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The role of PPAR activation during the systemic response to brain injury
BACKGROUND: Fenofibrate, a PPAR-α activator, has shown promising results as a neuroprotective therapy, with proposed anti-inflammatory and anti-oxidant effects. However, it displays poor blood-brain barrier permeability leading to some ambiguity over its mechanism of action. Experimentally induced b...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450490/ https://www.ncbi.nlm.nih.gov/pubmed/25994490 http://dx.doi.org/10.1186/s12974-015-0295-7 |
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author | Losey, Patrick Ladds, Emma Laprais, Maud Geuvel, Borna Burns, Laura Bordet, Regis Anthony, Daniel C |
author_facet | Losey, Patrick Ladds, Emma Laprais, Maud Geuvel, Borna Burns, Laura Bordet, Regis Anthony, Daniel C |
author_sort | Losey, Patrick |
collection | PubMed |
description | BACKGROUND: Fenofibrate, a PPAR-α activator, has shown promising results as a neuroprotective therapy, with proposed anti-inflammatory and anti-oxidant effects. However, it displays poor blood-brain barrier permeability leading to some ambiguity over its mechanism of action. Experimentally induced brain injury has been shown to elicit a hepatic acute phase response that modulates leukocyte recruitment to the injured brain. Here, we sought to discover whether one effect of fenofibrate might include the suppression of the acute phase response (APR) following brain injury. METHODS: A 1-h intraluminal thread middle cerebral artery occlusion (MCAO) model followed by a 6-h reperfusion was performed in C57/BL6 mice. Quantitative reverse transcriptase-polymerase chain reaction was then used to measure hepatic expression of chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine ligand 10 (CXCL10) and serum amyloid A-1 (SAA-1), and immunohistochemical analysis was used to quantify brain and hepatic neutrophil infiltration following stroke. RESULTS: The MCAO and sham surgery induced the expression of all three acute phase reactants. A 14-day fenofibrate pre-treatment decreased reactant production, infarct volume, and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. CONCLUSIONS: The data highlight a novel mechanism of action for fenofibrate and lend further evidence towards the promotion of its use as a prophylactic therapy in patients at risk of cerebral ischaemia. Further research is required to elucidate the mechanistic explanation underlying its actions. |
format | Online Article Text |
id | pubmed-4450490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44504902015-06-02 The role of PPAR activation during the systemic response to brain injury Losey, Patrick Ladds, Emma Laprais, Maud Geuvel, Borna Burns, Laura Bordet, Regis Anthony, Daniel C J Neuroinflammation Research BACKGROUND: Fenofibrate, a PPAR-α activator, has shown promising results as a neuroprotective therapy, with proposed anti-inflammatory and anti-oxidant effects. However, it displays poor blood-brain barrier permeability leading to some ambiguity over its mechanism of action. Experimentally induced brain injury has been shown to elicit a hepatic acute phase response that modulates leukocyte recruitment to the injured brain. Here, we sought to discover whether one effect of fenofibrate might include the suppression of the acute phase response (APR) following brain injury. METHODS: A 1-h intraluminal thread middle cerebral artery occlusion (MCAO) model followed by a 6-h reperfusion was performed in C57/BL6 mice. Quantitative reverse transcriptase-polymerase chain reaction was then used to measure hepatic expression of chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine ligand 10 (CXCL10) and serum amyloid A-1 (SAA-1), and immunohistochemical analysis was used to quantify brain and hepatic neutrophil infiltration following stroke. RESULTS: The MCAO and sham surgery induced the expression of all three acute phase reactants. A 14-day fenofibrate pre-treatment decreased reactant production, infarct volume, and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. CONCLUSIONS: The data highlight a novel mechanism of action for fenofibrate and lend further evidence towards the promotion of its use as a prophylactic therapy in patients at risk of cerebral ischaemia. Further research is required to elucidate the mechanistic explanation underlying its actions. BioMed Central 2015-05-22 /pmc/articles/PMC4450490/ /pubmed/25994490 http://dx.doi.org/10.1186/s12974-015-0295-7 Text en © Losey et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Losey, Patrick Ladds, Emma Laprais, Maud Geuvel, Borna Burns, Laura Bordet, Regis Anthony, Daniel C The role of PPAR activation during the systemic response to brain injury |
title | The role of PPAR activation during the systemic response to brain injury |
title_full | The role of PPAR activation during the systemic response to brain injury |
title_fullStr | The role of PPAR activation during the systemic response to brain injury |
title_full_unstemmed | The role of PPAR activation during the systemic response to brain injury |
title_short | The role of PPAR activation during the systemic response to brain injury |
title_sort | role of ppar activation during the systemic response to brain injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450490/ https://www.ncbi.nlm.nih.gov/pubmed/25994490 http://dx.doi.org/10.1186/s12974-015-0295-7 |
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