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https://www.readbyqxmd.com/read/29456537/understanding-progressive-multifocal-leukoencephalopathy-risk-in-multiple-sclerosis-patients-treated-with-immunomodulatory-therapies-a-bird-s-eye-view
#1
REVIEW
Elizabeth A Mills, Yang Mao-Draayer
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456504/a-review-on-central-nervous-system-effects-of-gastrodin
#2
REVIEW
Yuan Liu, Jialiang Gao, Min Peng, Hongyan Meng, Hongbo Ma, Pingping Cai, Yuan Xu, Qiong Zhao, Guomin Si
Rhizoma Gastrodiae (also known as Tian ma ), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae . Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29455449/role-of-exosomes-derived-from-mir-133b-modified-mscs-in-an-experimental-rat-model-of-intracerebral-hemorrhage
#3
Haitao Shen, Xiyang Yao, Haiying Li, Xiang Li, Tiejun Zhang, Qing Sun, Chengyuan Ji, Gang Chen
Intracerebral hemorrhage (ICH) has poor outcomes due to high mortality and morbidity, but until now, the effective treatments remain limited. MicroRNAs (miRNAs) are vital regulators of gene expression and demonstrated to be linked to the pathogenesis of various central nervous system (CNS) diseases. Exosomes are considered as cell-to-cell communication vectors and secreted largely by mesenchymal stromal cells (MSCs). The present study investigated the role of miR-133b delivered by exosomes secreted from MSCs to brain tissues in rats after ICH...
February 17, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29454581/emerging-roles-of-microglial-cathepsins-in-neurodegenerative-disease
#4
REVIEW
Jessica R Lowry, Andis Klegeris
Alzheimer's disease (AD) is one of the leading causes of dementia, and its prevalence is expected to increase dramatically due to the aging global population. Microglia-driven neuroinflammation may contribute to the progression of AD. Microglia, the immune cells of the central nervous system (CNS), become chronically activated by the pathological proteins of AD including amyloid-β peptides (Aβ). Such adversely activated microglia secrete mediators that promote inflammation and damage neurons. Cathepsins are proteases that are expressed by all brain cell types, and most of them are found both intra- and extra-cellularly...
February 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29454102/inflammation-as-a-possible-link-between-dyslipidemia-and-alzheimer-s-disease
#5
REVIEW
Bruno Cabral de Lima Oliveira, Paula Maria Quaglio Bellozi, Helton José Reis, Antônio Carlos Pinheiro de Oliveira
Alzheimer's disease (AD) is the leading cause of dementia worldwide. This pathological condition is characterized not only by Aβ and tau accumulation in the central nervous system (CNS), but also by inflammation, processes that can lead to neurodegeneration. Besides that, other factors may contribute to the development of AD, such as dyslipidemias. Changes in lipid levels can either influence the activity of enzymes related to the protein deposition that occurs in this pathological condition, or enhance the peripheral and CNS immune responses...
February 14, 2018: Neuroscience
https://www.readbyqxmd.com/read/29453990/atp-activated-p2x7-receptor-in-the-pathophysiology-of-mood-disorders-and-as-an-emerging-target-for-the-development-of-novel-antidepressant-therapeutics
#6
REVIEW
Linyu Wei, Sharifah A Syed Mortadza, Jing Yan, Libin Zhang, Lu Wang, Yaling Yin, Chaokun Li, Sylvie Chalon, Patrick Emond, Catherine Belzung, Dongliang Li, Chengbiao Lu, Sebastien Roger, Lin-Hua Jiang
Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response...
February 14, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29453976/cell-type-specific-expression-of-constitutively-active-rheb-promotes-regeneration-of-bulbospinal-respiratory-axons-following-cervical-sci
#7
Mark W Urban, Biswarup Ghosh, Laura R Strojny, Cole G Block, Sara M Blazejewski, Megan C Wright, George M Smith, Angelo C Lepore
Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of injured rVRG axons via targeted induction of Rheb (ras homolog enriched in brain), a signaling molecule that regulates neuronal-intrinsic axon growth potential...
February 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29451203/a-growing-field-the-regulation-of-axonal-regeneration-by-wnt-signaling
#8
REVIEW
Armando L Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S Hackam
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29450696/neuroprotective-effects-of-melatonin-on-experimental-allergic-encephalomyelitis-mice-via-anti-oxidative-stress-activity
#9
Ting Long, Yuan Yang, Ling Peng, Zuoxiao Li
Multiple sclerosis (MS) is a chronic auto-inflammatory disease of the central nervous system (CNS) and hard to heal. This study aimed to investigate the effect of melatonin on mice with experimental autoimmune encephalomyelitis (EAE), a widely used MS model, and its potential mechanism underlying the action of MT on anti-oxidative stress. Female C57BL/6 mice were injected with MOG35-55 peptide to set up the EAE model, and for detection of the effect of melatonin (10 mg/kg i.p.) on the development and progression of EAE...
February 15, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29450650/access-to-the-cns-biomarker-strategies-for-dopaminergic-treatments
#10
REVIEW
Willem Johan van den Brink, Semra Palic, Isabelle Köhler, Elizabeth Cunera Maria de Lange
Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i...
