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CNS disease

Jeffrey Lambe, Olwen C Murphy, Shiv Saidha
PURPOSE OF REVIEW: With the recognition that neurodegeneration represents the principal substrate of disability in multiple sclerosis (MS), there has been increased strives towards identifying biomarkers for accurately quantifying and tracking neurodegeneration during the disease course. The retina provides an opportune "window" into the central nervous system (CNS) in MS, with retinal changes in MS reflecting not only local, but also global aspects of neurodegeneration and inflammation operative in the disease...
March 21, 2018: Current Treatment Options in Neurology
Denise C Hsu, Piyanate Sunyakumthorn, Matthew Wegner, Alexandra Schuetz, Decha Silsorn, Jacob D Estes, Claire Deleage, Khamis Tomusange, Samir K Lakhashe, Ruth M Ruprecht, Eric Lombardini, Rawiwan Im-Erbsin, Yanin Kuncharin, Yuwadee Phuang-Ngern, Dutsadee Inthawong, Weerawan Chuenarom, Robin Burke, Merlin L Robb, Lishomwa C Ndhlovu, Jintanat Ananworanich, Victor Valcour, Robert J O'Connell, Serena Spudich, Nelson L Michael, Sandhya Vasan
Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neuro AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this non-accelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4 T+ cell counts mirrored early HIV infection in humans. At 12 weeks post infection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process...
March 21, 2018: Journal of Virology
Jianjia Fan, Rui Qi Zhao, Cameron Parro, Wenchen Zhao, Hsien-Ya Chou, Jerome Robert, Tarek Z Deeb, Carina Raynoschek, Samantha Barichievy, Ola Engvist, Marcello Maresca, Ryan Hicks, Johan Meuller, Stephen J Moss, Nicholas J Brandon, Michael W Wood, Iva Kulic, Cheryl L Wellington
Apolipoprotein E (apoE) is the primary lipid carrier within the central nervous system (CNS) and the strongest genetic risk factor for late onset Alzheimer's disease (AD). ApoE is primarily lipidated via the ATP-binding cassette transporter 1 (ABCA1), and both are under transcriptional regulation by the liver X nuclear receptor (LXR). Considerable evidence from genetic (using ABCA1 overexpression) and pharmacological (using synthetic LXR agonists) studies in AD mouse models suggests that increased levels of lipidated apoE can improve cognitive performance and, in some strains, can reduce amyloid burden...
March 21, 2018: Journal of Lipid Research
Félix Hernández, María Llorens-Martín, Marta Bolós, Mar Pérez, Raquel Cuadros, Noemí Pallas-Bazarra, Juan C Zabala, Jesús Avila
Alzheimer's disease (AD) is characterized by the presence of two aberrant structures: namely senile plaques, composed of amyloid-β peptide (Aβ), and neurofibrillary tangles, composed of tau protein. In this regard, Aβ and tau protein have been widely studied in research efforts aiming to find a therapy for AD. Aβ and tau pathologies do not always overlap. The precursor of Aβ is expressed in peripheral tissues and in the central nervous system (CNS), whereas tau is mainly a neuronal protein. Since AD is a disease of the CNS, it has been proposed that Aβ may initiate the disease process, with tau being the executor...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Skanda Rajasundaram
Our increasing appreciation of adenosine as an endogenous signaling molecule that terminates inflammation has generated excitement regarding the potential to target adenosine receptors (ARs) in the treatment of multiple sclerosis (MS), a disease of chronic neuroinflammation. Of the four G protein-coupled ARs, A2ARs are the principal mediator of adenosine's anti-inflammatory effects and accordingly, there is a growing body of evidence surrounding the role of A2ARs in experimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS...
2018: Frontiers in Immunology
Hana Malikova, Miroslava Burghardtova, Eva Koubska, Vaclav Mandys, Tomas Kozak, Jiri Weichet
Background: Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive disease, which is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. According to previous reports, SCNSL presents mostly with leptomeningeal spread; however, our experience differs. In the present study, we demonstrate the diversity of magnetic resonance imaging (MRI) patterns in SCNSL. Patients and methods: Initial morphological MRI findings in 21 patients (10 women and 11 men with mean age 62...
