DOCSLIB.ORG

(TNF-Α) Inhibits Astrocytic Support of Neuronal Survival and Neurites Outgrowth

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(TNF-Α) Inhibits Astrocytic Support of Neuronal Survival and Neurites Outgrowth Advances in Bioscience and Biotechnology, 2013, 4, 73-80 ABB http://dx.doi.org/10.4236/abb.2013.48A2010 Published Online August 2013 (http://www.scirp.org/journal/abb/) Pro-inflammatory cytokine; tumor-necrosis factor-alpha (TNF-α) inhibits astrocytic support of neuronal survival and neurites outgrowth Ebtesam M. Abd-El-Basset Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait Email: [email protected] Received 16 June 2013; revised 16 July 2013; accepted 31 July 2013 Copyright © 2013 Ebtesam M. Abd-El-Basset. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT 1. INTRODUCTION Reactive astrogliosis has been implicated in the fail- Astrocytes support the CNS neurons, by controlling the ure of axonal regeneration in adult mammalian Cen- microenvironment surrounding the neurons, picking up tral Nervous System (CNS). It is our hypothesis that any excess neurotransmitters or ions that are secreted inflammatory cytokines act upon astrocytes to alter from the neurons during conduction of nerve impulses their biochemical and physical properties, which may and metabolic activity [1,2]. Astrocytes are also impor- in turn be responsible for the failure of neuronal re- tant in secreting several trophic factors, vital to the survi- generation. We have therefore examined the effect of val of neurons [3,4]. Astrocytes can promote neurite out- tumor-necrosis factor-alpha (TNF-α) on the ability of growth both in vitro and in vivo. They express receptors astrocytes to support the survival of the cortical neu- for a variety of growth factors and neurotansmittors [5]. Nerve growth factors production in astrocytes is regula- rons and the growth of the neurites. Mouse astrocytes ted by various cytokines including TNF-α [6]. In addi- and cortical neuronal cultures were prepared. It was tion, astrocytes play a crucial part in the antioxidant de- observed that when neurons were cultured in absence fence of the brain [7]. of astrocytes only a few of them grew and survived However, in cases of insult to the CNS, astrocytes only for 5 - 6 days. These neurons had small cell bo- begin to accumulate at the margin of the injury forming a dies and few, short neurites. However, when the same layer that interfaces between the injury and intact tissues, numbers of neurons were cultured on the top of as- which become known as the glial scar or reactive astrog- trocytes, more neurons grew and survived up to 16 - liosis [8]. Reactive astrogliosis is characterized by an 18 days. They had bigger cell bodies and many long increase in the amount of GFAP which is regulated by branched neurites that formed anestamosing net- hormones, cytokines, and growth factors [9,10]. Al- works. The neurons then coalesced and the neurites though the functional role of the glial scar is not yet formed thick bundles. When the same numbers of completely understood, it has been suggested that the neurons were grown on the top of astrocytes pre- scar inhibits nerve regeneration by acting as a physical treated with TNF-α, few neurons survived up to 13 barrier that neurons cannot penetrate [8,11]. However, days. The neurites of the survived neurons were the formation of the glial scar can also be beneficial in shorter than neurites of neurons grown on normal isolating the damaged region and in preventing the astrocytes and did not form bundles. In addition, spread of the inflammatory response to intact neuronal TNF-α stimulated the expression of glial fibrillary tissue [12,13] thereby helping to limit tissue degenera- acidic protein (GFAP) by astrocytes. These results tion and preserving function after CNS injury. In addi- support that the pro-inflammatory cytokine, TNF-α tion, recent data showed axon regeneration through scars modulates the gliosis and that the astrocytic cell sup- and into sites of chronic spinal cord injury [14]. All these ports neuronal survival and neurite outgrowth. data emphasize that reactive astrocytes play a role in wound healing and restoring CNS function at the site of Keywords: Astrocytes; Neurons; Cytokines; injury. The data also indicate the importance of pre- Tumor-Necrosis Factor-Alpha serving astrocyte populations [13,15,16]. OPEN ACCESS 74 E. M. Abd-El-Basset / Advances in Bioscience and Biotechnology 4 (2013) 73-80 During injury to the CNS, astrocytes are also respon- Guidelines for Care and use of laboratory Animals and sible for the secretion of cytokines, such as interleukin-1 the Guide for the Care and Use of Laboratory animals (IL-1), interleukin-6 (IL-6) and TNF-α [17]. Cytokines (Kuwait University-Faculty of Health Publication). All are responsible for certain changes that take place