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Microvascular disease of the brain

Yijun Pan, Jennifer L Short, Stephanie A Newman, Kwok H C Choy, Durgesh Tiwari, Christopher Yap, Danielle Senyschyn, William A Banks, Joseph A Nicolazzo
Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain β-amyloid (Aβ) levels, and the brain clearance of Aβ is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Aβ. The brain clearance of intracerebroventricularly (icv) administered125 I-Aβ42 was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300 mg/kg for 21 days)...
March 12, 2018: Brain, Behavior, and Immunity
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Hiroya Kuwahara, Jindong Song, Takahiro Shimoura, Kie Yoshida-Tanaka, Tadahaya Mizuno, Tatsuki Mochizuki, Satoshi Zeniya, Fuying Li, Kazutaka Nishina, Tetsuya Nagata, Shingo Ito, Hiroyuki Kusuhara, Takanori Yokota
The blood-brain barrier (BBB) is increasingly regarded as a dynamic interface that adapts to the needs of the brain, responds to physiological changes, and gets affected by and can even promote diseases. Modulation of BBB function at the molecular level in vivo is beneficial for a variety of basic and clinical studies. Here we show that our heteroduplex oligonucleotide (HDO), composed of an antisense oligonucleotide and its complementary RNA, conjugated to α-tocopherol as a delivery ligand, efficiently reduced the expression of organic anion transporter 3 (OAT3) gene in brain microvascular endothelial cells in mice...
March 12, 2018: Scientific Reports
Tatyana Merkulova-Rainon, Chris S Mantsounga, Dong Broquères-You, Cristina Pinto, José Vilar, Diana Cifuentes, Philippe Bonnin, Nathalie Kubis, Daniel Henrion, Jean-Sébastien Silvestre, Bernard I Lévy
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0...
March 7, 2018: Angiogenesis
Cinzia Antognelli, Eliana Trapani, Simona Delle Monache, Andrea Perrelli, Claudia Fornelli, Francesca Retta, Paola Cassoni, Vincenzo Nicola Talesa, Saverio Francesco Retta
This article contains additional data related to the original research article entitled "KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: implication for Cerebral Cavernous Malformation disease" (Antognelli et al., 2017) [1]. Data were obtained by si-RNA-mediated gene silencing, qRT-PCR, immunoblotting, and immunohistochemistry studies, and enzymatic activity and apoptosis assays. Overall, they support, complement and extend original findings demonstrating that KRIT1 loss-of-function induces a redox-sensitive and JNK-dependent sustained upregulation of the master Nrf2 antioxidant defense pathway and its downstream target Glyoxalase 1 (Glo1), and a drop in intracellular levels of AP-modified Hsp70 and Hsp27 proteins, leading to a chronic adaptive redox homeostasis that sensitizes cells to oxidative DNA damage and apoptosis...
February 2018: Data in Brief
Takakuni Maki, Anna Morancho, Pablo Martinez-San Segundo, Kazuhide Hayakawa, Hajime Takase, Anna C Liang, Marina Gabriel-Salazar, Esperanza Medina-Gutiérrez, Kazuo Washida, Joan Montaner, Josephine Lok, Eng H Lo, Ken Arai, Anna Rosell
BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion. METHODS: The secretome of mouse EPCs was analyzed with a proteome array...
March 6, 2018: Stroke; a Journal of Cerebral Circulation
Vigdis Andersen Eidsvaag, Hans-Arne Hansson, Kjell Heuser, Erlend A Nagelhus, Per Kristian Eide
AIM: Idiopathic intracranial hypertension (IIH) is characterized by symptoms indicative of increased intracranial pressure (ICP), such as headache and visual impairment. We have previously reported that brain biopsies from IIH patients show patchy astrogliosis and increased expression of the water channel aquaporin-4 (AQP4) at perivascular astrocytic endfeet. METHODS: The present study was undertaken to investigate for ultrastructural changes of the cerebral capillaries in individuals with IIH...
