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Neurovascular unit

Kavi Devraj, Sylvaine Guérit, Jakranka Macas, Yvonne Reiss
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function...
February 26, 2018: Journal of Visualized Experiments: JoVE
Christos D Karkos, Georgios Koudounas, Ioakeim T Giagtzidis, Maria-Aphroditi Mitka, Ioannis Pliatsios, Konstantinos O Papazoglou
Popliteal artery injury is a potentially-limb threatening complication of traumatic knee dislocation. We describe two such cases that had been treated in our unit over the last decade. The first one was a 23-year-old woman who injured her right knee during a long jump competition and the second was a 27-year-old man who had a motorbike accident. Both suffered traumatic knee dislocation along with significant ligament and neurovascular injuries. In the first patient, the popliteal artery was found thrombosed due to intimal rupture and required thrombectomy and vein patch repair, whereas, in the second patient, the artery was completely transected and required end-to-end anastomosis...
March 5, 2018: Annals of Vascular Surgery
Robert Carlsson, Ilknur Özen, Marco Barbariga, Abderahim Gaceb, Michaela Roth, Gesine Paul
Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation...
2018: PloS One
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
Berta Anuncibay-Soto, Diego Pérez-Rodriguez, María Santos-Galdiano, Enrique Font-Belmonte, Irene F Ugidos, Paloma Gonzalez-Rodriguez, Marta Regueiro-Purriños, Arsenio Fernández-López
BACKGROUND: Blood reperfusion of the ischemic tissue after stroke promotes increases in the inflammatory response as well as accumulation of unfolded/misfolded proteins in the cell, leading to endoplasmic reticulum (ER) stress. Both Inflammation and ER stress are critical processes in the delayed death of the cells damaged after ischemia. The aim of this study is to check the putative synergic neuroprotective effect by combining anti-inflammatory and anti-ER stress agents after ischemia...
February 27, 2018: Biochemical Pharmacology
William Renthal
Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets...
January 1, 2018: Cephalalgia: An International Journal of Headache
Ellaine Salvador, Malgorzata Burek, Carola Y Förster
Traumatic brain injury (TBI) is a significant problem causing high mortality globally. Methods to increase possibilities for treatment and prevention of secondary injuries resulting from the initial physical insult are thus much needed. TBI affects the central nervous system (CNS) and the neurovascular unit as a whole in numerous ways but one of the primarily compromised components is the blood-brain barrier (BBB).In this chapter, we present a detailed procedure on how stretch injury and oxygen-glucose deprivation (OGD) are applied to brain microvascular endothelial cells of the BBB in order to replicate the actual impact they receive during TBI...
2018: Methods in Molecular Biology
Dominik Michalski, Anna L Keck, Jens Grosche, Henrik Martens, Wolfgang Härtig
Because stroke therapies are still limited and patients are often concerned by long-term sequelae with significant impairment of daily living, elaborated neuroprotective strategies are needed. During the last decades, research substantially improved the knowledge on cellular pathologies responsible for stroke-related tissue damage. In this context, the neurovascular unit (NVU) concept has been established, summarizing the affections of neurons, associated astrocytes and the vasculature. Although oligodendrocytes were already identified to play a major role in other brain pathologies, their role during stroke evolution and long-lasting tissue damage is poorly understood...
2018: Frontiers in Cellular Neuroscience
Joshua B Holt, Natalie A Glass, Apurva S Shah
BACKGROUND: Supracondylar humeral fractures (SCHF) are the most common elbow fractures in children. The epidemiology of these injuries in the United States is described. METHODS: The Nationwide Emergency Department Sample database was queried for all children (age, below 18 y) with SCHF treated in the emergency department (ED) from 2006 to 2011, and weighted estimates were extracted. RESULTS: A total of 63,348 ED visits for SCHF were identified...
February 16, 2018: Journal of Pediatric Orthopedics
Yi-Chao Lee, Ying-Chao Chang, Chia-Ching Wu, Chao-Ching Huang
Therapy targeting the neurovascular unit may provide effective neuroprotection against neonatal hypoxia-ischemia (HI). We hypothesized that the peripheral injection of hypoxia-preconditioned human umbilical vein endothelial cells (HUVECs) following HI protects against neurovascular damage and provides long-term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in vitro and had augmented migration effects into the brain when administered intraperitoneally in vivo after HI...
