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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Li, Jay-Shake / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

IMPACT FACTOR 2018: 2.157
5-year IMPACT FACTOR: 2.935

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 0.980
Source Normalized Impact per Paper (SNIP) 2017: 0.804

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Volume 24, Issue 1


Multiple sclerosis and glutamate excitotoxicity

Milos Kostic / Nikola Zivkovic / Ivana Stojanovic
Published Online: 2012-11-12 | DOI: https://doi.org/10.1515/revneuro-2012-0062


The previous understanding of multiple sclerosis was solely related to neuroinflammation and its harmful effects; however, countless data indicate the importance of some inflammation-independent, neurodegenerative mechanisms associated with mitochondria malfunction, iron deposition and oxidative stress. Recently, it has been postulated that glutamate excitotoxicity, a phenomenon that takes place when an excessive amount of glutamate overactivates its cellular receptors and induces cell death, could be a missing link between inflammatory and neurodegenerative processes evident in multiple sclerosis. Glutamate is the major excitatory neurotransmitter of the central nervous system, which has been proven to have a central role in a complex communication network established between all residential brain cells, including neurons, astrocytes, oligodendrocytes and microglia. Thus, the disturbance of glutamate homeostasis could affect practically all physiological functions and interactions of brain cells, leading to heterogeneity of pathological events. The understanding of glutamate excitotoxicity as a valid mechanism of central nervous system damage in multiple sclerosis, requires the revision of the current knowledge about a source of elevated extracellular glutamate, glutamate receptor alterations, alterations of glutamate transporters and metabolizing enzymes, as well as molecular mechanism of excitotoxic damage.

Keywords: axonal degeneration; demyelination; glutamate metabolizing enzymes; glutamate receptors; glutamate transporters

About the article

Milos Kostic

Dr. Milos S. Kostic, currently a PhD student, is working as a teaching assistant at the Department of Immunology, Faculty of Medicine, University of Nis. His ongoing PhD thesis explores Th immunological profile of patients suffering from multiple sclerosis and its repercussion on neurodegenerative processes in the form of axonal degeneration. Major scientific interest is Th17 polarized environment in encephalic compartment and its association with glutamate excitotoxicity.

Nikola Zivkovic

Dr. Nikola D. Zivkovic is employed as a teaching assistant at the Department of Pathology, Faculty of Medicine, University of Nis. Currently a PhD student, engaged in research in the field of immunoproliferative diseases. His special interest is head and neck pathology with focus on disorders of immune system in this region.

Ivana Stojanovic

Prof. Dr. Ivana R. Stojanovic received a PhD in Biochemistry at University of Nis Faculty of Medicine on polyamine and nitric oxide metabolism interactions in seizures. The leader of the scientific subproject, exploring L-arginine metabolism and nitric oxide signalling in CNS inflammation and neurodegeneration. Her current scientific interests focus on the role of oxidative stress, nitrergicsignalling and excitotoxicity in multiple sclerosis pathogenetic mechanisms.

Corresponding author: Milos Kostic, Departement of Immunology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia

Received: 2012-08-02

Accepted: 2012-09-07

Published Online: 2012-11-12

Published in Print: 2013-02-01

Citation Information: Reviews in the Neurosciences, Volume 24, Issue 1, Pages 71–88, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2012-0062.

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