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Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation
BACKGROUND: Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716243/ https://www.ncbi.nlm.nih.gov/pubmed/29202856 http://dx.doi.org/10.1186/s12974-017-1010-7 |
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author | Dhungana, Hiramani Huuskonen, Mikko T. Jaronen, Merja Lemarchant, Sighild Ali, Humair Keksa-Goldsteine, Velta Goldsteins, Gundars Kanninen, Katja M. Koistinaho, Jari Malm, Tarja |
author_facet | Dhungana, Hiramani Huuskonen, Mikko T. Jaronen, Merja Lemarchant, Sighild Ali, Humair Keksa-Goldsteine, Velta Goldsteins, Gundars Kanninen, Katja M. Koistinaho, Jari Malm, Tarja |
author_sort | Dhungana, Hiramani |
collection | PubMed |
description | BACKGROUND: Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage. METHODS: By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO). RESULTS: SSO significantly reduced the lipopolysaccharide/interferon-γ-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α, and the protein levels of inflammatory enzymes including nitric oxide synthase 2, cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in microglia, without causing cell toxicity. Although SSO failed to directly alleviate glutamate-induced excitotoxicity in murine cortical neurons, it prevented inflammation-induced neuronal death in microglia-neuron co-cultures. Importantly, oral administration of SSO in Balb/c mice subjected to permanent occlusion of the middle cerebral artery reduced microglial activation in the peri-ischemic area and attenuated brain damage. This in vivo neuroprotective effect of SSO was associated with a reduction in the COX-2 and heme oxygenase-1 immunoreactivities. CONCLUSIONS: Our results suggest that SSO is an anti-inflammatory and a possible therapeutic candidate in diseases such as stroke where inflammation is a central hallmark. |
format | Online Article Text |
id | pubmed-5716243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57162432017-12-08 Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation Dhungana, Hiramani Huuskonen, Mikko T. Jaronen, Merja Lemarchant, Sighild Ali, Humair Keksa-Goldsteine, Velta Goldsteins, Gundars Kanninen, Katja M. Koistinaho, Jari Malm, Tarja J Neuroinflammation Research BACKGROUND: Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage. METHODS: By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO). RESULTS: SSO significantly reduced the lipopolysaccharide/interferon-γ-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α, and the protein levels of inflammatory enzymes including nitric oxide synthase 2, cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in microglia, without causing cell toxicity. Although SSO failed to directly alleviate glutamate-induced excitotoxicity in murine cortical neurons, it prevented inflammation-induced neuronal death in microglia-neuron co-cultures. Importantly, oral administration of SSO in Balb/c mice subjected to permanent occlusion of the middle cerebral artery reduced microglial activation in the peri-ischemic area and attenuated brain damage. This in vivo neuroprotective effect of SSO was associated with a reduction in the COX-2 and heme oxygenase-1 immunoreactivities. CONCLUSIONS: Our results suggest that SSO is an anti-inflammatory and a possible therapeutic candidate in diseases such as stroke where inflammation is a central hallmark. BioMed Central 2017-12-04 /pmc/articles/PMC5716243/ /pubmed/29202856 http://dx.doi.org/10.1186/s12974-017-1010-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Dhungana, Hiramani Huuskonen, Mikko T. Jaronen, Merja Lemarchant, Sighild Ali, Humair Keksa-Goldsteine, Velta Goldsteins, Gundars Kanninen, Katja M. Koistinaho, Jari Malm, Tarja Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title | Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title_full | Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title_fullStr | Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title_full_unstemmed | Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title_short | Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
title_sort | sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716243/ https://www.ncbi.nlm.nih.gov/pubmed/29202856 http://dx.doi.org/10.1186/s12974-017-1010-7 |
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