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Biomarkers neurological damage

Davide Ferrari, Nicoletta Bianchi, Holger K Eltzschig, Roberto Gambari
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of silencing mRNA targets. miRNA dysregulation has been linked to cancer development, cardiovascular and neurological diseases, lipid metabolism, and impaired immunity. Therefore, miRNAs are gaining interest as putative novel disease biomarkers and therapeutic targets. Recent studies have shown that purinergic surface receptors activated by extracellular nucleotides (ATP, ADP, UTP, UDP), and by nucleosides such as adenosine (ADO), are subject to miRNA regulation...
October 2016: Trends in Molecular Medicine
Salvatore Mazzeo, Roberto Santangelo, Maria Paola Bernasconi, Giordano Cecchetti, Agnese Fiorino, Patrizia Pinto, Gabriella Passerini, Monica Falautano, Giancarlo Comi, Giuseppe Magnani
BACKGROUND: Correctly diagnosing Alzheimer's disease (AD) in prodromal phases would allow the adoption of experimental therapeutic strategies that could selectively interrupt the pathogenetic process before neuronal damage becomes irreversible. Therefore, great efforts have been aimed at finding early reliable disease markers. OBJECTIVE: The aim of this study was to identify a simple, cost effective, and reliable diagnostic algorithm to predict conversion from mild cognitive impairment (MCI) to AD...
October 18, 2016: Journal of Alzheimer's Disease: JAD
D Allan Butterfield, Tanea T Reed
Traumatic brain injury (TBI) is a spontaneous event in which sudden trauma and secondary injury cause brain damage. Symptoms of TBI can range from mild to severe depending on extent of injury. The outcome can span from complete patient recovery to permanent memory loss and neurological decline. Currently, there is no known cure for TBI; however, immediate medical attention after injury is most beneficial for patient recovery. It is a well-established concept that imbalances in the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and native antioxidant mechanisms have been shown to increase oxidative stress...
September 2, 2016: Proteomics. Clinical Applications
Lauren E Himmel, Maryam B Lustberg, A Courtney DeVries, Ming Poi, Ching-Shih Chen, Samuel K Kulp
Minocycline is purported to have neuroprotective properties in experimental models of some human neurologic diseases, and has therefore been identified as a putative neuroprotectant for chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. However, because its mechanism of action is believed to be mediated through anti-inflammatory, anti-apoptotic, and anti-oxidant pathways, co-administration of minocycline with chemotherapeutic agents has the potential to reduce the efficacy of anticancer drugs...
October 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Alejandro Bustamante, Alba Simats, Andrea Vilar-Bergua, Teresa García-Berrocoso, Joan Montaner
Stroke represents one of the most important causes of disability and death in developed countries. However, there is a lack of prognostic tools in clinical practice to monitor the neurological condition and predict the final outcome. Blood biomarkers have been proposed and studied in this indication; however, no biomarker is currently used in clinical practice. The stroke-related neuroinflammatory processes have been associated with a poor outcome in stroke, as well as with poststroke complications. In this review, we focus on the most studied blood biomarkers of this inflammatory processes, cytokines, and C-reactive protein, evaluating its association with outcome and complications in stroke through the literature, and performing a systematic review on the association of C-reactive protein and functional outcome after stroke...
August 18, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Verónica Chaparro-Huerta, Mario Eduardo Flores-Soto, Mario Ernesto Merin Sigala, Juan Carlos Barrera de León, María de Lourdes Lemus-Varela, Blanca Miriam de Guadalupe Torres-Mendoza, Carlos Beas-Zárate
BACKGROUND: Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae...
May 31, 2016: Pediatrics and Neonatology
Patrick Forny, Anke Schumann, Merima Mustedanagic, Déborah Mathis, Marie-Angela Wulf, Nadine Nägele, Claus-Dieter Langhans, Assem Zhakupova, Joerg Heeren, Ludger Scheja, Ralph Fingerhut, Heidi L Peters, Thorsten Hornemann, Beat Thony, Stefan Kölker, Patricie Burda, D Sean Froese, Olivier Devuyst, Matthias R Baumgartner
Methylmalonic aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the newborn period with failure to thrive and metabolic crisis leading to coma or even death. Survivors remain at risk of metabolic decompensations and severe long term complications, notably renal failure and neurological impairment. We generated clinically relevant mouse models of MMAuria using a constitutive Mut knock-in (KI) allele based on the p.Met700Lys patient mutation, used homozygously (KI/KI) or combined with a knockout allele (KO/KI), to study biochemical and clinical MMAuria disease aspects...
