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Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses

Food composition influences stroke risk, but its effects on ischemic injury and neurological deficits are poorly examined. While severe reduction of protein content was found to aggravate neurological impairment and brain injury as a consequence of combined energy-protein malnutrition, moderate prot...

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Autores principales: de Carvalho, Tayana Silva, Sanchez-Mendoza, Eduardo H., Nascentes, Luiza M., Schultz Moreira, Adriana R., Sardari, Maryam, Dzyubenko, Egor, Kleinschnitz, Christoph, Hermann, Dirk M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835038/
https://www.ncbi.nlm.nih.gov/pubmed/31257559
http://dx.doi.org/10.1007/s12035-019-01679-6
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author de Carvalho, Tayana Silva
Sanchez-Mendoza, Eduardo H.
Nascentes, Luiza M.
Schultz Moreira, Adriana R.
Sardari, Maryam
Dzyubenko, Egor
Kleinschnitz, Christoph
Hermann, Dirk M.
author_facet de Carvalho, Tayana Silva
Sanchez-Mendoza, Eduardo H.
Nascentes, Luiza M.
Schultz Moreira, Adriana R.
Sardari, Maryam
Dzyubenko, Egor
Kleinschnitz, Christoph
Hermann, Dirk M.
author_sort de Carvalho, Tayana Silva
collection PubMed
description Food composition influences stroke risk, but its effects on ischemic injury and neurological deficits are poorly examined. While severe reduction of protein content was found to aggravate neurological impairment and brain injury as a consequence of combined energy-protein malnutrition, moderate protein restriction not resulting in energy deprivation was recently suggested to protect against perinatal hypoxia-ischemia. Male C57BL6/j mice were exposed to moderate protein restriction by providing a normocaloric diet containing 8% protein (control: 20% protein) for 7, 14, or 30 days. Intraluminal middle cerebral artery occlusion was then induced. Mice were sacrificed 24 h later. Irrespective of the duration of food modification (that is, 7–30 days), protein restriction reduced neurological impairment of ischemic mice revealed by a global and focal deficit score. Prolonged protein restriction over 30 days also reduced infarct volume, brain edema, and blood-brain barrier permeability and increased the survival of NeuN+ neurons in the core of the stroke (i.e., striatum). Neuroprotection by prolonged protein restriction went along with reduced brain infiltration of CD45+ leukocytes and reduced expression of inducible NO synthase and interleukin-1β. As potential mechanisms, increased levels of the NAD-dependent deacetylase sirtuin-1 and anti-oxidant glutathione peroxidase-3 were noted in ischemic brain tissue. Irrespective of the protein restriction duration, a shift from pro-oxidant oxidative stress markers (NADPH oxidase-4) to anti-oxidant markers (superoxide dismutase-1/2, glutathione peroxidase-3 and catalase) was found in the liver. Moderate protein restriction protects against ischemia in the adult brain. Accordingly, dietary modifications may be efficacious strategies promoting stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-019-01679-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-68350382019-11-20 Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses de Carvalho, Tayana Silva Sanchez-Mendoza, Eduardo H. Nascentes, Luiza M. Schultz Moreira, Adriana R. Sardari, Maryam Dzyubenko, Egor Kleinschnitz, Christoph Hermann, Dirk M. Mol Neurobiol Article Food composition influences stroke risk, but its effects on ischemic injury and neurological deficits are poorly examined. While severe reduction of protein content was found to aggravate neurological impairment and brain injury as a consequence of combined energy-protein malnutrition, moderate protein restriction not resulting in energy deprivation was recently suggested to protect against perinatal hypoxia-ischemia. Male C57BL6/j mice were exposed to moderate protein restriction by providing a normocaloric diet containing 8% protein (control: 20% protein) for 7, 14, or 30 days. Intraluminal middle cerebral artery occlusion was then induced. Mice were sacrificed 24 h later. Irrespective of the duration of food modification (that is, 7–30 days), protein restriction reduced neurological impairment of ischemic mice revealed by a global and focal deficit score. Prolonged protein restriction over 30 days also reduced infarct volume, brain edema, and blood-brain barrier permeability and increased the survival of NeuN+ neurons in the core of the stroke (i.e., striatum). Neuroprotection by prolonged protein restriction went along with reduced brain infiltration of CD45+ leukocytes and reduced expression of inducible NO synthase and interleukin-1β. As potential mechanisms, increased levels of the NAD-dependent deacetylase sirtuin-1 and anti-oxidant glutathione peroxidase-3 were noted in ischemic brain tissue. Irrespective of the protein restriction duration, a shift from pro-oxidant oxidative stress markers (NADPH oxidase-4) to anti-oxidant markers (superoxide dismutase-1/2, glutathione peroxidase-3 and catalase) was found in the liver. Moderate protein restriction protects against ischemia in the adult brain. Accordingly, dietary modifications may be efficacious strategies promoting stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-019-01679-6) contains supplementary material, which is available to authorized users. Springer US 2019-07-01 2019 /pmc/articles/PMC6835038/ /pubmed/31257559 http://dx.doi.org/10.1007/s12035-019-01679-6 Text en © The Author(s) 2019 Open Access This 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.
spellingShingle Article
de Carvalho, Tayana Silva
Sanchez-Mendoza, Eduardo H.
Nascentes, Luiza M.
Schultz Moreira, Adriana R.
Sardari, Maryam
Dzyubenko, Egor
Kleinschnitz, Christoph
Hermann, Dirk M.
Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title_full Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title_fullStr Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title_full_unstemmed Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title_short Moderate Protein Restriction Protects Against Focal Cerebral Ischemia in Mice by Mechanisms Involving Anti-inflammatory and Anti-oxidant Responses
title_sort moderate protein restriction protects against focal cerebral ischemia in mice by mechanisms involving anti-inflammatory and anti-oxidant responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835038/
https://www.ncbi.nlm.nih.gov/pubmed/31257559
http://dx.doi.org/10.1007/s12035-019-01679-6
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