February 22, 2018: Brain Research
A Abdelhak, A Hübers, K Böhm, A C Ludolph, J Kassubek, E H Pinkhardt
BACKGROUND: Changes in skin and muscle small blood vessels (SBVs) and microvascular structures of the brain have been reported in patients with amyotrophic lateral sclerosis (ALS). A direct assessment of brain SBVs in vivo is currently not feasible. Retinal vessels are considered a "mirror" of brain SBVs. In this study, we used optic coherence tomography (OCT)-based measurements to detect changes in retinal blood vessels of ALS patients compared to those of healthy controls...
February 20, 2018: Journal of Neurology
Xiang Zou, Zehan Wu, Jun Huang, Peixi Liu, Xuanfeng Qin, Liang Chen, Wei Zhu, Yao Zhao, Peiliang Li, Jianping Song, Guo-Yuan Yang, Ying Mao
BACKGROUND: The molecular mechanism of brain arteriovenous malformation (BAVM) is largely unknown. Intracranial venous hypertension (VH) may enhance focal angiogenesis and promote BAVM development and progression. A rat VH model effectively simulates the hemodynamic microenvironment of this disease. OBJECTIVE: To explore the effect of doxycycline in VH-related angiogenesis, as well as the role of matrix metalloproteinase-3 (MMP-3) and other molecular factors. METHODS: A rat VH model was generated by common carotid artery and distal external jugular vein anastomosis...
February 16, 2018: Neurosurgery
Jun Hua, Peiying Liu, Tae Kim, Manus Donahue, Swati Rane, J Jean Chen, Qin Qin, Seong-Gi Kim
The measurement of cerebral blood volume (CBV) has been the topic of numerous neuroimaging studies. To date, however, most in vivo imaging approaches can only measure CBV summed over all types of blood vessels, including arterial, capillary and venous vessels in the microvasculature (i.e. total CBV or CBVtot). As different types of blood vessels have intrinsically different anatomy, function and physiology, the ability to quantify CBV in different segments of the microvascular tree may furnish information that is not obtainable from CBVtot, and may provide a more sensitive and specific measure for the underlying physiology...
February 16, 2018: NeuroImage
Nathalie Thorin-Trescases, Olivia de Montgolfier, Anthony Pinçon, Adeline Raignault, Laurie Caland, Pauline Labbé, Eric Thorin
Aging is a modern concept: human life expectancy has more than doubled in less than 150 years in Western countries. Longer lifespan, however, reveals age-related diseases, including cerebrovascular diseases. The vascular system is a prime target of aging: the "wear and tear" of large elastic arteries exposed to a life-long pulsatile pressure causes arterial stiffening by fragmentation of elastin fibers and replacement by stiffer collagen. This arterial stiffening increases in return the amplitude of the pulse pressure (PP), its wave penetrating deeper into the microcirculation of low resistance, high flow organs such as the brain...
February 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Isobel Parkes, Satyan Chintawar, M Zameel Cader
From the earliest stages of development, when cerebral angiogenesis and neurogenesis are entwined, to the end of life, the interplay between vascular and neural systems of the brain is critical in health and disease. Cerebral microvascular endothelial cells constitute the blood-brain barrier and in concert with pericytes or smooth muscle cells, glia and neurons, integrate into a functional neurovascular unit (NVU). This multicellular NVU maintains homoeostasis of the brain's microenvironment by restricting the entry of systemic pathogens and neurotoxins as well as meeting the metabolic demands of neural activity...
February 14, 2018: Clinical Science (1979-)
Yang Shen, Bin Cao, Noah R Snyder, Kevin M Woeppel, James R Eles, Xinyan Tracy Cui
BACKGROUND: Oxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactive oxygen species (ROS) or reactive nitrogen species generation in the central nervous system (CNS), but the delivery of RSV into the brain through systemic administration is inefficient. Here, we have developed a RSV delivery vehicle based on polylactic acid (PLA)-coated mesoporous silica nanoparticles (MSNPs), conjugated with a ligand peptide of low-density lipoprotein receptor (LDLR) to enhance their transcytosis across the blood-brain barrier (BBB)...
