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Microvascular disease of the brain

Christine Silwedel, Christian P Speer, Axel Haarmann, Markus Fehrholz, Heike Claus, Mathias Buttmann, Kirsten Glaser
BACKGROUND: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.). Although commonly regarded as commensals of the adult urogenital tract, Ureaplasma spp...
May 23, 2018: Journal of Neuroinflammation
Yong Lan, Yongjun Li, Dajun Li, Peng Li, Jiyang Wang, Yongpeng Diao, Guodong Ye, Yangfang Li
Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood‑brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co‑cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co‑localization of PLTs, girders of actin filament (girdin) and phosphorylated (p‑)girdin...
May 17, 2018: International Journal of Molecular Medicine
Peter Karczewski, Petra Hempel, Marion Bimmler
Agonistic autoantibodies (agAAB) for alpha-1 adrenoceptor were found in approx. 50% of patients with Alzheimer's disease. These antibodies activate the receptor and trigger the signal cascades similarly to how natural agonists do. The agAAB bond to the receptor is persistent and prolonged. This results in a non-physiological elevation of intracellular calcium. An animal model has shown that agAAB causes macrovascular and microvascular impairment in the vessels of the brain. Reduction in blood flow and the density of intact vessels was significantly demonstrated...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Satoshi Zeniya, Hiroya Kuwahara, Kaiichi Daizo, Akihiro Watari, Masuo Kondoh, Kie Yoshida-Tanaka, Hidetoshi Kaburagi, Ken Asada, Tetsuya Nagata, Masahiro Nagahama, Kiyohito Yagi, Takanori Yokota
Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system...
May 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xuewu Liu, Yuanyuan Wang, Jiao Liang, Luojun Wang, Na Qin, Ya Zhao, Gang Zhao
BACKGROUND: Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease...
May 2, 2018: BMC Genomics
Xintong Ge, Wenzhu Li, Shan Huang, Zhenyu Yin, Mengchen Yang, Zhenying Han, Zhaoli Han, Fanglian Chen, Haichen Wang, Ping Lei, Jian-Ning Zhang
Our recent papers have reported that increased miR-21-5p in brain following traumatic brain injury (TBI) could improve the neurological outcome through alleviating blood-brain barrier (BBB) damage. miR-21-3p is another mature miRNA derived from pre-miR-21 after Dicer Procession other than miR-21-5p. Its roles in various diseases, such as tumors and myocardial disease aroused great interest for research in recent years. To further explore the function and underlying mechanism of miR-21, especially miR-21-3p in regulating the pathological development of BBB damage after TBI, we designed this research and focused on studying the impact of miR-21-3p on apoptosis and inflammation in brain microvascular endothelial cells (BMVECs), the major cellular component of BBB...
April 26, 2018: Journal of Neurotrauma
Midrelle E Noumbissi, Bianca Galasso, Monique F Stins
The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter...
April 23, 2018: Fluids and Barriers of the CNS
Hernán Mejía-Rentería, Jordi A Matias-Guiu, Francesco Lauri, Miguel Yus, Javier Escaned
Coronary microcirculatory dysfunction is a major cause of myocardial ischemia that influences the outcomes of patients with coronary artery disease. The mechanisms of coronary microcirculatory dysfunction are heterogeneous and may result from a spectrum of biological and cardiovascular risk factors that may affect also the microcirculation of other vital organs. Microcirculatory dysfunction of the brain, known as cerebral small vessel disease, is increasingly being recognized as a cause of cognitive decline and neurodegenerative disorders...
April 20, 2018: Minerva Cardioangiologica
Liwen Deng, Rong Mu, Thomas A Weston, Brady L Spencer, Roxanne Liles, Kelly S Doran
Streptococcus agalactiae (Group B Streptococcus , GBS) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immune-compromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCS)...
April 23, 2018: Infection and Immunity
Simona Mancini, Luca Nardo, Maria Gregori, Inês Ribeiro, Francesco Mantegazza, Cristina Delerue-Matos, Massimo Masserini, Clara Grosso
BACKGROUND: Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2 O2 ) scavenger. PURPOSE: In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Catherine A A Lee, Hannah S Seo, Anibal G Armien, Frank S Bates, Jakub Tolar, Samira M Azarin
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown...
April 4, 2018: Fluids and Barriers of the CNS
Barbora Soukupova Urbanova, Jaroslava Paulasova Schwabova, Hana Magerova, Petr Jansky, Hana Markova, Martin Vyhnalek, Jan Laczo, Jakub Hort, Ales Tomek
BACKGROUND: Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. OBJECTIVE: We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holding maneuver. METHODS: Three groups of subjects (AD in the stage of dementia, MCI, and cognitively normal controls) with detailed neuropsychological testing and low cerebrovascular burden (no history of stroke, no intra- or extracranial artery stenoses, and no severe vascular lesions on brain MRI), underwent a TCCS assessment of peak systolic (PSV), mean flow (MFV), and end diastolic velocities (EDV) and resistance and pulsatility indices (RI, PI) in large intracranial vessels bilaterally...
