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https://www.readbyqxmd.com/read/28890893/proximate-mediators-of-microvascular-dysfunction-at-the-blood-brain-barrier-neuroinflammatory-pathways-to-neurodegeneration
#1
REVIEW
Barry W Festoff, Ravi K Sajja, Luca Cucullo
Current projections are that by 2050 the numbers of people aged 65 and older with Alzheimer's disease (AD) in the US may increase threefold while dementia is projected to double every 20 years reaching ~115 million by 2050. AD is clinically characterized by progressive dementia and neuropathologically by neuronal and synapse loss, accumulation of amyloid plaques, and neurofibrillary tangles (NFTs) in specific brain regions. The preclinical or presymptomatic stage of AD-related brain changes may begin over 20 years before symptoms occur, making development of noninvasive biomarkers essential...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28844425/amygdala-activation-as-a-marker-for-selective-attention-toward-neutral-faces-in-a-chronic-traumatic-brain-injury-population
#2
Leanne R Young, Weikei Yu, Michael Holloway, Barry N Rodgers, Sandra B Chapman, Daniel C Krawczyk
There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces...
September 2017: Neuropsychologia
https://www.readbyqxmd.com/read/28768727/manipulating-glucose-metabolism-during-different-stages-of-viral-pathogenesis-can-have-either-detrimental-or-beneficial-effects
#3
Siva Karthik Varanasi, Dallas Donohoe, Ujjaldeep Jaggi, Barry T Rouse
This report deals with physiological changes and their implication following ocular infection with HSV. This infection usually results in a blinding inflammatory reaction in the cornea, orchestrated mainly by proinflammatory CD4 T cells and constrained in severity by regulatory T cells. In the present report, we make the unexpected finding that blood glucose levels change significantly during the course of infection. Whereas levels remained normal during the early phase of infection when the virus was actively replicating in the cornea, they increased around 2-fold during the time when inflammatory responses to the virus was occurring...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716943/visualizing-context-dependent-calcium-signaling-in-encephalitogenic-t-cells-in-vivo-by-two-photon-microscopy
#4
Nikolaos I Kyratsous, Isabel J Bauer, Guokun Zhang, Marija Pesic, Ingo Bartholomäus, Marsilius Mues, Ping Fang, Miriam Wörner, Stephanie Everts, Joachim W Ellwart, Joanna M Watt, Barry V L Potter, Reinhard Hohlfeld, Hartmut Wekerle, Naoto Kawakami
In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28546320/a-cohort-mortality-study-of-lead-exposed-workers-in-the-usa-finland-and-the-uk
#5
Kyle Steenland, Vaughn Barry, Ahti Anttila, Markku Sallmén, Damien McElvenny, A C Todd, Kurt Straif
OBJECTIVES: To investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study. METHODS: We conducted internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates...
November 2017: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28539079/a-cognitive-stressor-for-event-related-potential-studies-the-portland-arithmetic-stress-task
#6
Rachel Atchley, Roger Ellingson, Daniel Klee, Tabatha Memmott, Barry Oken
In this experiment, we developed and evaluated the Portland Arithmetic Stress Task (PAST) as a cognitive stressor to evaluate acute and sustained stress reactivity for event-related potential (ERP) studies. The PAST is a titrated arithmetic task adapted from the Montreal Imaging Stress Task (MIST), with added experimental control over presentation parameters, improved and synchronized acoustic feedback and generation of timing markers needed for physiological analyzes of real-time brain activity. Thirty-one older adults (M = 60 years) completed the PAST...
June 19, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#7
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28412449/targeted-drug-delivery-system-to-neural-cells-utilizes-the-nicotinic-acetylcholine-receptor
#8
Rachel Huey, Barry O'Hagan, Paul McCarron, Susan Hawthorne
Drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. In order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (BBB) must be overcome. This work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (RDP). Characterization studies revealed that RDP could be conjugated to drug-loaded PLGA nanoparticles of average diameter 257...
April 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28395539/unlocking-the-box-basic-requirements-for-an-ideal-ventricular-assist-device-controller
#9
Alexander L Medvedev, Jamshid H Karimov, Barry D Kuban, David J Horvath, Nader Moazami, Kiyotaka Fukamachi
A modern ventricular assist device (VAD) system comprises an implantable rotary blood pump and external components located outside the patient's body: a wearable controller connected to the pump via a percutaneous cable, wearable rechargeable batteries, battery charger, alternating- and direct-current power supplies, and a hospital device to control and monitor the system. If the blood pump is the 'heart' of a VAD system, the controller is its 'brain.' The controller drives the pump's electrical motor; varies the pump speed or flow based on user commands or feedback signals; collects, processes, and stores data; performs self-diagnostics; transmits to and receives data from other system components, i...