September 23, 2016: Journal of Biological Chemistry
Alex P Di Battista, Shawn G Rhind, Doug Richards, Nathan Churchill, Andrew J Baker, Michael G Hutchison
The long-term health effects of concussion and sub-concussive impacts in sport are unknown. Growing evidence suggests both inflammation and neurodegeneration are pivotal to secondary injury processes and the etiology of neurodegenerative diseases. In the present study we characterized circulating brain injury and inflammatory mediators in healthy male and female athletes according to concussion history and collision sport participation. Eighty-seven university level athletes (male, n = 60; female, n = 27) were recruited before the start of the competitive season...
2016: PloS One
Doodipala Samba Reddy, Aamir Bhimani, Ramkumar Kuruba, Min Jung Park, Farida Sohrabji
This Review describes the current status of poststroke epilepsy (PSE) with an emphasis on poststroke epileptogenesis modeling for testing new therapeutic agents. Stroke is a leading cause of epilepsy in an aging population. Late-onset "epileptic" seizures have been reported in up to 30% cases after stroke. Nevertheless, the overall prevalence of PSE is 2-4%. Rodent models of stroke have contributed to our understanding of the relationship between seizures and the underlying ischemic damage to neurons. To understand whether acutely generated stroke events lead to a chronic phenotype more closely resembling PSE with recurrent seizures, a limited variety of approaches emerged in early 2000s...
July 25, 2016: Journal of Neuroscience Research
Shay P McGuinness, Rachael L Parke, Kate Drummond, Tim Willcox, Michael Bailey, Cornelius Kruger, Megan Baker, Keri-Anne Cowdrey, Eileen Gilder, Lianne McCarthy, Thomas Painter
BACKGROUND: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels...
September 2016: Anesthesiology
Magda A Lam, Ghassan J Maghzal, Mohsen Khademi, Fredik Piehl, Rikke Ratzer, Jeppe Romme Christensen, Finn Thorup Sellebjerg, Tomas Olsson, Roland Stocker
OBJECTIVE: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS). METHODS: We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein)...
August 2016: Neurology® Neuroimmunology & Neuroinflammation
Grzegorz Kloc, Małgorzata Budziak, Agnieszka Więckiewicz, Mateusz Pleśniak, Halina Bartosik-Psujek
Diagnosis of relapsing-remitting multiple sclerosis requires demonstration disseminated symptoms in time and space on the basis of neurological assessment or magnetic resonance imaging findings. In addition, the diagnosis is conditioned by ruling out other conditions that may explain the clinical symptoms. We describe the patient presenting in the initial stage of the disease neurological symptoms and magnetic resonance imaging lesions, that met criteria for relapsing-remitting multiple sclerosis diagnosis...
July 2016: Neurologia i Neurochirurgia Polska
Consuelo Chafer-Pericas, María Cernada, Leena Rahkonen, Vedran Stefanovic, Sture Andersson, Máximo Vento
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) has deleterious neurological consequences. To identify patients at risk of neuronal damage deserving implementation of neuroprotective strategies clinicians have relied on prenatal sentinel events, postnatal clinical assessment (Apgar score), and blood gas analysis. This feasibility study aimed to assess if lipid peroxidation byproducts associated with neuronal damage correlated with cord blood metabolic acidemia in patients with HIE. POPULATION AND METHODS: This is a case/control study in which cases were newborn infants with severe acidemia (pH<7...