in the efforts were made to minimize animal suffering, to re- nervous system [18]. It is known that the immune system duce the number of animals used, and to utilize alter- and the nervous system communicate with each other natives to in vivo techniques. through the sharing of biochemical informational sub- stances and their receptors, which is referred to as neu- 2.1. Astrocyte Cultures ral-immune interactions. For instance, several neurotran- The astrocyte cultures were prepared according to the smitters, neuroendocrine hormones and even nerve method of [24]. The cerebral hemispheres of newborn growth factors are produced by immune cells and clearly Balb/c mice were isolated aseptically and the meninges play an important role in the nervous system [4,6]. The were removed. The neopallia was dissected out and then CNS has its own resident immune system in which glia forced through a sterile 75 µm Nitex mesh. The cells cells (astrocytes and microglia) not only serve supportive were suspended in a modified Eagle’s Minimum Essen- and nutritive roles for neurons but also engage from time tial Medium (mMEM) containing 5% horse serum. For to time in several inflammatory processes that defend the culturing, 5 × 104 nigrosine-excluding cells were plated CNS from pathogens and help it to recover from stress in 60 mm Petri dishes containing 22 × 22 mm glass co- and injury. These normal glia functions are kept by nor- verslips in a total volume of 3 ml growth medium. Ali- mal activity of neurons [19]. The immune status of the quots of 5 × 106 nigrosine-excluding cells were plated in CNS is strictly regulated in healthy brain in which the 75 cm2 culture flasks. The cultures were incubated at immune response is kept to a minimum by activity of 37˚C in a humidified atmosphere of 5% CO2 in air. After neurons. Loss of neurons or their physiological activity 3 days of incubation the growth medium was removed, would render the CNS recognizable by invading immune the cell debris and non-attached cells were washed off cells and can sometimes result in a more severe neuro- and fresh medium was added and was changed every 2 - inflammatory cycle that promotes neurodegenerative di- 3 days. After 10 days some culture plates were incubated seases [20]. for 5 days and culture flasks for 2 and 8 days in medium TNF-α, a potent proinflammatory molecule, is mainly to which 200 international units (U)/ml of TNF-α (Sigma, produced by astrocytes in the CNS. During brain injury St. Louis, MO) had been added. The new medium was or inflammatory processes TNF-α is produced by acti- also changed every 2 - 3 days. vated microglia, astrocytes and macrophages [17,21]. In culture, astrocytes secret TNF at low level but the secre- 2.2. Neuronal Cultures tion is increased after treatment with inflammatory sti- muli such as interferon-gamma combined with IL-1beta. The cerebral neuronal cultures were prepared according TNF-α promotes the proliferation of astroglia and mi- to the method of [25]. The outer parts of the brain of croglia and therefore may be involved in pathological embryonic mice foetuses (E 15) were used. The cells of processes such as astrogliosis and demyelination [22]. the brains were separated in 0.25% trypsin in Puck’s TNF-α triggers downstream signaling cascades that con- solution for 5 min. at room temperature. Horse serum trol a number of cellular processes related to cell viabi- was added to stop the trypsin action, and the tissue was lity, gene expression, ion homostasis and synaptic inte- triturated by pipetting up and down. The suspensions grity [23]. It should be indicated that there is limited were centrifuged at 1000 rpm for 5 min. After removal of information available on the effect of TNF-α on astro- supernatant, the cells were resuspended in mMEM con- cytes-cortical neurons interactions. It is our hypothesis taining 30 mili-moles (mM) glucose and filtered through that inflammatory cytokines act upon astrocytes to alter a sterile 75 µm Nitex mesh. For culturing 5 × 104 nigro- their biochemical and physical properties, which may in sine-excluding cells were plated in 60 mm Petri dishes turn be responsible for the failure of neuronal regenera- containing 22 × 22 mm glass coverslips coated with tion. We have therefore examined the effect of TNF-α on poly-L-lysine (Sigma) in a total volume of 3 ml growth the ability of astrocytes to support the survival of the medium. After incubation in serum-free medium for 15 neurons and the growth of the neurites in mixed neuron- min. at 37˚C, the culture was rinsed once with fresh astrocyte cultures. The latter provides a valuable in vitro medium and incubated in freshly prepared medium model system for studying the direct interactions be- containing 5% hourse serum and 30 mili-moles (mM) tween neurons and astrocytes. glucose, with changes of medium every 2 - 3 days.