February 15, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29449807/atrial-natriuretic-peptide-acts-as-a-neuroprotective-agent-in-in-vitro-models-of-parkinson-s-disease-via-up-regulation-of-the-wnt-%C3%AE-catenin-pathway
#11
Arianna Colini Baldeschi, Eugenia Pittaluga, Federica Andreola, Simona Rossi, Mauro Cozzolino, Giuseppe Nicotera, Gianluca Sferrazza, Pasquale Pierimarchi, Annalucia Serafino
In the last decades increasing evidence indicated a crucial role of the Wnt/β-catenin signaling in development of midbrain dopaminergic (mDA) neurons. Recently dysregulation of this pathway has been proposed as a novel pathomechanism leading to Parkinson's disease (PD) and some of the molecules participating to the signaling have been evaluated as potential therapeutic targets for PD. Atrial natriuretic peptide (ANP) is a cardiac-derived hormone having a critical role in cardiovascular homeostasis. ANP and its receptors (NPRs) are widely expressed in mammalian central nervous system (CNS) where they could be implicated in the regulation of neural development, synaptic transmission and information processing, as well as in neuroprotection...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29448258/altered-long-noncoding-rna-and-messenger-rna-expression-in-experimental-intracerebral-hemorrhage-a-preliminary-study
#12
Cui Hanjin, Liu Tao, Li Pengfei, Yang Ali, Zhou Huajun, Luo Jiekun, Wang Yang, Tang Tao
BACKGROUND/AIMS: Functional recovery in the chronic phase is a difficult problem in intracerebral hemorrhage (ICH) treatment. Long noncoding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in post-ICH injury and repair are poorly understood, especially those that may be attributed to long-term neurological deficit. The present study depicted the lncRNA and messenger RNA (mRNA) profile by microarray at late stage after an experimental ICH...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29447242/a-novel-ligand-on-astrocytes-interacts-with-natural-cytotoxicity-receptor-nkp44-regulating-immune-response-mediated-by-nk-cells
#13
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
https://www.readbyqxmd.com/read/29446949/positive-and-negative-allosteric-modulators-of-n-methyl-d-aspartate-nmda-receptors-structure-activity-relationships-and-mechanisms-of-action
#14
Erica S Burnell, Mark W Irvine, Guangyu Fang, Kiran Sapkota, David E Jane, Daniel T Monaghan
Excitatory activity in the CNS is predominately mediated by L-glutamate through several families of L-glutamate neurotransmitter receptors. Of these, the N-methyl-D-aspartate receptor (NMDAR) family has many critical roles in CNS function and in various neuropathological and psychiatric conditions. Until recently, the types of compounds available to regulate NMDAR function have been quite limited in terms of mechanism of action, subtype selectivity, and biological effect. However, several new classes of NMDAR agents have now been identified that are positive or negative allosteric modulators (PAMs and NAMs, respectively) with various patterns of NMDAR subtype selectivity...
February 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29445154/interleukin-4-modulates-microglia-homeostasis-and-attenuates-the-early-slowly-progressive-phase-of-amyotrophic-lateral-sclerosis
#15
Chiara Rossi, Melania Cusimano, Martina Zambito, Annamaria Finardi, Alessia Capotondo, Jose Manuel Garcia-Manteiga, Giancarlo Comi, Roberto Furlan, Gianvito Martino, Luca Muzio
Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4-via a lentiviral-mediated gene therapy strategy-skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445144/lenalidomide-regulates-cns-autoimmunity-by-promoting-m2-macrophages-polarization
#16
Qinjie Weng, Jiaying Wang, Jiajia Wang, Jing Wang, Fahmida Sattar, Zhikang Zhang, Jiahuan Zheng, Zijie Xu, Mengting Zhao, Xuan Liu, Lijun Yang, Guifeng Hao, Liang Fang, Q Richard Lu, Bo Yang, Qiaojun He
Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444299/early-nodal-and-paranodal-disruption-in-autoimmune-optic-neuritis
#17
Aleksandar Stojic, Jovana Bojcevski, Sarah K Williams, Ricarda Diem, Richard Fairless
Disturbances in the nodes of Ranvier are an early phenomenon in many CNS disorders, including the autoimmune demyelinating disease multiple sclerosis (MS). Using an animal model of optic neuritis, a common early symptom of MS, we have investigated nodal and paranodal compartments in the optic nerve during disease progression. Both nodes and paranodes, as identified by immunohistochemistry against sodium channels (Nav) and Caspr, respectively, were observed to increase in length during the late induction phase of the disease, prior to onset of the demyelination and immune cell infiltration characteristic of optic neuritis...
February 10, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29440425/bryostatin-1-alleviates-experimental-multiple-sclerosis
#18
Michael D Kornberg, Matthew D Smith, Hasti Atashi Shirazi, Peter A Calabresi, Solomon H Snyder, Paul M Kim
Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29440260/chromatin-remodeler-chd7-regulates-the-stem-cell-identity-of-human-neural-progenitors
#19
MuhChyi Chai, Tsukasa Sanosaka, Hironobu Okuno, Zhi Zhou, Ikuko Koya, Satoe Banno, Tomoko Andoh-Noda, Yoshikuni Tabata, Rieko Shimamura, Tetsutaro Hayashi, Masashi Ebisawa, Yohei Sasagawa, Itoshi Nikaido, Hideyuki Okano, Jun Kohyama
Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE-neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome...
January 15, 2018: Genes & Development
https://www.readbyqxmd.com/read/29438845/-brain-over-body-a-study-on-the-willful-regulation-of-autonomic-function-during-cold-exposure
#20
Otto Muzik, Kaice T Reilly, Vaibhav A Diwadkar
The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a unique set of individuals known for extreme cold tolerance. Here we present a case study of a 57-year old Dutch national, Wim Hof, the so-called "Iceman", with the ability to withstand frequent prolonged periods of extreme cold exposure based on the practice of a self-developed technique involving a combination of forced breathing, cold exposure and meditation (collectively referred to as the Wim Hof Method, henceforth "WHM")...
February 10, 2018: NeuroImage
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