February 19, 2018: Molecular Neurobiology
Maryam Anzabi, Maryam Ardalan, Nina K Iversen, Ali H Rafati, Brian Hansen, Leif Østergaard
Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes...
2018: Frontiers in Cellular Neuroscience
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-)
N Joan Abbott, Michelle E Pizzo, Jane E Preston, Damir Janigro, Robert G Thorne
Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K+, Ca2+, and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces...
February 10, 2018: Acta Neuropathologica
Ying Fu, Yaping Yan
Cerebral small vessel disease (CSVD) is one of the main causes of vascular dementia in older individuals. Apart from risk containment, efforts to prevent or treat CSVD are ineffective due to the unknown pathogenesis of the disease. CSVD, a subtype of stroke, is characterized by recurrent strokes and neurodegeneration. Blood-brain barrier (BBB) impairment, chronic inflammatory responses, and leukocyte infiltration are classical pathological features of CSVD. Understanding how BBB disruption instigates inflammatory and degenerative processes may be informative for CSVD therapy...
2018: Frontiers in Immunology
Geoffrey Potjewyd, Samuel Moxon, Tao Wang, Marco Domingos, Nigel M Hooper
Neurovascular dysfunction is a central process in the pathogenesis of stroke and most neurodegenerative diseases, including Alzheimer's disease. The multicellular neurovascular unit (NVU) combines the neural, vascular and extracellular matrix (ECM) components in an important interface whose correct functioning is critical to maintain brain health. Tissue engineering is now offering new tools and insights to advance our understanding of NVU function. Here, we review how the use of novel biomaterials to mimic the mechanical and functional cues of the ECM, coupled with precisely layered deposition of the different cells of the NVU through 3D bioprinting, is revolutionising the study of neurovascular function and dysfunction...
February 5, 2018: Trends in Biotechnology
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
Zheng Zhang, Linlei Zhang, Jiaou Chen, Yungang Cao, Man Qu, Xinda Lin, Zhao Han, Xunming Ji
BACKGROUND: We showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia. METHODS: Rats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO)...
February 2, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Maria Ribecco-Lutkiewicz, Caroline Sodja, Julie Haukenfrers, Arsalan S Haqqani, Dao Ly, Peter Zachar, Ewa Baumann, Marguerite Ball, Jez Huang, Marina Rukhlova, Marzia Martina, Qing Liu, Danica Stanimirovic, Anna Jezierski, Mahmud Bani-Yaghoub
We have developed a renewable, scalable and transgene free human blood-brain barrier model, composed of brain endothelial cells (BECs), generated from human amniotic fluid derived induced pluripotent stem cells (AF-iPSC), which can also give rise to syngeneic neural cells of the neurovascular unit. These AF-iPSC-derived BECs (i-BEC) exhibited high transendothelial electrical resistance (up to 1500 Ω cm2) inducible by astrocyte-derived molecular cues and retinoic acid treatment, polarized expression of functional efflux transporters and receptor mediated transcytosis triggered by antibodies against specific receptors...
January 30, 2018: Scientific Reports
Robin Sachdeva, Andrea Schlotterer, Dagmar Schumacher, Christin Matka, Ilka Mathar, Nadine Dietrich, Rebekka Medert, Ulrich Kriebs, Jihong Lin, Peter Nawroth, Lutz Birnbaumer, Thomas Fleming, Hans-Peter Hammes, Marc Freichel
OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6-/- compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types...
January 5, 2018: Molecular Metabolism
Georgette Oni, Whitney Chow, Venkat Ramakrishnan, Matthew Griffiths
BACKGROUND: Portable high-frequency ultrasound is a useful adjunct to a plastic surgeon's practice. With a short learning curve, this patient-friendly imaging modality has a variety of uses that aid patient management/treatment plans. The authors describe clinical cases and review the literature regarding ultrasound performed by the surgeon. METHODS: The Sonosite S-Nerve machine with the L25X transducer was used (depth, 4.3 cm). Clinical cases that ordinarily would have been referred to the radiology department were taken from the day-to-day practice of the senior author (M...
February 2018: Plastic and Reconstructive Surgery
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