Load more

Recommended publications
  • Magnetic Resonance Imaging of Multiple Sclerosis: a Study of Pulse-Technique Efficacy
    691 Magnetic Resonance Imaging of Multiple Sclerosis: A Study of Pulse-Technique Efficacy Val M. Runge1 Forty-two patients with the clinical diagnosis of multiple sclerosis were examined by Ann C. Price1 proton magnetic resonance imaging (MRI) at 0.5 T. An extensive protocol was used to Howard S. Kirshner2 facilitate a comparison of the efficacy of different pulse techniques. Results were also Joseph H. Allen 1 compared in 39 cases with high-resolution x-ray computed tomography (CT). MRI revealed characteristic abnormalities in each case, whereas CT was positive in only 15 C. Leon Partain 1 of 33 patients. Milder grades 1 and 2 disease were usually undetected by CT, and in all A. Everette James, Jr.1 cases, the abnormalities noted on MRI were much more extensive than on CT. Cerebral abnormalities were best shown with the T2-weighted spin-echo sequence (TE/TR = 120/1000); brainstem lesions were best defined on the inversion-recovery sequence (TE/TI/TR =30/400/1250). Increasing TE to 120 msec and TR to 2000 msec heightened the contrast between normal and abnormal white matter. However, the signal intensity of cerebrospinal fluid with this pulse technique obscured some abnormalities. The diagnosis of multiple sclerosis continues to be a clinical challenge [1,2). The lack of an objective means of assessment further complicates the evaluation of treatment regimens. Evoked potentials, cerebrospinal fluid (CSF) analysis , and computed tomography (CT) are currently used for diagnosis, but all lack sensitivity and/or specificity. Furthermore, postmortem examinations demonstrate many more lesions than those suggested by clinical means [3).
    [Show full text]
  • Electrophysiological Changes That Accompany Reactive Gliosis in Vitro
    The Journal of Neuroscience, October 1, 1997, 17(19):7316–7329 Electrophysiological Changes That Accompany Reactive Gliosis In Vitro Stacey Nee MacFarlane and Harald Sontheimer Department of Neurobiology, University of Alabama, Birmingham, Birmingham, Alabama 35294 An in vitro injury model was used to examine the electrophys- negative resting potentials in nonproliferating (260 mV) versus iological changes that accompany reactive gliosis. Mechanical proliferating astrocytes (253 mV; p 5 0.015). Although 45% of scarring of confluent spinal cord astrocytes led to a threefold the nonproliferating astrocytes expressed Na 1 currents (0.47 increase in the proliferation of scar-associated astrocytes, as pS/pF), the majority of proliferating cells expressed prominent judged by bromodeoxyuridine (BrdU) labeling. Whole-cell Na 1 currents (0.94 pS/pF). Injury-induced electrophysiological patch-clamp recordings demonstrated that current profiles dif- changes are rapid and transient, appearing within 4 hr postin- 2 fered absolutely between nonproliferating (BrdU ) and prolifer- jury and, with the exception of KIR , returning to control con- ating (BrdU 1) astrocytes. The predominant current type ex- ductances within 24 hr. These differences between proliferating pressed in BrdU 2 cells was an inwardly rectifying K 1 current and nonproliferating astrocytes are reminiscent of electrophys- 2 (KIR ; 1.3 pS/pF). BrdU cells also expressed transient outward iological changes observed during gliogenesis, suggesting that K 1 currents, accounting for less than
    [Show full text]
  • Müller Glia Regenerative Potential Is Maintained Throughout Life Despite 2 Neurodegeneration and Gliosis in the Ageing Zebrafish Retina 3 4 AUTHORS 5 Raquel R
