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Microvascular disease of the brain

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https://www.readbyqxmd.com/read/28890893/proximate-mediators-of-microvascular-dysfunction-at-the-blood-brain-barrier-neuroinflammatory-pathways-to-neurodegeneration
#1
REVIEW
Barry W Festoff, Ravi K Sajja, Luca Cucullo
Current projections are that by 2050 the numbers of people aged 65 and older with Alzheimer's disease (AD) in the US may increase threefold while dementia is projected to double every 20 years reaching ~115 million by 2050. AD is clinically characterized by progressive dementia and neuropathologically by neuronal and synapse loss, accumulation of amyloid plaques, and neurofibrillary tangles (NFTs) in specific brain regions. The preclinical or presymptomatic stage of AD-related brain changes may begin over 20 years before symptoms occur, making development of noninvasive biomarkers essential...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28886695/cerebral-microvascular-dysfunction-in-metabolic-syndrome-is-exacerbated-by-ischemia-reperfusion-injury
#2
Nathalie Obadia, Marcos Adriano Lessa, Anissa Daliry, Raquel Rangel Silvares, Fabiana Gomes, Eduardo Tibiriçá, Vanessa Estato
BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS. RESULTS: We examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery...
September 8, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28853030/hypertension-impairs-neurovascular-coupling-and-promotes-microvascular-injury-role-in-exacerbation-of-alzheimer-s-disease
#3
Anna Csiszar, Stefano Tarantini, Gábor A Fülöp, Tamas Kiss, M Noa Valcarcel-Ares, Veronica Galvan, Zoltan Ungvari, Andriy Yabluchanskiy
Hypertension in the elderly substantially increases both the risk of vascular cognitive impairment (VCI) and Alzheimer's disease (AD); however, the underlying mechanisms are not completely understood. This review discusses the effects of hypertension on structural and functional integrity of cerebral microcirculation, including hypertension-induced alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage (capillary rarefaction, blood-brain barrier disruption), and the genesis of cerebral microhemorrhages and their potential role in exacerbation of cognitive decline associated with AD...
August 29, 2017: GeroScience
https://www.readbyqxmd.com/read/28800332/cerebral-oxidative-stress-and-microvasculature-defects-in-tnf-%C3%AE-expressing-transgenic-and-porphyromonas-gingivalis-infected-apoe-mice
#4
Farheen Rokad, Ryan Moseley, Rowan S Hardy, Sasanka Chukkapalli, StJohn Crean, Lakshmyya Kesavalu, Sim K Singhrao
The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain. This study examined oxidative stress, in the form of increased protein carbonylation and oxidative protein damage, in the tumor necrosis factor-α (TNF-α) transgenic mouse that models inflammatory TNF-α excess during bacterial infection; and in the apolipoprotein knockout (ApoE-/-) mouse brains, following Porphyromonas gingivalis gingival monoinfection...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28768311/temporal-relation-between-myocardial-fibrosis-and-heart-failure-with-preserved-ejection-fraction-association-with-baseline-disease-severity-and-subsequent-outcome
#5
Erik B Schelbert, Yaron Fridman, Timothy C Wong, Hussein Abu Daya, Kayla M Piehler, Ajay Kadakkal, Christopher A Miller, Martin Ugander, Maren Maanja, Peter Kellman, Dipan J Shah, Kaleab Z Abebe, Marc A Simon, Giovanni Quarta, Michele Senni, Javed Butler, Javier Diez, Margaret M Redfield, Mihai Gheorghiade
Importance: Among myriad changes occurring during the evolution of heart failure with preserved ejection fraction (HFpEF), cardiomyocyte-extracellular matrix interactions from excess collagen may affect microvascular, mechanical, and electrical function. Objective: To investigate whether myocardial fibrosis (MF) is similarly prevalent both in those with HFpEF and those at risk for HFpEF, similarly associating with disease severity and outcomes. Design, Setting, and Participants: Observational cohort study from June 1, 2010, to September 17, 2015, with follow-up until December 14, 2015, at a cardiovascular magnetic resonance (CMR) center serving an integrated health system...
August 2, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28741167/microvascular-ultrastructural-changes-precede-cognitive-impairment-in-the-murine-appswe-ps1de9-model-of-alzheimer-s-disease
#6
Patricia Kelly, Paul Denver, Simon C Satchell, Maximilian Ackermann, Moritz A Konerding, Christopher A Mitchell
Cerebral and systemic organ microvascular pathologies coexist with human Alzheimer's disease (AD) neuropathology. In this study, we hypothesised that both cerebral and systemic microvascular pathologies exist in 4- to 5-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice prior to the onset of cognitive impairment. To assess this we examined recognition memory in both wild-type and APP/PS1 mice using the object recognition task (ORT; n = 11 per group) and counted thioflavin-S-positive plaques in brain (n = 6 per group)...
