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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.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.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.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.

Original publication

DOI

10.1186/s12974-015-0295-7

Type

Journal article

Journal

Journal of neuroinflammation

Publication Date

22/05/2015

Volume

12

Pages

99 - 99

Addresses

EA 1046, Pharmacology, Faculty of Medicine, Research Branch, IMPRT, University of Lille North of France, Place de Verdun, Lille, Cedex, 59045, France.

Keywords

Animals, Mice, Inbred C57BL, Mice, Rats, Rats, Wistar, Brain Injuries, Infarction, Middle Cerebral Artery, Disease Models, Animal, Serum Amyloid A Protein, Peroxisome Proliferator-Activated Receptors, RNA, Messenger, Neuroprotective Agents, Analysis of Variance, Neutrophil Infiltration, Male, Chemokine CXCL10, Chemokine CXCL1, Fenofibrate