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.28.174821; this version posted October 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Müller Glia regenerative potential is maintained throughout life despite 2 neurodegeneration and gliosis in the ageing zebrafish retina 3 4 AUTHORS 5 Raquel R. Martins1,2, Mazen Zamzam3, Mariya Moosajee4,5,6,7, Ryan Thummel3, Catarina M. 6 Henriques1,2§, Ryan B. MaCDonald4§ 7 8 Affiliations: 9 1. Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK. 10 2. Department of OnCology and Metabolism, University of Sheffield, Sheffield, S10 2TN 11 UK. 12 3. Department of Ophthalmology, Visual and AnatomiCal SCienCes, Wayne State 13 University School of MediCine, Detroit, MI 48201, USA. 14 4. Institute of Ophthalmology, University College London, London, EC1V 9EL, UK. 15 5. Moorfields Eye Hospital NHS Foundation Trust, London, EC1V 2PD, UK 16 6. Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 17 3JH, UK 18 7. The FranCis CriCk Institute, London, NW1 1AT, London 19 20 21 22 §Co-corresponding authors: [email protected] and [email protected] 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.28.174821; this version posted October 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 25 ABSTRACT 26 Ageing is a signifiCant risk faCtor for degeneration of the retina.
    [Show full text]
  • Glial Cell Dysfunction in C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
    cells Review Glial Cell Dysfunction in C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Mehdi Ghasemi * , Kiandokht Keyhanian and Catherine Douthwright Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; [email protected] (K.K.); [email protected] (C.D.) * Correspondence: [email protected]; Tel.: +1-774-441-7726; Fax: +1-508-856-4485 Abstract: Since the discovery of the chromosome 9 open reading frame 72 (C9orf72) repeat expansion mutation in 2011 as the most common genetic abnormality in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) and frontotemporal dementia (FTD), progress in understanding the signaling pathways related to this mutation can only be described as intriguing. Two major theories have been suggested—(i) loss of function or haploinsufficiency and (ii) toxic gain of function from either C9orf72 repeat RNA or dipeptide repeat proteins (DPRs) generated from repeat-associated non-ATG (RAN) translation. Each theory has provided various signaling pathways that potentially participate in the disease progression. Dysregulation of the immune system, particularly glial cell dysfunction (mainly microglia and astrocytes), is demonstrated to play a pivotal role in both loss and gain of function theories of C9orf72 pathogenesis. In this review, we discuss the pathogenic roles of glial cells in C9orf72 ALS/FTD as evidenced by pre-clinical and clinical studies showing the presence of gliosis in C9orf72 ALS/FTD, pathologic hallmarks in glial cells, including TAR DNA-binding protein 43 (TDP-43) and p62 aggregates, and toxicity of C9orf72 glial cells. A better understanding of these pathways can provide new insights into the development of therapies targeting glial cell Citation: Ghasemi, M.; Keyhanian, abnormalities in C9orf72 ALS/FTD.
    [Show full text]
  • Single-Nucleus RNA-Seq Identifies Huntington Disease Astrocyte States Osama Al-Dalahmah1, Alexander A
    Al-Dalahmah et al. Acta Neuropathologica Communications (2020) 8:19 https://doi.org/10.1186/s40478-020-0880-6 RESEARCH Open Access Single-nucleus RNA-seq identifies Huntington disease astrocyte states Osama Al-Dalahmah1, Alexander A. Sosunov2, A. Shaik3, Kenneth Ofori1, Yang Liu1, Jean Paul Vonsattel1, Istvan Adorjan4, Vilas Menon5 and James E. Goldman1* Abstract Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated glial fibrillary acidic protein (GFAP) and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease.
