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Katherine M Satrom, Kathleen Ennis, Brian M Sweis, Tatyana M Matveeva, Jun Chen, Leif Hanson, Akhil Maheshwari, Raghavendra Rao
BACKGROUND: Hyperglycemia is common in extremely low gestational age newborns (ELGAN) and is associated with increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population, but the specific effects of hyperglycemia on the developing hippocampus are not known. METHODS: The objective of this study was to determine the acute and long-term effects of hyperglycemia on the developing hippocampus in neonatal rats using a streptozotocin (STZ)-induced model of hyperglycemia...
March 15, 2018: Journal of Neuroinflammation
Elena Rodriguez-Vieitez, Agneta Nordberg
The recent progress in the development of in vivo biomarkers is rapidly changing how neurodegenerative diseases are conceptualized and diagnosed, and how clinical trials are designed today. Alzheimer's disease (AD)-the most common neurodegenerative disorder-is characterized by a complex neuropathology involving the deposition of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT) of hyperphosphorylated tau proteins, accompanied by the activation of glial cells-astrocytes and microglia-and neuroinflammatory responses, leading to neurodegeneration and cognitive dysfunction...
2018: Methods in Molecular Biology
Srinivasu Kallakuri, Edward Pace, Huichao Lu, Hao Luo, John Cavanaugh, Jinsheng Zhang
Blast exposure is an increasingly significant health hazard and can have a range of debilitating effects, including auditory dysfunction and traumatic brain injury. To assist in the development of effective treatments, a greater understanding of the mechanisms of blast-induced auditory damage and dysfunction, especially in the central nervous system, is critical. To elucidate this area, we subjected rats to a unilateral blast exposure at 22 psi, measured their auditory brainstem responses (ABRs), and histologically processed their brains at 1 day, 1 month, and 3-month survival time points...
2018: PloS One
Katrin Pfuhlmann, Sonja C Schriever, Beata Legutko, Peter Baumann, Luke Harrison, Dhiraj G Kabra, Emily Violette Baumgart, Matthias H Tschöp, Cristina Garcia-Caceres, Paul T Pfluger
ᅟ: Astrocytosis is a reactive process involving cellular, molecular, and functional changes to facilitate neuronal survival, myelin preservation, blood brain barrier function and protective glial scar formation upon brain insult. The overall pro- or anti-inflammatory impact of reactive astrocytes appears to be driven in a context- and disease-driven manner by modulation of astrocytic Ca2+ homeostasis and activation of Ca2+/calmodulin-activated serine/threonine phosphatase calcineurin. Here, we aimed to assess whether calcineurin is dispensable for astrocytosis in the hypothalamus driven by prolonged high fat diet (HFD) feeding...
February 8, 2018: Journal of Neuroinflammation
James P Orengo, Meike E van der Heijden, Shuang Hao, Jianrong Tang, Harry T Orr, Huda Y Zoghbi
Spinocerebellar ataxia type 1 (SCA1) is characterized by adult-onset cerebellar degeneration with attendant loss of motor coordination. Bulbar function is eventually impaired, and patients tend to die from inability to clear the airway. We asked whether motor neuron degeneration is at the root of bulbar dysfunction by studying SCA1 knock-in mice. We analyzed spinal cord and brainstem motor neurons in SCA1 knock-in (Atxn1154Q) mice at 1, 3, and 6 months of age. Specifically, we assessed breathing physiology, diaphragm histology and electromyography, and motor neuron histology and immunohistochemistry...
January 29, 2018: Disease Models & Mechanisms
Raffaella Rusconi, Ayse Ulusoy, Helia Aboutalebi, Donato A Di Monte
Increased expression of α-synuclein can initiate its long-distance brain transfer, representing a potential mechanism for pathology spreading in age-related synucleinopathies, such as Parkinson's disease. In this study, the effects of overexpression-induced α-synuclein transfer were assessed over a 1-year period after injection of viral vectors carrying human α-synuclein DNA into the rat vagus nerve. This treatment causes targeted overexpression within neurons in the dorsal medulla oblongata and subsequent diffusion of the exogenous protein toward more rostral brain regions...