August 2016: Free Radical Biology & Medicine
Biao Yan, Junhui Guo, Xudong Liu, Jinquan Li, Xu Yang, Ping Ma, Yang Wu
Among all phthalate esters, dibutyl phthalate (DBP) is only second to di-(2-ethylhexyl) phthalate (DEHP) in terms of adverse health outcomes, and its potential cerebral neurotoxicity has raised concern in recent years. DBP exposure has been reported to be responsible for neurobehavioral effects and related neurological diseases. In this study, we found that neurobehavioral changes induced by DBP may be mediated by oxidative damage in the mouse brain, and that the co-administration of Mangiferin (MAG, 50mg/kg/day) may protect the brain against oxidative damage caused by DBP exposure...
July 2016: Environmental Toxicology and Pharmacology
Guoliang Yu, Ye Liang, Ziming Huang, Deron W Jones, Kirkwood A Pritchard, Hao Zhang
BACKGROUND: Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. METHODS: To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO...
2016: Journal of Neuroinflammation
Sean M Tobyne, Daria Boratyn, Jessica A Johnson, Douglas N Greve, Caterina Mainero, Eric C Klawiter
The functional organization of the human brain consists of a high degree of connectivity between interhemispheric homologous regions. The degree of homotopic organization is known to vary across the cortex and homotopic connectivity is high in regions that share cross-hemisphere structural connections or are activated by common input streams (e.g., the visual system). Damage to one or both regions, as well as damage to the connections between homotopic regions, could disrupt this functional organization. Here were introduce and test a computationally efficient technique, surface-based homotopic interhermispheric connectivity (sHIC), that leverages surface-based registration and processing techniques in an attempt to improve the spatial specificity and accuracy of cortical interhemispheric connectivity estimated with resting state functional connectivity...
August 2016: Human Brain Mapping
Alex P Di Battista, Sandro B Rizoli, Brandon Lejnieks, Arimie Min, Maria Y Shiu, Henry T Peng, Andrew J Baker, Michael G Hutchison, Nathan Churchill, Kenji Inaba, Bartolomeu B Nascimento, Airton Leonardo de Oliveira Manoel, Andrew Beckett, Shawn G Rhind
BACKGROUND: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. OBJECTIVES: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. PATIENTS AND METHODS: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed...
September 2016: Shock
Marco Capolupo, Paola Valbonesi, Alisar Kiwan, Sara Buratti, Silvia Franzellitti, Elena Fabbri
The occurrence of caffeine (CF), a biologically active drug, has widely been documented in coastal waters, and whether its environmental concentrations do represent a threat for marine organisms is unclear. The present study aimed at assessing sub-lethal effects induced by a 7-day exposure to environmentally relevant concentrations of CF (5, 50 and 500ng/L) in the Mediterranean mussel, Mytilus galloprovincialis. CF in water and mussel tissues, and a battery of biomarkers, including lysosomal parameters of general stress, oxidative stress responses and endpoints of neurological and genetic damages, were evaluated and tested for significance vs controls (p<0...
September 1, 2016: Science of the Total Environment
José Luis Guerrero-Orriach, Daniel Ariza-Villanueva, Ana Florez-Vela, Lourdes Garrido-Sánchez, María Isabel Moreno-Cortés, Manuel Galán-Ortega, Alicia Ramírez-Fernández, Juan Alcaide Torres, Concepción Santiago Fernandez, Isabel Navarro Arce, José María Melero-Tejedor, Manuel Rubio-Navarro, José Cruz-Mañas
PURPOSE: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. METHODS: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan...
2016: Therapeutics and Clinical Risk Management
Mehri Igci, Mehmet Baysan, Remzi Yigiter, Mustafa Ulasli, Sirma Geyik, Recep Bayraktar, İbrahim Bozgeyik, Esra Bozgeyik, Ali Bayram, Ecir Ali Cakmak
Multiple sclerosis (MS) is an imflammatory disease of central nervous system caused by genetic and environmental factors that remain largely unknown. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Malfunction of autophagy contributes to the pathogenesis of neurological diseases, and autophagy genes may modulate the T cell survival. We aimed to examine the expression levels of autophagy-related genes. The blood samples of 95 unrelated patients (aged 17-65years, 37 male, 58 female) diagnosed as MS and 95 healthy controls were used to extract the RNA samples...
August 15, 2016: Gene
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