    [Show full text]
  • REGULATION of GLIOSIS in the MOUSE RETINA a Dissertation
    REGULATION OF GLIOSIS IN THE MOUSE RETINA A Dissertation Submitted to the Faculty of Purdue University by Subramanian Dharmarajan In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2017 Purdue University Indianapolis, Indiana ii THE PURDUE UNIVERSITY GRADUATE SCHOOL STATEMENT OF COMMITTEE APPROVAL Dr. Teri Belecky-Adams Department of Biology Dr. Jason S. Meyer Department of Biology Dr. Stephen Randall Department of Biology Dr. AJ Baucum Department of Biology Dr. Yuk Fai Leung Department of Biological Sciences Approved by: Dr. Theodore R. Cummins Head of the Graduate Program iii To my wife Akshaya and my daughter Ananya. iv ACKNOWLEDGMENTS I would like to thank my advisor, Dr. Teri Belecky-Adams, for all of her support, encouragement and mentorship. You have helped me become the researcher I am today. In addition to my advisor, I would also like to thank my committee members Dr. AJ Baucum, Dr. Yuk Fei Leung, Dr. Jason Meyer and Dr. Stephen Randall. I appreciate your insightful comments and assistance throughout my project which have helped develop my skills. To my fellow graduate students and staff of the department of Biology, I would like to thank you for lending a helping hand whenever I needed it. I would like to also thank the faculty of the department of Biology for all their help with my projects and career advise. I am grateful to my friends Nilesh, Chetan, Rishi, Shrikant and Amrit. The game nights, dinners, road trips and general help and friendship helped me feel at home and was a welcome distraction from my lab work.
    [Show full text]
  • Dynamic Metabolic Patterns Tracking Neurodegeneration and Gliosis
    www.nature.com/scientificreports OPEN Dynamic metabolic patterns tracking neurodegeneration and gliosis following 26S proteasome Received: 30 November 2017 Accepted: 2 March 2018 dysfunction in mouse forebrain Published: xx xx xxxx neurons Philippine C. Geiszler1,2, Aslihan Ugun-Klusek3, Karen Lawler4, Marie-Christine Pardon4, Ding Yuchun5, Li Bai6, Clare A. Daykin2,7, Dorothee P. Auer1,8 & Lynn Bedford4 Metabolite profling is an important tool that may better capture the multiple features of neurodegeneration. With the considerable parallels between mouse and human metabolism, the use of metabolomics in mouse models with neurodegenerative pathology provides mechanistic insight and ready translation into aspects of human disease. Using 400 MHz nuclear magnetic resonance spectroscopy we have carried out a temporal region-specifc investigation of the metabolome of neuron-specifc 26S proteasome knockout mice characterised by progressive neurodegeneration and Lewy-like inclusion formation in the forebrain. An early signifcant decrease in N-acetyl aspartate revealed evidence of neuronal dysfunction before cell death that may be associated with changes in brain neuroenergetics, underpinning the use of this metabolite to track neuronal health. Importantly, we show early and extensive activation of astrocytes and microglia in response to targeted neuronal dysfunction in this context, but only late changes in myo-inositol; the best established glial cell marker in magnetic resonance spectroscopy studies, supporting recent evidence that additional early neuroinfammatory markers are needed. Our results extend the limited understanding of metabolite changes associated with gliosis and provide evidence that changes in glutamate homeostasis and lactate may correlate with astrocyte activation and have biomarker potential for tracking neuroinfammation. Neurodegenerative diseases such as Alzheimer’s disease (AD) are complex and the underlying mechanisms involved unclear.