January 30, 2018: Aging Cell
Chad A Tagge, Andrew M Fisher, Olga V Minaeva, Amanda Gaudreau-Balderrama, Juliet A Moncaster, Xiao-Lei Zhang, Mark W Wojnarowicz, Noel Casey, Haiyan Lu, Olga N Kokiko-Cochran, Sudad Saman, Maria Ericsson, Kristen D Onos, Ronel Veksler, Vladimir V Senatorov, Asami Kondo, Xiao Z Zhou, Omid Miry, Linnea R Vose, Katisha R Gopaul, Chirag Upreti, Christopher J Nowinski, Robert C Cantu, Victor E Alvarez, Audrey M Hildebrandt, Erich S Franz, Janusz Konrad, James A Hamilton, Ning Hua, Yorghos Tripodis, Andrew T Anderson, Gareth R Howell, Daniela Kaufer, Garth F Hall, Kun P Lu, Richard M Ransohoff, Robin O Cleveland, Neil W Kowall, Thor D Stein, Bruce T Lamb, Bertrand R Huber, William C Moss, Alon Friedman, Patric K Stanton, Ann C McKee, Lee E Goldstein
The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration...
January 18, 2018: Brain: a Journal of Neurology
Susmita Sil, Palsamy Periyasamy, Ming-Lei Guo, Shannon Callen, Shilpa Buch
A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR)...
January 17, 2018: Molecular Neurobiology
Adriana B Silva, Dolores A Bravo-Duran, Jose R Eguibar, Carmen Cortes
Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant...
January 11, 2018: Synapse
Maria Morello, Véréna Landel, Emmanuelle Lacassagne, Kevin Baranger, Cedric Annweiler, François Féron, Pascal Millet
The impairment of hippocampal neurogenesis at the early stages of Alzheimer's disease (AD) is believed to support early cognitive decline. Converging studies sustain the idea that vitamin D might be linked to the pathophysiology of AD and to hippocampal neurogenesis. Nothing being known about the effects of vitamin D on hippocampal neurogenesis in AD, we assessed them in a mouse model of AD. In a previous study, we observed that dietary vitamin D supplementation in female AD-like mice reduced cognitive decline only when delivered during the symptomatic phase...
January 9, 2018: Molecular Neurobiology
Karen Irvine, Robin Bishop, Seok Joon Won, Jianguo Xu, Katherine Hamel, Valerie Coppes, Pardeep Singh, Andrew Sondag, Eric Rome, Jayinee Basu, Giordano Santos, S Scott Panter, Raymond Swanson
The inflammation response induced by brain trauma can impair recovery. This response requires several hours to fully develop, and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation. Here we evaluated delayed treatment with veliparib, a poly(ADP-ribose) polymerase inhibitor currently in clinical trials as a cancer therapeutic, in rats and pigs subjected to controlled cortical impact (CCI)...
December 29, 2017: Journal of Neurotrauma
Nina Kosi, Ivan Alić, Iva Salamon, Dinko Mitrečić
Although transplantation of stem cells improves recovery of the nervous tissue, little is known about the influence of different brain regions on transplanted cells. After we confirmed that cells with uniform differentiation potential can be generated in independent experiments, one million of neural stem cells isolated from B6.Cg-Tg(Thy1-YFP)16Jrs/J mouse embryos were transplanted into the brain 24 hours after induction of stroke. The lateral ventricles, the corpus callosum and the striatum were tested. Two and four weeks after the transplantation, the cells transplanted in all three regions have been attracted to the ischemic core...
December 23, 2017: Neuroscience Letters
Hailin Qin, Jie Qin, Junmin Hu, He Huang, Lianting Ma
BACKGROUND The aim of our study was to evaluate the effect of Malva sylvestris (MS) on cognitive dysfunction in a repetitive mild traumatic brain injury (MTBI). MATERIAL AND METHODS MTBI was induced in all the study animals by hitting a metallic pendulum near the parietal-occipital area of the skull three times a day for ten days. Animals were treated with MS (250 mg/kg and 500 mg/kg) intragastrically per day for seven consecutive days. Cognitive function was estimated by the Morris water maze (MWM) method...