July 25, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28730529/role-of-the-golgi-apparatus-in-the-blood-brain-barrier-golgi-protection-may-be-a-targeted-therapy-for-neurological-diseases
#7
REVIEW
Shuwen Deng, Hui Liu, Ke Qiu, Hong You, Qiang Lei, Wei Lu
The blood-brain barrier (BBB) protects the brain from toxic material in the blood, provides nutrients for brain tissues, and screens harmful substances from the brain. The specific brain microvascular endothelial cells (BMVECs), tight junction between endothelial cells, and astrocytes ensure proper function of the central nervous system (CNS). Pathological factors disrupt the integrity of the BBB by destroying the normal function of endothelial cells and decreasing the production of tight junction proteins or the expression of proteins specifically localized on astrocytes...
July 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28713881/drug-delivery-and-nanoformulations-for-the-cardiovascular-system
#8
W J Geldenhuys, M T Khayat, J Yun, M A Nayeem
Therapeutic delivery to the cardiovascular system may play an important role in the successful treatment of a variety of disease state, including atherosclerosis, ischemic-reperfusion injury and other types of microvascular diseases including hypertension. In this review we evaluate the different options available for the development of suitable delivery systems that include the delivery of small organic compounds [adenosin A2A receptor agonist (CGS 21680), CYP-epoxygenases inhibitor (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy] benzoic acid), soluble epoxide hydrolase inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide), PPARγ agonist (rosiglitazone) and PPARγ antagonist (T0070907)], nanoparticles, peptides, and siRNA to the cardiovascular system...
February 2017: Res Rev Drug Deliv
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#9
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28699046/optical-clearing-and-fluorescence-deep-tissue-imaging-for-3d-quantitative-analysis-of-the-brain-tumor-microenvironment
#10
Tonny Lagerweij, Sophie A Dusoswa, Adrian Negrean, Esther M L Hendrikx, Helga E de Vries, Jeroen Kole, Juan J Garcia-Vallejo, Huibert D Mansvelder, W Peter Vandertop, David P Noske, Bakhos A Tannous, René J P Musters, Yvette van Kooyk, Pieter Wesseling, Xi Wen Zhao, Thomas Wurdinger
BACKGROUND: Three-dimensional visualization of the brain vasculature and its interactions with surrounding cells may shed light on diseases where aberrant microvascular organization is involved, including glioblastoma (GBM). Intravital confocal imaging allows 3D visualization of microvascular structures and migration of cells in the brain of mice, however, with limited imaging depth. To enable comprehensive analysis of GBM and the brain microenvironment, in-depth 3D imaging methods are needed...
July 11, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28698560/all-muscarinic-acetylcholine-receptors-m1-m5-are-expressed-in-murine-brain-microvascular-endothelium
#11
Beatrice Mihaela Radu, Antonio Marco Maria Osculati, Eda Suku, Adela Banciu, Grygoriy Tsenov, Flavia Merigo, Marzia Di Chio, Daniel Dumitru Banciu, Cristina Tognoli, Petr Kacer, Alejandro Giorgetti, Mihai Radu, Giuseppe Bertini, Paolo Francesco Fabene
Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697558/comparative-analysis-of-cortical-microinfarcts-and-microbleeds-using-3-0-tesla-postmortem-magnetic-resonance-images-and-histopathology
#12
Atsushi Niwa, Yuichiro Ii, Akihiro Shindo, Ko Matsuo, Hidehiro Ishikawa, Akira Taniguchi, Shinichi Takase, Masayuki Maeda, Hajime Sakuma, Hiroyasu Akatsu, Yoshio Hashizume, Hidekazu Tomimoto
Microvascular lesions including cortical microinfarctions (CMIs) and cerebral lobar microbleeds (CMBs) are usually caused by cerebral amyloid angiopathy (CAA) in the elderly and are correlated with cognitive decline. However, their radiological-histopathological coincidence has not been revealed systematically with widely used 3-Tesla (3T) magnetic resonance imaging (MRI). The purpose of the present study is to delineate the histopathological background corresponding to MR images of these lesions. We examined formalin-fixed 10-mm thick coronal brain blocks from 10 CAA patients (five were also diagnosed with Alzheimer's disease, three with dementia with Lewy bodies, and two with CAA only) with dementia and six non CAA patients with neurodegenerative disease...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28696548/brain-microvascular-injury-and-white-matter-disease-provoked-by-diabetes-associated-hyperamylinemia
#13
Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E Saatman, Peter T Nelson, John T Slevin, Larry B Goldstein, Geert Jan Biessels, Florin Despa
OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins. METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping...
August 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28692445/normal-cerebral-vascular-pulsations-in-humans-changes-with-age-and-implications-for-microvascular-disease
#14
Mi O Kim, Yan Li, Fangfei Wei, Jiguang Wang, Michael F O'Rourke, Audrey Adji, Alberto P Avolio
BACKGROUND: Cerebral syndromes in older humans, secondary stroke in younger persons following trauma, and sickle cell anaemia in children, are linked by unexplained microvascular damage and high cerebral pressure or flow pulsations. The aim of this study was to characterize age-related pressure and flow waveforms patterns entering the brain, to explain these in terms of disturbed physiological function, and to consider clinical implications. METHOD: Blood flow velocity waves were measured in four cerebral vascular territories by transcranial Doppler of 1020 apparently normal patients (497 men, 21-78 years)...