March 24, 2018: Journal of Alzheimer's Disease: JAD
Pooja Dua, Sinae Kang, Hye-Soo Shin, Soyoun Kim, Dong-Ki Lee
Increased interest and insights gained by researchers on the roles of endothelial cells in the pathophysiology of cancer, inflammatory, and cardiovascular diseases have led to the design of pharmacological interventions aimed at the endothelium lining in the diseased sites. Toward this end, we used established brain microvascular endothelial cell lines mouse (bEND3), human (hCMEC/D3), and Toggle Cell-SELEX to identify a species cross-reactive, endothelial cell-internalizing aptamer R11-3. This 2'F-modified RNA aptamer is specific for endothelial cells as no internalization was seen with cells of nonendothelial origin...
April 2, 2018: Nucleic Acid Therapeutics
Yijun Pan, Elonie R Morris, Martin J Scanlon, Philip J Marriott, Christopher Jh Porter, Joseph A Nicolazzo
The cytoplasmic trafficking of docosahexaenoic acid (DHA), a cognitively-beneficial fatty acid, across the blood-brain barrier (BBB) is governed by fatty acid-binding protein 5 (FABP5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD), which is associated with diminished BBB expression of FABP5. Therefore, upregulating FABP5 expression at the BBB may be a novel approach for enhancing BBB transport of DHA in AD. DHA supplementation has been shown to be beneficial in various mouse models of AD, and therefore, the aim of this study was to determine whether DHA has the potential to upregulate the BBB expression of FABP5, thereby enhancing its own uptake into the brain...
March 27, 2018: Journal of Neurochemistry
Pablo Galeano, María C Leal, Carina C Ferrari, María C Dalmasso, Pamela V Martino Adami, María I Farías, Juan C Casabona, Mariana Puntel, Sonia Do Carmo, Clara Smal, Martín Arán, Eduardo M Castaño, Fernando J Pitossi, A Claudio Cuello, Laura Morelli
The specific roles of Notch in progressive adulthood neurodegenerative disorders have begun to be unraveled in recent years. A number of independent studies have shown significant increases of Notch expression in brains from patients at later stages of sporadic Alzheimer's disease (AD). However, the impact of Notch canonical signaling activation in the pathophysiology of AD is still elusive. To further investigate this issue, 2-month-old wild-type (WT) and hemizygous McGill-R-Thy1-APP rats (Tg(+/-)) were injected in CA1 with lentiviral particles (LVP) expressing the transcriptionally active fragment of Notch, known as Notch Intracellular Domain (NICD), (LVP-NICD), or control lentivirus particles (LVP-C)...
March 26, 2018: Molecular Neurobiology
Tatsuya Osaki, Vivek Sivathanu, Roger D Kamm
Neurovascular coupling plays a key role in the pathogenesis of neurodegenerative disorders including motor neuron disease (MND). In vitro models provide an opportunity to understand the pathogenesis of MND, and offer the potential for drug screening. Here, we describe a new 3D microvascular and neuronal network model in a microfluidic platform to investigate interactions between these two systems. Both 3D networks were established by co-culturing human embryonic stem (ES)-derived MN spheroids and endothelial cells (ECs) in microfluidic devices...
March 26, 2018: Scientific Reports
Samuel Sances, Ritchie Ho, Gad Vatine, Dylan West, Alex Laperle, Amanda Meyer, Marlesa Godoy, Paul S Kay, Berhan Mandefro, Seigo Hatata, Chris Hinojosa, Norman Wen, Dhruv Sareen, Geraldine A Hamilton, Clive N Svendsen
Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates...
March 21, 2018: Stem Cell Reports
Abhik Sen, Jarin Hongpaisan
Vascular endothelial dysfunction is a primary phenotype of aging, and microvascular (MV) lesion is mainly associated with Alzheimer's disease (AD). Here we have studied the correlation of MV wall thickness and CA1 pyramidal neuronal pathology in autopsy-confirmed AD brains. Both hyaline (h-MV) and increased cell number (c-MV) associated MV wall thickening was found in age-matched control (AC) hippocampus without significant change in Aβ level (Braak stages 0-III). AC neurons neighboring the h-MV showed lower levels of oxidative DNA/RNA damage and Aβ precursor protein (APP), while the neurons around c-MV showed higher oxidative DNA/RNA damage with increased APP expression...
March 20, 2018: Free Radical Biology & Medicine
Antonio Lopalco, Annalisa Cutrignelli, Nunzio Denora, Angela Lopedota, Massimo Franco, Valentino Laquintana
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl- sn -glycero-3-phosphoethanolamine- N -[carboxy(poly(ethylene glycol)-2000)]...
March 20, 2018: Nanomaterials
Marco Ellis, Lisa Hwang, Ni-Ka Ford, Konstantin Slavin
BACKGROUND: Full-thickness scalp defects pose a reconstructive problem, especially in the setting of infection, chemotherapy/radiation, and underlying cranial defects. Current options include dermal matrices, skin grafts, and local flaps. Local flaps often fail, requiring subsequent microvascular free flap reconstruction. OBJECTIVE: To describe the visor flap, a novel bipedicled advancement flap design, and its role in reconstruction of scalp defects. METHODS: A retrospective review of 21 adult patients who developed scalp defects reconstructed using the visor flap from 2013 to 2017...
March 14, 2018: Operative Neurosurgery (Hagerstown, Md.)
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