April 19, 2017: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/28319499/developmental-venous-anomalies-mimicking-neoplasm-on-11c-methionine-pet-and-dsc-perfusion-mri
#10
Julie H Harreld, Mikhail Doubrovin, Elizabeth R Butch, Angela Edwards, Barry Shulkin
Elevated relative cerebral blood volume on perfusion MRI and increased uptake on C-methionine PET can be used to diagnose and guide biopsy of brain tumors but are not specific. We report increased uptake on C-methionine PET associated with 4 developmental venous anomalies (DVAs) in 3 children with brain tumors, which could potentially mimic tumor and misdirect biopsy. Because DVAs are not readily visible on CT, prevention of misdirected biopsy in patients with focally elevated C-methionine uptake and relative cerebral blood volume relies on close correlation with contrast-enhanced anatomic MRI to exclude DVA or other nonneoplastic etiology...
May 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28276534/non-invasive-assessment-of-cerebral-blood-flow-and-oxygen-metabolism-in-neonates-during-hypothermic-cardiopulmonary-bypass-feasibility-and-clinical-implications
#11
Silvina L Ferradal, Koichi Yuki, Rutvi Vyas, Christopher G Ha, Francesca Yi, Christian Stopp, David Wypij, Henry H Cheng, Jane W Newburger, Aditya K Kaza, Maria A Franceschini, Barry D Kussman, P Ellen Grant
The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197303/optimization-of-3-pyrimidin-4-yl-oxazolidin-2-ones-as-allosteric-and-mutant-specific-inhibitors-of-idh1
#12
Julian R Levell, Thomas Caferro, Gregg Chenail, Ina Dix, Julia Dooley, Brant Firestone, Pascal D Fortin, John Giraldes, Ty Gould, Joseph D Growney, Michael D Jones, Raviraj Kulathila, Fallon Lin, Gang Liu, Arne Mueller, Simon van der Plas, Kelly Slocum, Troy Smith, Remi Terranova, B Barry Touré, Viraj Tyagi, Trixie Wagner, Xiaoling Xie, Ming Xu, Fan S Yang, Liping X Zhou, Raymond Pagliarini, Young Shin Cho
High throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1(R132H). Synthesis of the four separate stereoisomers identified the (S,S)-diastereomer (IDH125, 1f) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1(wt). Initial structure-activity relationship exploration identified the key tolerances and potential for optimization. X-ray crystallography identified a functionally relevant allosteric binding site amenable to inhibitors, which can penetrate the blood-brain barrier, and aided rational optimization...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28140493/cerebral-high-intensity-transient-signals-during-pediatric-cardiac-catheterization-a-pilot-study-using-transcranial-doppler-ultrasonography
#13
Kerri L LaRovere, Kush Kapur, Doff B McElhinney, Alexander Razumovsky, Barry D Kussman
BACKGROUND AND PURPOSE: Cerebral emboli are one potential cause of acute brain injury in children with congenital heart disease (CHD) undergoing cardiac catheterization. In this pilot study using transcranial Doppler (TCD) ultrasonography, we sought to evaluate the incidence, burden, and circumstances of cerebral high-intensity transient signals (HITS), presumably representing emboli, during pediatric cardiac catheterization. METHODS: Emboli monitoring of the right middle cerebral artery was performed in five children...
January 31, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28139719/a-functional-il22-polymorphism-rs2227473-is-associated-with-predisposition-to-childhood-cerebral-malaria
#14
Sandrine Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Hélia Dessein, Charlène Couturier, Florence Burté, Aboubacar A Oumar, Biobele J Brown, Abdoualye Traore, Nathaniel K Afolabi, Abdoulaye Barry, Samuel Omokhodion, Wuraola A Shokunbi, Olugbemiro Sodeinde, Ogobara Doumbo, Delmiro Fernandez-Reyes, Alain J Dessein
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27553758/hmgb1-and-thrombin-mediate-the-blood-brain-barrier-dysfunction-acting-as-biomarkers-of-neuroinflammation-and-progression-to-neurodegeneration-in-alzheimer-s-disease
#15
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...
August 24, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27342958/apol1-renal-risk-variants-associate-with-reduced-cerebral-white-matter-lesion-volume-and-increased-gray-matter-volume
#16
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
https://www.readbyqxmd.com/read/27325686/st-11-a-new-brain-penetrant-microtubule-destabilizing-agent-with-therapeutic-potential-for-glioblastoma-multiforme
#17
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
https://www.readbyqxmd.com/read/27247960/behavioral-and-transcriptomic-profiling-of-mice-null-for-lphn3-a-gene-implicated-in-adhd-and-addiction
#18
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
https://www.readbyqxmd.com/read/27154855/active-rehabilitation-of-concussion-and-post-concussion-syndrome
#19
REVIEW
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
https://www.readbyqxmd.com/read/27149521/a-susceptible-mouse-model-for-zika-virus-infection
#20
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
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