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Blood brain barrie

Barry W Festoff, Ravi K Sajja, Patrick van Dreden, Luca Cucullo
BACKGROUND: The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer's disease (AD) that precedes the hallmarks of amyloid beta (amyloid β) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive...
2016: Journal of Neuroinflammation
Barry I Freedman, Crystal A Gadegbeku, R Nick Bryan, Nicholette D Palmer, Pamela J Hicks, Lijun Ma, Michael V Rocco, S Carrie Smith, Jianzhao Xu, Christopher T Whitlow, Benjamin C Wagner, Carl D Langefeld, Amret T Hawfield, Jeffrey T Bates, Alan J Lerner, Dominic S Raj, Mohammad S Sadaghiani, Robert D Toto, Jackson T Wright, Donald W Bowden, Jeff D Williamson, Kaycee M Sink, Joseph A Maldjian, Nicholas M Pajewski, Jasmin Divers
To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58...
August 2016: Kidney International
Allison E Cherry, Brian R Haas, Alipi V Naydenov, Susan Fung, Cong Xu, Katie Swinney, Michael Wagenbach, Jennifer Freeling, David A Canton, Jonathan Coy, Eric A Horne, Barry Rickman, Juan Jesus Vicente, John D Scott, Rodney J Y Ho, Denny Liggitt, Linda Wordeman, Nephi Stella
Glioblastoma multiforme is a devastating and intractable type of cancer. Current antineoplastic drugs do not improve the median survival of patients diagnosed with glioblastoma multiforme beyond 14 to 15 months, in part because the blood-brain barrier is generally impermeable to many therapeutic agents. Drugs that target microtubules (MT) have shown remarkable efficacy in a variety of cancers, yet their use as glioblastoma multiforme treatments has also been hindered by the scarcity of brain-penetrant MT-targeting compounds...
September 2016: Molecular Cancer Therapeutics
Caitlin A Orsini, Barry Setlow, Michael DeJesus, Stacy Galaviz, Kimberly Loesch, Thomas Ioerger, Deeann Wallis
BACKGROUND: The Latrophilin 3 (LPHN3) gene (recently renamed Adhesion G protein-coupled receptor L3 (ADGRL3)) has been linked to susceptibility to attention deficit/hyperactivity disorder (ADHD) and vulnerability to addiction. However, its role and function are not well understood as there are no known functional variants. METHODS: To characterize the function of this little known gene, we phenotyped Lphn3 null mice. We assessed motivation for food reward and working memory via instrumental responding tasks, motor coordination via rotarod, and depressive-like behavior via forced swim...
May 2016: Molecular Genetics & Genomic Medicine
John J Leddy, John G Baker, Barry Willer
Concussion is a physiological brain injury with physical, cognitive, and emotional sequelae. The macrophysiological insult to the brain affects the autonomic nervous system and its control of cerebral blood flow. Most patients recover within 2 weeks, but some do not. Persistence of symptoms beyond the generally accepted time frame for recovery is called post-concussion syndrome (PCS). PCS is not a single entity; it is a group of disorders that requires specific forms of therapy. Rest has been the mainstay of the treatment for concussion and PCS...
May 2016: Physical Medicine and Rehabilitation Clinics of North America
Stuart D Dowall, Victoria A Graham, Emma Rayner, Barry Atkinson, Graham Hall, Robert J Watson, Andrew Bosworth, Laura C Bonney, Samantha Kitchen, Roger Hewson
Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies...
May 2016: PLoS Neglected Tropical Diseases
Peter S Pang, John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Joshua Kriger, Margaret F Prescott, Tsushung A Hua, Thomas Severin, Marco Metra
OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo...
July 2016: JACC. Heart Failure
Luis M Colon-Perez, Kelvin Tran, Khalil Thompson, Michael C Pace, Kenneth Blum, Bruce A Goldberger, Mark S Gold, Adriaan W Bruijnzeel, Barry Setlow, Marcelo Febo
The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex...