2018: Neuropsychiatric Disease and Treatment
Anna Moniuszko-Malinowska, Paweł Penza, Piotr Czupryna, Olga Zajkowska, Sławomir Pancewicz, Renata Świerzbińska, Justyna Dunaj, Joanna Zajkowska
AIM: The aim of the study was to determine HMGB-1 concentration in serum and cerebrospinal fluid (CSF) of patients suffering from tick-borne encephalitis (TBE) and neuroborreliosis (NB). We focused on HMGB-1 measurement in CSF or sera in order to establish whether it could help to differentiate between NB and TBE. METHODS: 80 patients with meningitis and meningoencephalitis were enrolled in the study. Patients were divided into two groups: Group I - patients with NB (n=40) and Group II - patients with TBE (n=40)...
March 17, 2018: International Journal of Infectious Diseases: IJID
Hailong Li, Zhongyuan Tang, Peng Chu, Yanlin Song, Ying Yang, Bin Sun, Mengyue Niu, Eskandar Qaed, Abdullah Shopit, Guozhu Han, Xiaodong Ma, Jinyong Peng, Min Hu, Zeyao Tang
Methylglyoxal (MGO), an active metabolite of glucose, is observed in high levels in the tissues and blood of diabetic patients. Phosphocreatine (PCr), a high-energy phosphate compound, exhibits a range of pharmacological actions but little is well known of its neuroprotective action. The aim of the present study was to investigate the neuroprotective effects and the possible mechanisms of PCr. Diabetes is closely associated with neurodegenerative diseases, leading not only to the peripheral nervous system (PNS) and but also to central nervous system (CNS) damage...
March 17, 2018: Free Radical Biology & Medicine
Jessica M Hogestyn, David J Mock, Margot Mayer-Proschel
Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining characteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors...
February 2018: Neural Regeneration Research
Samira EghbaliFeriz, Akram Taleghani, Zahra Tayarani-Najaran
Scutellaria comprises many species traditionally used for cognitive and neurological conditions. In vitro and in vivo studies have supported the value of bioactive compounds of the genus Scutellaria for CNS disorders such as Alzheimer, cerebral ischemia, depression and anxiety. In particular, the effects of plants belonging to the genus Scutellaria and their components are detailed on cognitive ability such as memory, attention and learning. In this review, the pharmacology of CNS effect and the related molecular mechanisms of the plants belonging to the genus Scutellaria and active constituents have been discussed...
March 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tesfaye W Tefera, Karin Borges
Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1-13 C]glucose and [1,2-13 C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1G93A mice at onset and mid disease stages using high-pressure liquid chromatography,1 H and13 C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3-13 C]lactate, total alanine and [3-13 C]alanine, but not cortical glucose and [1-13 C]glucose, were reduced mostly at mid stage indicating impaired glycolysis...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Aziza Alrafiah, Evangelia Karyka, Ian Coldicott, Kayleigh Iremonger, Katherin E Lewis, Ke Ning, Mimoun Azzouz
Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene ( SMN1 ), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic target. Here, we show reduced levels of PLS3 protein in the brain and spinal cord of a mouse model of SMA. Our study also revealed that lentiviral-mediated PLS3 expression restored axonal length in cultured Smn-deficient motor neurons...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Luigi Cavanna, Pietro Seghini, Camilla Di Nunzio, Elena Orlandi, Emanuele Michieletti, Elisa Maria Stroppa, Patrizia Mordenti, Chiara Citterio, Stefano Vecchia, Adriano Zangrandi
Central nervous system (CNS) metastases from cancers of the gastrointestinal tract (GIT) are rare, and occur in 0.16-0.69% of patients with gastric or gastro-esophageal (GE) junction cancer. Overexpression of the human epidermal growth factor 2 (HER-2) is associated with poor prognosis in the absence of HER-2-targeted therapy, and with an increased incidence of CNS metastases in patients with breast cancer. The role of HER-2 overexpression in CNS metastases is not well known in gastric adenocarcinoma. The purpose of the present retrospective study was to assess the incidence of CNS metastases and to evaluate the associations between the CNS and HER-2 status in a series of consecutive patients with gastric or GE junction cancer...
