Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor -deficient mice

Details

Serval ID
serval:BIB_62E64D7E098A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor -deficient mice
Journal
Journal of Cerebral Blood Flow and Metabolism
Author(s)
Arsenijevic Denis, Bilbao Fabienne de, Plamondon Julie, Paradis Eric, Vallet Philippe, Richard Denis, Langhans Wolfgang, Giannakopoulos Panteleimon
ISSN
0271-678X
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
26
Number
3
Pages
433-445
Language
english
Notes
SAPHIRID:61380
Abstract
Peroxisome proliferator-activated receptors (PPARs) are involved in energy expenditure, regulation of inflammatory processes, and cellular protection in peripheral tissues. Among the different types of PPARs, PPARbeta is the only one to be widely expressed in cortical neurons. Using PPARbeta knockout (KO) mice, we report here a detailed investigation of the role of PPARbeta in cerebral ischemic damage, associated inflammatory and antioxidant processes as well as food intake regulation after middle cerebral artery occlusion (MCAO). The PPARbeta KO mice had a two-fold increase in infarct size compared with wild-type (WT) mice. Brain oxidative stress was dramatically enhanced in these KO mice, as documented by an increased content of malondialdehyde, decreased levels of glutathione and manganese superoxide dismutase, and no induction of uncoupling protein 2 (UCP2) mRNA. Unlike WT mice, PPARbeta KO mice showed a marked increase of prooxidant interferon-gamma but no induction of nerve growth factor and tumor necrosis factor alpha after MCAO. In WT mice, MCAO resulted in inflammation-specific transient hyperphagia from day 3 to day 5 after ischemia, which was associated with an increase in neuropeptide Y (NPY) mRNA. This hyperphagic phase and NPY mRNA induction were not observed in PPARbeta KO mice. Furthermore, our study also suggests for the first time that UCP2 is involved in MCAO food intake response. These data indicate that PPARbeta plays an important role in integrating and regulating central inflammation, antioxidant mechanisms, and food intake after MCAO, and suggest that the use of PPARbeta agonists may be of interest for the prevention of central ischemic damage
Pubmed
Web of science
Create date
10/03/2008 11:04
Last modification date
20/08/2019 14:19
Usage data