February 13, 2018: Journal of Nanobiotechnology
B K Al-Khazraji, C T Appleton, F Beier, T B Birmingham, J K Shoemaker
OBJECTIVE: Population-based cohort studies suggest an association between osteoarthritis (OA) and cerebrovascular disease, yet the mechanisms underlying vascular comorbidities in OA remain unclear. The purpose of this narrative review is to discuss the literature examining inflammation in OA with a focus on physiological mechanisms, and whether overlapping mechanisms exist in cerebrovascular dysfunction. METHOD: A literature search was conducted in PubMed using combinations of search terms: osteoarthritis, cerebrovascular (disease/dysfunction/risk), cardiovascular (disease/dysfunction/risk), aging/ageing, inflammation, inflammatory mediators, cytokine, c-reactive protein, interleukin, advanced glycation end-products, metabolic syndrome, reactive oxidative species, cognitive impairment, (vascular-related) dementia, small cerebral vessel disease, endothelial function, blood-brain barrier, gender/sex, hypertension, peripheral vascular health, and physical activity...
January 31, 2018: Osteoarthritis and Cartilage
Mark Fisher, Kevin Kapur, Sylvia Soo, Yung Lyou, Steven S Schreiber, Michael J Kim
Disseminated microinfarctions are uncommonly encountered in clinical practice. Here we describe a patient with long-standing cerebral microbleeds who developed acute cognitive decline in the setting of acute hypotension. Magnetic resonance imaging showed acute disseminated microinfarctions, with no change in microbleeds. This case emphasizes the important relationship between ischemic and hemorrhagic microvascular disease of the brain, especially in the setting of acute blood pressure changes compounding preexisting microvascular injury...
January 25, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Dana R Jorgensen, C Elizabeth Shaaban, Clayton A Wiley, Peter J Gianaros, Joseph Mettenburg, Caterina Rosano
Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent, but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon...
February 2, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Harry V Vinters, Chris Zarow, Ewa Borys, Jeffrey D Whitman, Spencer Tung, William G Ellis, Ling Zheng, Helena C Chui
The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the 'aging brain'. These include angiopathies (affecting both large and small arteries) that result from 'classical' risk factors (hypertension, smoking, diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD-though the vascular abnormalities are usually detectable by neuroimaging...
January 30, 2018: Neuropathology and Applied Neurobiology
Slava Rom, Viviana Zuluaga-Ramirez, Nancy L Reichenbach, Michelle A Erickson, Malika Winfield, Sachin Gajghate, Melpo Christofidou-Solomidou, Kelly L Jordan-Sciutto, Yuri Persidsky
BACKGROUND: Secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, is known for its beneficial effects in inflammation, oxidative stress, heart disease, tumor progression, atherosclerosis, and diabetes. SDG might be an attractive natural compound that protects against neuroinflammation. Yet, there are no comprehensive studies to date investigating the effects of SDG on brain endothelium using relevant in vivo and in vitro models. METHODS: We evaluated the effects of orally administered SDG on neuroinflammatory responses using in vivo imaging of the brain microvasculature during systemic inflammation and aseptic encephalitis...
January 27, 2018: Journal of Neuroinflammation
Marios K Georgakis, Despoina Chatzopoulou, Georgios Tsivgoulis, Eleni Th Petridou
OBJECTIVES: To determine whether albuminuria, a marker of systemic endothelial dysfunction, is associated with cerebral small vessel disease (SVD). DESIGN: Systematic review following the Meta-analyses Of Observational Studies in Epidemiology guidelines; independent reviewers searched Pubmed/Medline and Scopus, data were extracted, studies were evaluated on quality, and random-effects models were implemented for meta-analysis. SETTING: Observational studies quantifying an association between albuminuria and cerebral SVD...
January 25, 2018: Journal of the American Geriatrics Society
Julia B M Zeller, Andrea Katzorke, Laura D Müller, Judith Breunig, Florian B Haeussinger, Jürgen Deckert, Bodo Warrings, Martin Lauer, Thomas Polak, Martin J Herrmann
Spontaneous low frequency oscillations (LFO) in functional imaging data have gained increased interest in the study of cognitive decline. Persons diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display alterations in their amount of LFO in various brain regions. This is commonly interpreted as disruptions in the autoregulation of the cerebral microvascular system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54 MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during rest over the frontal and the parietal cortex...
January 23, 2018: Brain Imaging and Behavior
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