    [Show full text]
  • Brain Engraftment of Autologous Macrophages Transduced with a Lentiviral flap Vector: an Approach to Complement Brain Dysfunctions
    Gene Therapy (2002) 9, 46–52 2002 Nature Publishing Group All rights reserved 0969-7128/02 $25.00 www.nature.com/gt RESEARCH ARTICLE Brain engraftment of autologous macrophages transduced with a lentiviral flap vector: an approach to complement brain dysfunctions E Mordelet1, K Kissa2, C-F Calvo3, M Lebastard4, G Milon4, S van der Werf1, C Vidal1 and P Charneau5 1Unite de Genetique Moleculaire des Virus Respiratoires, Institut Pasteur, Paris, France; 2Unite d’Embryologie Moleculaire, Institut Pasteur, Paris, France; 3INSERM U114, College de France, Paris, France; 4Unite d’Immunophysiologie et de Parasitisme Intracellulaire, Institut Pasteur, Paris, France; and 5Groupe de Virologie Moleculaire et Vectorologie, Institut Pasteur, Paris, France Transplantation of ex vivo gene-corrected autologous cells expression remained stable for 1 month without cytopathic represents an attractive therapeutic approach for brain dis- effect. In vivo, transplants of transduced macrophages into eases. Among the cells of the central nervous system, brain the striatum of adult rats exhibited long-term expression of macrophages are promising candidates due to their role in GFP up to 3 months. Transduced macrophages were tissue homeostasis and their implication in several neuro- observed around the brain injection site and exhibited the logical diseases. Up to now, gene transfer into macrophages brain macrophage/microglia phenotype. There was no sig- has proven difficult by most currently available gene delivery nificant sign of astrogliosis around the graft. These results methods. We describe herein, an efficient transduction of rat confirm the potential of lentiviral vectors for efficient and bone marrow-derived and brain macrophages with an HIV- stable ex vivo transduction of macrophages.
    [Show full text]
  • Key Targets for Treating Central Sensitization in Chronic Pain Patients?
    Expert Opinion on Therapeutic Targets ISSN: 1472-8222 (Print) 1744-7631 (Online) Journal homepage: http://www.tandfonline.com/loi/iett20 Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients? Jo Nijs, Marco L. Loggia, Andrea Polli, Maarten Moens, Eva Huysmans, Lisa Goudman, Mira Meeus, Luc Vanderweeën, Kelly Ickmans & Daniel Clauw To cite this article: Jo Nijs, Marco L. Loggia, Andrea Polli, Maarten Moens, Eva Huysmans, Lisa Goudman, Mira Meeus, Luc Vanderweeën, Kelly Ickmans & Daniel Clauw (2017) Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?, Expert Opinion on Therapeutic Targets, 21:8, 817-826, DOI: 10.1080/14728222.2017.1353603 To link to this article: http://dx.doi.org/10.1080/14728222.2017.1353603 Accepted author version posted online: 07 Jul 2017. Published online: 12 Jul 2017. Submit your article to this journal Article views: 80 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iett20 Download by: [173.48.111.165] Date: 27 July 2017, At: 04:29 EXPERT OPINION ON THERAPEUTIC TARGETS, 2017 VOL. 21, NO. 8, 817–826 https://doi.org/10.1080/14728222.2017.1353603 REVIEW Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients? Jo Nijsa,b,c, Marco L. Loggiaj, Andrea Pollia,b, Maarten Moensd,e,
    [Show full text]
  • Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-␥
    The Journal of Neuroscience, May 15, 1997, 17(10):3664–3674 Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-g Maria Rostworowski,1 Vijayabalan Balasingam,1 Sophie Chabot,1,2 Trevor Owens,1 and Voon Wee Yong1,2 1Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada, and 2Neuroscience Research Group, University of Calgary, Calgary NW, Alberta T2N 4N1, Canada The relevance of astrogliosis remains controversial, espe- We determined whether endogenous interferon (IFN)-g could cially with respect to the beneficial or detrimental influence of be responsible for the observed increases in IL-1 and TNF-a, reactive astrocytes on CNS recovery. This dichotomy can be because IFN-g is a potent microglia/macrophage activator, resolved if the mediators of astrogliosis are identified. We and because its exogenous administration to rodents en- have measured the levels of transcripts encoding inflamma- hanced astrogliosis after adult or neonatal insults. A lack of tory cytokines in injury systems in which the presence or requirement for endogenous IFN-g was demonstrated by absence of astrogliosis could be produced selectively. A three lines of evidence. First, no increase in IFN-g transcripts stab injury to the adult mouse brain using a piece of nitro- could be found at injury. Second, the administration of a cellulose (NC) membrane elicited a prompt and marked in- neutralizing antibody to IFN-g did not attenuate astrogliosis. crease in levels of transcripts for interleukin (IL)-1a, IL-1b, Third, in IFN-g knockout adult mice, astrogliosis and in- and tumor necrosis factor (TNF)-a, which are considered to creases in levels of IL-1a and TNF-a were induced rapidly by be microglia/macrophage cytokines.