August 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Rishma Vidyasagar, Laurence Abernethy, Barry Pizer, Shivaram Avula, Laura M Parkes
OBJECTIVE: Arterial spin-labelling (ASL) MRI uses intrinsic blood water to quantify the cerebral blood flow (CBF), removing the need for the injection of a gadolinium-based contrast agent used for conventional perfusion imaging such as dynamic susceptibility contrast (DSC). Owing to the non-invasive nature of the technique, ASL is an attractive option for use in paediatric patients. This work compared DSC and multi-timepoint ASL measures of CBF in paediatric brain tumours. METHODS: Patients (n = 23; 20 low-grade tumours and 3 high-grade tumours) had DSC and multi-timepoint ASL with and without vascular crushers (VC)...
June 2016: British Journal of Radiology
Stephen Hughes, John Barry, Jeremy Russell, Robert Bell, Som Gurung
How blood was able to reach the heads of the long-necked sauropod dinosaurs has long been a matter of debate and several hypotheses have been presented. For example, it has been proposed that sauropods had exceptionally large hearts, multiple 'normal' sized hearts spaced at regular intervals up the neck or held their necks horizontal, or that the siphon effect was in operation. By means of an experimental model, we demonstrate that the siphon principle is able to explain how blood was able to adequately perfuse the sauropod brain...
April 15, 2016: Journal of Experimental Biology
Shimelis Dagnachew, Getachew Terefe, Getachew Abebe, Asegedech Sirak, Enrico Bollo, Dave Barry, Bruno Goddeeris
BACKGROUND: The Northwest region of Ethiopia is affected by both tsetse and non-tsetse transmitted trypanosomosis with a huge impact on livestock productivity. The objective of this experimental study was to determine clinical and pathological findings in young Zebu cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia. A total of 18 cattle (Bos indicus) aged between 6 and 12 months, purchased from a trypanosome-free and confirmed to be trypanosome negative divided into three groups of six animals were used...
2015: BMC Veterinary Research
Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Isaac Odame, Beng Fuh, Alex George, William Owen, Lori Luchtman-Jones, Zora R Rogers, Lee Hilliard, Cynthia Gauger, Connie Piccone, Margaret T Lee, Janet L Kwiatkowski, Sherron Jackson, Scott T Miller, Carla Roberts, Matthew M Heeney, Theodosia A Kalfa, Stephen Nelson, Hamayun Imran, Kerri Nottage, Ofelia Alvarez, Melissa Rhodes, Alexis A Thompson, Jennifer A Rothman, Kathleen J Helton, Donna Roberts, Jamie Coleman, Melanie J Bonner, Abdullah Kutlar, Niren Patel, John Wood, Linda Piller, Peng Wei, Judy Luden, Nicole A Mortier, Susan E Stuber, Naomi L C Luban, Alan R Cohen, Sara Pressel, Robert J Adams
BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada...
February 13, 2016: Lancet
Brian C Sayers, Nigel J Walker, Joseph H Roycroft, Dori R Germolec, Gregory L Baker, Mark L Clark, Barry K Hayden, Henry DeFord, Jeffrey A Dill, Amit Gupta, Matthew D Stout
C60 fullerenes (C60) are spherical structures consisting of 60 carbon atoms that are generated via combustion from both natural and anthropogenic sources. C60 are also synthesized intentionally for industrial applications. Individual C60 structures have an approximate diameter of 1nm; however, C60 readily forms aggregates and typically exist as larger particles that range from nanometers to micrometers in diameter. In this report, lung and extrapulmonary tissue deposition and lung clearance of C60 nanoparticles (nano-C60, 50nm) and microparticles (micro-C60, 1μm) were examined in Wistar Han rats and B6C3F1/N mice after nose-only inhalation for 90 days...
January 2, 2016: Toxicology
Margaret M Redfield, Kevin J Anstrom, James A Levine, Gabe A Koepp, Barry A Borlaug, Horng H Chen, Martin M LeWinter, Susan M Joseph, Sanjiv J Shah, Marc J Semigran, G Michael Felker, Robert T Cole, Gordon R Reeves, Ryan J Tedford, W H Wilson Tang, Steven E McNulty, Eric J Velazquez, Monica R Shah, Eugene Braunwald
BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks...
