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brain endothelium

Bob Smit, Yvo M Smulders, Etto C Eringa, Heleen M Oudemans-van Straaten, Armand R J Girbes, Kimberley E Wever, Carlijn R Hooijmans, Angelique M E Spoelstra-de Man
BACKGROUND: Arterial hyperoxia may induce vasoconstriction and reduce cardiac output, which is particularly undesirable in patients who already have compromised perfusion of vital organs. Due to the inaccessibility of vital organs in humans, vasoconstrictive effects of hyperoxia have primarily been studied in animal models. However, the results of these studies vary substantially. Here, we investigate the variation in magnitude of the hyperoxia effect among studies and explore possible sources of heterogeneity, such as vascular region and animal species...
August 4, 2018: Critical Care: the Official Journal of the Critical Care Forum
Jia Pei Chan, Bernice H Wong, Cheen Fei Chin, Dwight L A Galam, Juat Chin Foo, Loo Chin Wong, Sujoy Ghosh, Markus R Wenk, Amaury Cazenave-Gassiot, David L Silver
Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic acid (DHA). Brain acquisition of DHA is primarily mediated by the transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed in the endothelium of the blood-brain barrier (BBB) and other abundant cell types within the brain. Mfsd2a transports DHA and other polyunsaturated fatty acids (PUFAs) esterified to lysophosphatidylcholine (LPC-DHA). However, the function of Mfsd2a and DHA in brain development is incompletely understood...
August 3, 2018: PLoS Biology
Andrée-Anne Berthiaume, David A Hartmann, Mark W Majesky, Narayan R Bhat, Andy Y Shih
The biology of brain microvascular pericytes is an active area of research and discovery, as their interaction with the endothelium is critical for multiple aspects of cerebrovascular function. There is growing evidence that pericyte loss or dysfunction is involved in the pathogenesis of Alzheimer's disease, vascular dementia, ischemic stroke and brain injury. However, strategies to mitigate or compensate for this loss remain limited. In this review, we highlight a novel finding that pericytes in the adult brain are structurally dynamic in vivo , and actively compensate for loss of endothelial coverage by extending their far-reaching processes to maintain contact with regions of exposed endothelium...
2018: Frontiers in Aging Neuroscience
Andrea Berenyiova, Ima Dovinova, Miroslava Kvandova, Frantisek Kristek, Eugene Jansen, Miroslava Majzunova, Sona Cacanyiova
Although the role of nitric oxide (NO) in essential hypertension is still unclear, the effects of long-term NO deficiency have not yet been investigated during the critical juvenile period in spontaneously hypertensive rats (SHR). We aimed to analyze the effects of chronic NO synthase (NOS) inhibition on systolic blood pressure (sBP), vasoactivity, morphological changes and superoxide level in the thoracic aorta (TA), NOS activity in different tissues, and general biomarkers of oxidative stress in plasma of young SHR...
2018: Oxidative Medicine and Cellular Longevity
László Tóth, Dávid Szöllősi, Katalin Kis-Petik, István Adorján, Ferenc Erdélyi, Mihály Kálmán
The immediate alterations following lesions cannot be investigated by using fixed tissues. Here, we employed two-photon microscopy to study the alterations to the permeability of blood-brain barrier and to glio-vascular connections in vivo during the first minutes following cortical lesions in mice. Four models were used: (1) cryogenic lesion, (2) photodisruption using laser pulses, (3) photothrombosis, and (4) bilateral carotid ligation. Sulforhodamine101 was used for supravital labeling of astrocytes and dextran-bound fluorescein isothiocyanate for the assessment of extravasation...
July 26, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Steffen E Storck, Anika M S Hartz, Jessica Bernard, Andrea Wolf, André Kachlmeier, Anne Mahringer, Sascha Weggen, Jens Pahnke, Claus U Pietrzik
The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells...
July 21, 2018: Brain, Behavior, and Immunity
Helena Parfenova, Massroor Pourcyrous, Alexander L Fedinec, Jianxiong Liu, Shymali Basuroy, Charles W Leffler
Neonatal asphyxia leads to cerebrovascular disease and neurological complications via a mechanism that may involve oxidative stress. Carbon monoxide (CO) is an antioxidant messenger produced via a heme oxygenase (HO)-catalyzed reaction. Cortical astrocytes are the major cells in the brain that express constitutive HO-2 isoform. We tested the hypothesis that CO, produced by astrocytes, has cerebroprotective properties during neonatal asphyxia. We developed a survival model of prolonged asphyxia in newborn pigs that combines insults of severe hypoxia, hypercapnia, and acidosis while avoiding extreme hypotension and cerebral blood flow reduction...