July 7, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28687674/anti-inflammatory-%C3%AF-3-endocannabinoid-epoxides
#15
Daniel R McDougle, Josephine E Watson, Amr A Abdeen, Reheman Adili, Megan P Caputo, John E Krapf, Rodney W Johnson, Kristopher A Kilian, Michael Holinstat, Aditi Das
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report on the endogenous production of a previously unknown class of ω-3 PUFA-derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP) epoxygenase metabolic pathways. The ω-3 endocannabinoid epoxides are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28685422/chronic-diseases-as-barriers-to-oxygen-delivery-a-unifying-hypothesis-of-tissue-reoxygenation-therapy
#16
G A Perdrizet
Modern medical practice has resulted in the accumulation of a growing number of incurable chronic diseases, many of which are inflammatory in nature. Inflammation establishes a hypoxic microenvironment within tissues, a condition of inflammatory hypoxia (IH). Tissues thus affected become severely compromised, are unable to elicit adaptive responses and eventually develop fibrosis and fixed microvascular deficits. Previous work has demonstrated that tissue hypoxia exits even within the simple human model of self-resolving inflammation, the tuberculin reaction...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28679661/glucose-regulated-protein-78-autoantibody-associates-with-blood-brain-barrier-disruption-in-neuromyelitis-optica
#17
Fumitaka Shimizu, Kristin L Schaller, Gregory P Owens, Anne C Cotleur, Debra Kellner, Yukio Takeshita, Birgit Obermeier, Thomas J Kryzer, Yasuteru Sano, Takashi Kanda, Vanda A Lennon, Richard M Ransohoff, Jeffrey L Bennett
Neuromyelitis optica (NMO) is an inflammatory disorder mediated by antibodies to aquaporin-4 (AQP4) with prominent blood-brain barrier (BBB) breakdown in the acute phase of the disease. Anti-AQP4 antibodies are produced mainly in the periphery, yet they target the astrocyte perivascular end feet behind the BBB. We reasoned that an endothelial cell-targeted autoantibody might promote BBB transit of AQP4 antibodies and facilitate NMO attacks. Using monoclonal recombinant antibodies (rAbs) from patients with NMO, we identified two that strongly bound to the brain microvascular endothelial cells (BMECs)...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28674030/s-nitrosoglutathione-reductase-deficiency-confers-improved-survival-and-neurological-outcome-in-experimental-cerebral-malaria
#18
Robyn E Elphinstone, Rickvinder Besla, Eric A Shikatani, Ziyue Lu, Alfred Hausladen, Matthew Davies, Clinton S Robbins, Mansoor Husain, Jonathan S Stamler, Kevin C Kain
Artesunate remains the mainstay of treatment for cerebral malaria, but it is less effective in later stages of disease when the host inflammatory response and blood-brain barrier integrity dictate clinical outcomes. Nitric oxide (NO) is an important regulator of inflammation and microvascular integrity, and impaired NO bioactivity is associated with fatal outcomes in malaria. Endogenous NO bioactivity in mammals is largely mediated by S-nitrosothiols (SNOs). Based on these observations, we hypothesized that animals deficient in the SNO-metabolizing enzyme, S-nitrosoglutathione reductase (GSNOR), which exhibit enhanced S-nitrosylation, would have improved outcomes in a preclinical model of cerebral malaria...
September 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28666911/geometrical-complexity-of-cortical-microvascularization-in-moyamoya-disease
#19
Katsuya Komatsu, Takeshi Mikami, Hime Suzuki, Yukinori Akiyama, Rei Enatsu, Masahiko Wanibuchi, Nobuhiro Mikuni
BACKGROUND: Dilatation of the microvascular diameter is recognized in moyamoya disease, and referred to as microvascularization. The purpose of this study is to characterize the cortical microvascularization in moyamoya disease using imaging analysis, and to discuss the developmental mechanism of the collateral network around the cortical surface. METHODS: A total of 20 hemispheric sides of 14 patients with moyamoya disease were included in this study. From the intraoperative images, cortical surface images were extracted, and binary images were subsequently created...
June 27, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28664509/hypertension-induced-synapse-loss-and-impairment-in-synaptic-plasticity-in-the-mouse-hippocampus-mimics-the-aging-phenotype-implications-for-the-pathogenesis-of-vascular-cognitive-impairment
#20
Zsuzsanna Tucsek, M Noa Valcarcel-Ares, Stefano Tarantini, Andriy Yabluchanskiy, Gábor Fülöp, Tripti Gautam, Albert Orock, Anna Csiszar, Ferenc Deak, Zoltan Ungvari
Strong epidemiological and experimental evidence indicates that hypertension has detrimental effects on the cerebral microcirculation and thereby promotes accelerated brain aging. Hypertension is an independent risk factor for both vascular cognitive impairment (VCI) and Alzheimer's disease (AD). However, the pathophysiological link between hypertension-induced cerebromicrovascular injury (e.g., blood-brain barrier disruption, increased microvascular oxidative stress, and inflammation) and cognitive decline remains elusive...
June 29, 2017: GeroScience
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