#6
Alena Michalicova, William A Banks, Jaroslav Legath, Andrej Kovac
In the past, the blood-brain barrier (BBB) had been characterized mainly as a layer of endothelial cells forming the vessel/capillary wall of the brain. More recently, the BBB is considered to be a part of a highly dynamic and interactive system called the neurovascular unit (NVU), consisting of vascular cells, glial cells, and neurons. The list of central nervous system (CNS) pathologies involving BBB dysfunction is rapidly growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to host of processes resulting in progressive synaptic and neuronal dysfunction and loss...
February 3, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28152169/albuminuria-in-association-with-cognitive-function-and-dementia-a-systematic-review-and-meta-analysis
#7
Marios K Georgakis, Nikolaos G Dimitriou, Maria A Karalexi, Constantinos Mihas, Efthimia G Nasothimiou, Dimitrios Tousoulis, Georgios Tsivgoulis, Eleni Th Petridou
OBJECTIVES: Cerebral microvascular disease is considered to contribute to cognitive dysfunction. We opted to explore whether albuminuria, a marker of systemic microangiopathy, is associated with cognitive impairment, dementia, and cognitive function. DESIGN: Systematic review; independent reviewers screened 2359 articles, derived through the search strategy, for identification of observational studies quantifying an association of albuminuria with the outcomes of interest, abstracted data on study characteristics and results and evaluated studies on quality using the Newcastle-Ottawa scale...
February 2, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28130443/na-h-exchanger-9-regulates-iron-mobilization-at-the-blood-brain-barrier-in-response-to-iron-starvation
#8
Rami Beydoun, Mohamed A Hamood, Daniela M Gomez Zubeita, Kalyan C Kondapalli
Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain-iron status information via paracrine signals from ensheathing astrocytes...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28130053/vascular-protective-effects-of-klf2-on-a%C3%AE-induced-toxicity-implications-for-alzheimer-s-disease
#9
Xuejun Fang, Xiaoli Zhong, Gang Yu, Si Shao, Qidong Yang
Alzheimer's disease (AD) is characterized by excessive amounts of senile plaques and neurofibrillary tangles in the brain, and cerebrovascular pathologies in AD are attracting increasingly more attention. Krüppel-like factor (KLF) 2, a transcription regulator expressed in the mouse embryonic vasculature and involved in the regulation of vascular gene expression, serves as a protective factor in endothelial cells. However, whether KLF2 is involved in neurodegenerative disease, and especially in AD, remains unknown...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#10
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 beta-amyloid (Aβ) and is down-regulated in Alzheimer's disease. Studies suggest that the mood-stabilizing drug lithium exerts a protective effect against Alzheimer's disease. Although 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 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28089903/advances-in-mr-angiography-with-7t-mri-from-microvascular-imaging-to-functional-angiography
#11
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 13, 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
#12
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
#13
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
#14
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...
March 2017: 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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