July 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Eliza W Beal, Curtis Dumond, Jung-Lye Kim, Clifford Akateh, Emre Eren, Katelyn Maynard, Chandan K Sen, Jay L Zweier, Kenneth Washburn, Bryan A Whitson, Sylvester M Black
There is a significant shortage of liver allografts available for transplantation, and in response the donor criteria have been expanded. As a result, normothermic ex vivo liver perfusion (NEVLP) has been introduced as a method to evaluate and modify organ function. NEVLP has many advantages in comparison to hypothermic and subnormothermic perfusion including reduced preservation injury, restoration of normal organ function under physiologic conditions, assessment of organ performance, and as a platform for organ repair, remodeling, and modification...
June 27, 2018: Journal of Visualized Experiments: JoVE
Limin Wu, Joon Y Chung, Shivani Saith, Lorenzo Tozzi, Erin M Buckley, Bharat Sanders, Maria A Franceschini, Sevda Lule, Saef Izzy, Josephine Lok, William J Edmiston, Lauren M McAllister, Sloane Mebane, Gina Jin, Jiaxi Lu, John S Sherwood, Sarah Willwerth, Suzanne Hickman, Joseph El Khoury, Eng H Lo, David Kaplan, Michael J Whalen
Repetitive mild traumatic brain injury during adolescence can induce neurological dysfunction through undefined mechanisms. Interleukin-1 (IL-1) contributes to experimental adult diffuse and contusion TBI models, and IL-1 antagonists have entered clinical trials for severe TBI in adults; however, no such data exist for adolescent TBI. We developed an adolescent mouse repetitive closed head injury (rCHI) model to test the role of IL-1 family members in post-injury neurological outcome. Compared to one CHI, three daily injuries (3HD) produced acute and chronic learning deficits and emergence of hyperactivity, without detectable gliosis, neurodegeneration, brain atrophy, and white matter loss at one year...
July 13, 2018: Journal of Cerebral Blood Flow and Metabolism
Andrea P Falanga, Pietro Melone, Roberta Cagliani, Nicola Borbone, Stefano D'Errico, Gennaro Piccialli, Paolo A Netti, Daniela Guarnieri
The development of new strategies for enhancing drug delivery to the brain represents a major challenge in treating cerebral diseases. In this paper, we report on the synthesis and structural characterization of a biocompatible nanoparticle (NP) made up of poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) co-polymer (namely PELGA) functionalized with the membranotropic peptide gH625 (gH) and the iron-mimicking peptide CRTIGPSVC (CRT) for transport across the blood-brain barrier (BBB). gH possesses a high translocation potency of the cell membrane...
July 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Lucy Z Kornblith, Anamaria J Robles, Amanda S Conroy, Carolyn M Hendrickson, Carolyn S Calfee, Alexander T Fields, Rachael A Callcut, Mitchell J Cohen
BACKGROUND: Injury to the blood brain barrier exposes endothelium rich in von Willebrand factor (vWF) which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance which induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole blood multiple electrode platelet aggregometry...
July 5, 2018: Journal of Trauma and Acute Care Surgery
Tien-Yao Tsai, Iat-Lon Leong, Ka-Shun Cheng, Lian-Ru Shiao, Tzu-Hui Su, Kar-Lok Wong, Paul Chan, Yuk-Man Leung
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low-density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium-dependent relaxation (EDR) and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC-induced cytotoxicity in brain EC. In this work we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND...
July 5, 2018: Fundamental & Clinical Pharmacology
Slava Rom, Viviana Zuluaga-Ramirez, Sachin Gajghate, Alecia Seliga, Malika Winfield, Nathan A Heldt, Mikhail A Kolpakov, Yulia V Bashkirova, Abdel Karim Sabri, Yuri Persidsky
End organ injury in diabetes mellitus (DM) is driven by microvascular compromise (including diabetic retinopathy and nephropathy). Cognitive impairment is a well-known complication of DM types 1 and 2; however, its mechanism(s) is(are) not known. We hypothesized that blood-brain barrier (BBB) compromise plays a key role in cognitive decline in DM. Using a DM type 1 model (streptozotocin injected C57BL/6 mice) and type 2 model (leptin knockout obese db/db mice), we showed enhanced BBB permeability and memory loss (Y maze, water maze) that are associated with hyperglycemia...