December 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Marcos L Aranda, María F González Fleitas, Hernán H Dieguez, Georgia A Milne, Julián D Devouassoux, María I Keller Sarmiento, Mónica Chianelli, Pablo H Sande, Damián Dorfman, Ruth E Rosenstein
Optic neuritis (ON) is an inflammatory, demyelinating, neurodegenerative, and presently untreatable condition of the optic nerve which might induce blindness. We analyzed the effect of environmental enrichment (EE) on visual pathway damage provoked by experimental ON induced by a microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve. For this purpose, LPS was microinjected into the optic nerve from male Wistar rats. After injection, one group of animals was submitted to EE, and another group remained in standard environment (SE) for 21 days...
December 9, 2017: Neuropharmacology
R Lucá, R Giacominelli-Stuffler, S Mazzariol, S Roperto, C Cocumelli, G DI Guardo
Dolphin morbillivirus (DMV), a highly pathogenic agent, may cause peculiar, "brain-only" forms of infection (BOFDI), in which viral antigen and/or genome is found exclusively in the brain from striped dolphins (Stenella coeruleoalba). These BOFDIs show morphopathological similarities with subacute sclerosing panencephalitis and old dog encephalitis (ODE) in measles virus-infected patients and in canine distemper virus-infected dogs, respectively. The brain tissue from 3 BOFDI-affected striped dolphins was investigated by means of double labelling-indirect immunofluorescence (DL-IIF) and ultrastructurally, in order to characterize the DMV-targeted neuronal and non-neuronal cell populations, along with the associated submicroscopic findings...
2017: Acta Virologica
Rebecca J Holley, Stuart M Ellison, Daniel Fil, Claire O'Leary, John McDermott, Nishanthi Senthivel, Alexander W W Langford-Smith, Fiona L Wilkinson, Zelpha D'Souza, Helen Parker, Aiyin Liao, Samuel Rowlston, Hélène F E Gleitz, Shih-Hsin Kan, Patricia I Dickson, Brian W Bigger
Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells...
January 1, 2018: Brain: a Journal of Neurology
John I Broussard, Laura Acion, Héctor De Jesús-Cortés, Terry Yin, Jeremiah K Britt, Ramiro Salas, Mauro Costa-Mattioli, Claudia Robertson, Andrew A Pieper, David B Arciniegas, Ricardo Jorge
PRIMARY OBJECTIVE: Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour. RESEARCH DESIGN: We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group...
2018: Brain Injury: [BI]
Dianne Langford, Byung Oh Kim, Wei Zou, Yan Fan, Pejman Rahimain, Ying Liu, Johnny J He
HIV-1 Tat is known to be neurotoxic and important for HIV/neuroAIDS pathogenesis. However, the overwhelming majority of the studies involved use of recombinant Tat protein. To understand the contributions of Tat protein to HIV/neuroAIDS and the underlying molecular mechanisms of HIV-1 Tat neurotoxicity in the context of a whole organism and independently of HIV-1 infection, a doxycycline-inducible astrocyte-specific HIV-1 Tat transgenic mouse (iTat) was created. Tat expression in the brains of iTat mice was determined to be in the range of 1-5 ng/ml and led to astrocytosis, loss of neuronal dendrites, and neuroinflammation...
November 15, 2017: Journal of Neurovirology
Elena Vasilskis, Ingrid Kreimerman, Silvia Olivera, Eduardo Savio, Henry Engler
AIM: To compare the uptake of (11)C-deuterodeprenyl ((11)C-DED) and (11)C-methionine ((11)C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. (11)C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies. MATERIALS AND METHODS: Binding and internalization studies of (11)C-MET and (11)C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
Victoria E Thaney, Ana B Sanchez, Jerel A Fields, Arpi Minassian, Jared W Young, Ricky Maung, Marcus Kaul
HIV-1 infection causes injury to the central nervous system (CNS) and is often associated with neurocognitive disorders. One model for brain damage seen in AIDS patients is the transgenic (tg) mouse expressing a soluble envelope protein gp120 of HIV-1 LAV in the brain in astrocytes under the control of the promoter of glial fibrillary acidic protein. These GFAP-gp120tg mice manifest several key neuropathological features observed in AIDS brains, such as decreased synaptic and dendritic density, increased numbers of activated microglia, and pronounced astrocytosis...
October 26, 2017: Journal of Neurovirology
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