    [Show full text]
  • Pathological Changes of Astrocytes Under Seizure Shanshan Lu1, Fushun Wang1,2,3* and Jason H
    Lu, et al. Int J Brain Disord Treat 2016, 2:008 Volume 2 | Issue 1 International Journal of ISSN: 2469-5866 Brain Disorders and Treatment Review Article: Open Access Pathological Changes of Astrocytes under Seizure Shanshan Lu1, Fushun Wang1,2,3* and Jason H. Huang3* 1Department of Psychology, Nanjing University of Chinese Medicine, China 2Department of Neurosurgery, University of Rochester, USA 3Department of Neurosurgery, Baylor Scott & White Health, USA *Corresponding author: Fushun Wang and Jason H. Huang, Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas 76508, USA, E-mail: [email protected], [email protected] [9,10]. Current research has expanded their function to important Abstract homeostatic and neuronal modulatory functions [11]. Astrocytes Multiple lines of studies support the view that defective functions are involved in regulating ion homeostasis, maintenance of the of astrocytes contribute to neuronal hyper-excitability in the blood brain barrier (BBB) function, metabolism of amino acid epileptic brain. Autopsy and surgical resection specimens find that neurotransmitter, as well as nutrient and energy support for neurons post-traumatic seizures and chronic temporal lobe epilepsy may [12]. Our recent reports demonstrated that astrocytes could actively originate from glial scars. Astrogliosis, a component of glial scar, 2+ which involves structural and metabolic changes in astrocytes, is regulate these processes with intracellular Ca wave regulated often a prominent feature of temporal epilepsy and most animal signaling pathways [13,14]. The present review summarized the models of recurrent seizures. Although glial scar formation has been roles of reactive astrocytes in the development and progression of recognized for over 120 years, fundamental aspects of the cellular epileptic seizures, and discussed the relevance of calcium signaling in mechanisms are poorly understood.
    [Show full text]
  • Tumor Necrosis Factor Inhibition Attenuates White Matter Gliosis After Systemic Inflammation in Preterm Fetal Sheep Robert Galinsky1,2,3, Simerdeep K
    Galinsky et al. Journal of Neuroinflammation (2020) 17:92 https://doi.org/10.1186/s12974-020-01769-6 RESEARCH Open Access Tumor necrosis factor inhibition attenuates white matter gliosis after systemic inflammation in preterm fetal sheep Robert Galinsky1,2,3, Simerdeep K. Dhillon1, Justin M. Dean1, Joanne O. Davidson1, Christopher A. Lear1, Guido Wassink1, Fraser Nott2, Sharmony B. Kelly2, Mhoyra Fraser1, Caroline Yuill1, Laura Bennet1 and Alistair Jan Gunn1* Abstract Background: Increased circulating levels of tumor necrosis factor (TNF) are associated with greater risk of impaired neurodevelopment after preterm birth. In this study, we tested the hypothesis that systemic TNF inhibition, using the soluble TNF receptor Etanercept, would attenuate neuroinflammation in preterm fetal sheep exposed to lipopolysaccharide (LPS). Methods: Chronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive saline (control; n = 7), LPS infusion (100 ng/kg i.v. over 24 h then 250 ng/kg/24 h for 96 h plus 1 μg LPS boluses at 48, 72, and 96 h, to induce inflammation; n = 8) or LPS plus two i.v. infusions of Etanercept (2 doses, 5 mg/kg infused over 30 min, 48 h apart) started immediately before LPS-exposure (n = 8). Sheep were killed 10 days after starting infusions, for histology. Results: LPS boluses were associated with increased circulating TNF, interleukin (IL)-6 and IL-10, electroencephalogram (EEG) suppression, hypotension, tachycardia, and increased carotid artery perfusion (P < 0.05 vs. control). In the periventricular and intragyral white matter, LPS exposure increased gliosis, TNF- positive cells, total oligodendrocytes, and cell proliferation (P < 0.05 vs control), but did not affect myelin expression or numbers of neurons in the cortex and subcortical regions.
    [Show full text]