July 5, 2018: Molecular Neurobiology
Elizaveta B Boitsova, Andrey V Morgun, Elena D Osipova, Elena A Pozhilenkova, Galina P Martinova, Olga V Frolova, Raissa Ya Olovannikova, Abolghasem Tohidpour, Yana V Gorina, Yulia A Panina, Alla B Salmina
BACKGROUND: Lipopolysaccharide (LPS) is one of the main constituents of the cell wall of gram-negative bacteria. As an endotoxin, LPS induces neuroinflammation, which is associated with the blood-brain barrier impairment. Lactate is a metabolite with some significant physiological functions within the neurovascular unit/blood-brain barrier (BBB). Accumulation of extracellular and cerebrospinal fluid lactate is a specific feature of bacterial meningitis. However, the role of lactate production, transport, and sensing by lactate receptors GPR81 in the pathogenesis of bacterial neuroinflammation is still unknown...
July 4, 2018: Journal of Neuroinflammation
Michael M Wang, Xiaojie Zhang, Soo Jung Lee, Snehaa Maripudi, Richard F Keep, Allison M Johnson, Svetlana M Stamatovic, Anuska V Andjelkovic
Regulation of cerebral endothelial cell function plays an essential role in changes in blood-brain barrier permeability. Proteins that are important for establishment of endothelial tight junctions have emerged as critical molecules, and PDZ domain containing-molecules are among the most important. We have discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells. Surprisingly, PRX protein is not detected in brain endothelium in other mammalian species, suggesting that it could confer human-specific vascular properties...
July 3, 2018: Scientific Reports
Max Masthoff, Sandra Gran, Xueli Zhang, Lydia Wachsmuth, Michael Bietenbeck, Anne Helfen, Walter Heindel, Lydia Sorokin, Johannes Roth, Michel Eisenblätter, Moritz Wildgruber, Cornelius Faber
Time-lapse MRI was implemented for dynamic non-invasive cell tracking of individual slowly moving intravascular immune cells. Repetitive MRI acquisition enabled dynamic observation of iron oxide nanoparticle (ION) labelled cells. Simulations of MRI contrast indicated that only cells moving slower than 1 µm/s were detectable. Time-lapse MRI of the brain was performed after either IONs or ION-labelled monocytes were injected intravenously into naïve and experimental autoimmune encephalomyelitis (EAE) bearing mice at a presymptomatic or symptomatic stage...
June 22, 2018: Scientific Reports
Nebojsa Mihajlica, Christer Betsholtz, Margareta Hammarlund-Udenaes
Pericytes are perivascular cells that play important roles in the regulation of the blood-brain barrier (BBB) properties. Pericyte-deficiency causes compromised BBB integrity and increase in permeability to different macromolecules mainly by upregulated transcytosis. The aim of the present study was to investigate pericyte involvement in the extent of small-molecular drug transport across the BBB. This was performed with five compounds: diazepam, digoxin, levofloxacin, oxycodone and paliperidone. Compounds were administered at low doses via subcutaneous injections as a cassette (simultaneously) to pericyte-deficient Pdgfbret/ret mice and corresponding WT controls...
June 20, 2018: European Journal of Pharmaceutical Sciences
Keren Kaufman-Francis, Julianne T Djordjevic, Pierre-Georges Juillard, Sophie Lev, Desmarini Desmarini, Georges E R Grau, Tania C Sorrell
The innate immune system is the primary defense against cryptococcal infection, but paradoxically it promotes infection of the central nervous system. We performed a detailed longitudinal study of neurocryptococcosis in normal, chimeric, green fluorescent protein phagocyte-positive mice and phagocyte-depleted mice and interrogated the central nervous system innate immune response to Cryptococcus neoformans H99 using confocal microscopy, histology, flow cytometry, and quantification of brain cytokine/chemokines and fungal burdens...
July 2018: American Journal of Pathology
Youhai Li, Natalia Lapina, Nina Weinzierl, Lothar Schilling
Focal brain ischemia markedly affects cerebrovascular reactivity. So far, these changes have mainly been related to alterations in the level of smooth muscle cell function while alterations of the endothelial lining have not yet been studied in detail. We have, therefore, investigated the effects of ischemia/reperfusion injury on bradykinin (BK)-induced relaxation since BK is an important mediator of tissue inflammation and affects vascular function in an endothelium-dependent manner. Focal brain ischemia was induced in rats by endovascular filament occlusion (2h) of the middle cerebral artery (MCA)...
2018: PloS One
Gianni Allais, Giulia Chiarle, Silvia Sinigaglia, Gisella Airola, Paola Schiapparelli, Chiara Benedetto
Migraine has a predilection for female sex and the course of symptoms is influenced by life stage (presence of menstrual cycle, pregnancy, puerperium, menopause) and use of hormone therapy, such as hormonal contraception and hormone replacement therapy. Hormonal changes figure among common migraine triggers, especially sudden estrogen drop. Moreover, estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation, and they interact with the vascular endothelium of the brain...
June 2018: Neurological Sciences
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