April 2018: Oncology Letters
Srikant Rangaraju, Syed Ali Raza, Noel Xiang'An Li, Ranjita Betarbet, Eric B Dammer, Duc Duong, James J Lah, Nicholas T Seyfried, Allan I Levey
In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells, neurons, and pathological protein aggregates, such as Aβ in Alzheimer's disease (AD). While CD11b+ CD45low microglia account for the majority of CNS MPs, a small population of CD11b+ CD45high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally and pathologically unique CD45high cells have unclear origin and undefined phagocytic characteristics...
2018: Frontiers in Immunology
Phillip Mackie, Joe Lebowitz, Leila Saadatpour, Emily Nickoloff, Peter Gaskill, Habibeh Khoshbouei
The second-most common neurodegenerative disease, Parkinson Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission...
March 15, 2018: Brain, Behavior, and Immunity
Danica M Sutherland, Pavithra Aravamudhan, Terence S Dermody
Viruses are constantly engaged in a molecular arms race with the host, where efficient and tactical use of cellular receptors benefits critical steps in infection. Receptor use dictates initiation, establishment, and spread of viral infection to new tissues and hosts. Mammalian orthoreoviruses (reoviruses) are pervasive pathogens that use multiple receptors to overcome protective host barriers to disseminate from sites of initial infection and cause disease in young mammals. In particular, reovirus invades the central nervous system (CNS) with serotype-dependent tropism and disease...
2018: Advances in Virus Research
Freja Aksel Jacobsen, Alexander N Scherer, Jeppe Mouritsen, Hera Bragadóttir, B Thomas Bäckström, Samra Sardar, Dan Holmberg, Anthony J Koleske, Åsa Andersson
Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development...
March 17, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Patrick Belikan, Ulrike Bühler, Christina Wolf, Gautam K Pramanik, René Gollan, Frauke Zipp, Volker Siffrin
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS. Myelin-specific CD4+ Th lymphocytes are known to play a major role in both MS and its animal model experimental autoimmune encephalomyelitis (EAE). CCR7 is a critical element for immune cell trafficking and recirculation, that is, lymph node homing, under homeostatic conditions; blocking CCR7+ central memory cells from egress of lymph nodes is a therapeutic approach in MS. To define the effect of CD4+ T cell-specific constitutive deletion of CCR7 in the priming and effector phase in EAE, we used an active EAE approach in T cell reconstituted Rag1-/- mice, as well as adoptive transfer EAE, in which mice received in vitro-primed CCR7-/- or CCR7+/+ myelin Ag TCR-transgenic 2d2 Th17 cells...
March 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Andrea K H Stavoe, Erika L F Holzbaur
Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the distal axon occurs via a conserved pathway that is required to maintain functional synapses and prevent axon degeneration. Autophagosomes are formed de novo at the axon terminal in a stepwise assembly process, engulfing mitochondrial fragments, aggregated proteins, and bulk cytosol in what appears to be a nonselective uptake mechanism. Following formation, autophagosomes fuse with late endosomes/lysosomes and then are rapidly and efficiently transported along the axon toward the soma, driven by the microtubule motor cytoplasmic dynein...
March 13, 2018: Neuroscience Letters
Moumita Datta, Ori Staszewski, Elena Raschi, Maximilian Frosch, Nora Hagemeyer, Tuan Leng Tay, Thomas Blank, Mario Kreutzfeldt, Doron Merkler, Stephanie Ziegler-Waldkirch, Patrick Matthias, Melanie Meyer-Luehmann, Marco Prinz
Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, Hdac1 and Hdac2. Prenatal ablation of Hdac1 and Hdac2 impaired microglial development. Mechanistically, the promoters of pro-apoptotic and cell cycle genes were hyperacetylated in absence of Hdac1 and Hdac2, leading to increased apoptosis and reduced survival...
March 20, 2018: Immunity
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