December 10, 2015: New England Journal of Medicine
Laura M Raffield, Amanda J Cox, Barry I Freedman, Christina E Hugenschmidt, Fang-Chi Hsu, Benjamin C Wagner, Jianzhao Xu, Joseph A Maldjian, Donald W Bowden
AIMS: To examine the relationships between type 2 diabetes (T2D) status, glycemic control, and T2D duration with magnetic resonance imaging (MRI)-derived neuroimaging measures in European Americans from the Diabetes Heart Study (DHS) Mind cohort. METHODS: Relationships were examined using marginal models with generalized estimating equations in 784 participants from 514 DHS Mind families. Fasting plasma glucose, glycated hemoglobin, and diabetes duration were analyzed in 682 participants with T2D...
June 2016: Acta Diabetologica
Oleg Otlivanchik, Nicole M Sanders, Ambrose Dunn-Meynell, Barry E Levin
While the neural control of glucoregulatory responses to insulin-induced hypoglycemia is beginning to be elucidated, brain sites responsible for behavioral responses to hypoglycemia are relatively poorly understood. To help elucidate central control mechanisms associated with hypoglycemia unawareness, we first evaluated the effect of recurrent hypoglycemia on a simple behavioral measure, the robust feeding response to hypoglycemia, in rats. First, food intake was significantly, and similarly, increased above baseline saline-induced intake (1...
January 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Laura M Raffield, Gretchen A Brenes, Amanda J Cox, Barry I Freedman, Christina E Hugenschmidt, Fang-Chi Hsu, Jianzhao Xu, Benjamin C Wagner, Jeff D Williamson, Joseph A Maldjian, Donald W Bowden
AIMS: Anxiety, depression, accelerated cognitive decline, and increased risk of dementia are observed in individuals with type 2 diabetes. Anxiety and depression may contribute to lower performance on cognitive tests and differences in neuroimaging observed in individuals with type 2 diabetes. METHODS: These relationships were assessed in 655 European Americans with type 2 diabetes from 504 Diabetes Heart Study families. Participants completed cognitive testing, brain magnetic resonance imaging, the Brief Symptom Inventory Anxiety subscale, and the Center for Epidemiologic Studies Depression-10...
January 2016: Journal of Diabetes and its Complications
Ernesto Caballero-Garrido, Juan Carlos Pena-Philippides, Tamar Lordkipanidze, Denis Bragin, Yirong Yang, Erik Barry Erhardt, Tamara Roitbak
A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR-155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO...
September 9, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Dirk A Ridder, Jan Wenzel, Kristin Müller, Kathrin Töllner, Xin-Kang Tong, Julian C Assmann, Stijn Stroobants, Tobias Weber, Cristina Niturad, Lisanne Fischer, Beate Lembrich, Hartwig Wolburg, Marilyn Grand'Maison, Panayiota Papadopoulos, Eva Korpos, Francois Truchetet, Dirk Rades, Lydia M Sorokin, Marc Schmidt-Supprian, Barry J Bedell, Manolis Pasparakis, Detlef Balschun, Rudi D'Hooge, Wolfgang Löscher, Edith Hamel, Markus Schwaninger
Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood-brain barrier (BBB), and epileptic seizures...
September 21, 2015: Journal of Experimental Medicine
Heath G Gasier, Ivan T Demchenko, Barry W Allen, Claude A Piantadosi
The endogenous vasodilator and signaling molecule nitric oxide has been implicated in cerebral hyperemia, sympathoexcitation, and seizures induced by hyperbaric oxygen (HBO2) at or above 3 atmospheres absolute (ATA). It is unknown whether these events in the onset of central nervous system oxygen toxicity originate within specific brain structures and whether blood flow is diverted to the brain from peripheral organs with high basal flow, such as the kidney. To explore these questions, total and regional cerebral blood flow (CBF) were measured in brain structures of the central autonomic network in anesthetized rats in HBO2 at 6 ATA...
December 1, 2015: Journal of Applied Physiology
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