Friday, 18 May 2001, 12:00 - 12:10
INCREASE IN BRAIN ANTI-OXIDANT ENZYMES AS A POTENTIAL MECHANISM OF BRAIN
ISCHEMIC TOLERANCE INDUCED BY THE PPAR-ALPHA ACTIVATOR FENOFIBRATE.
Author/-s: D. Deplanque, P. Gelé, I. Six, J. C. Fruchart, P. Duriez, R. Bordet (France)
Faculty of Medicine
In a previous study,* we demonstrated that the Peroxisome Proliferator-Activated Receptor alpha (PPAR-alpha)
activator, fenofibrate, suppresses susceptibility to focal cerebral ischemia in Apolipoprotein E-deficient mice
independently of lipid metabolism. The aim of this study was to evaluate whether a pretreatment with
fenofibrate could reduce cerebral infarct volume in Wild-type mice and increase brain anti-oxidant enzyme
activities, which are potential mediators of brain ischemic tolerance. A one-hour ischemia was performed in
C57/black mice after a 2 weeks treatment period with a diet containing 0.2% fenofibrate (F, n=6) or placebo (P,
n=6). After 24 hours of cerebral reperfusion, mice were sacrificed to permit infarct volume quantification. During
the same period, other mice were receiving fenofibrate (n=5) or placebo (n=7) before performing measurement
of brain anti-oxidant enzyme activities. Fenofibrate significantly reduced cerebral infarct volumes (F: 34 ± 4
mm3 versus P: 50 ± 4 mm3 ; p=0.02), particularly in the cortex area (F: 20 ± 3 mm3 versus P: 36 ± 2 mm3 ;
p<0.01). Concurrently, mice treated with fenofibrate had a significant increase in brain activity of Cu/Zn
superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione S transferase without
change in catalase and Mn superoxide dismutase activities. These data show that a PPAR-alpha activator could
induce brain ischemic tolerance in mice, in part through an increase of brain anti-oxidant enzyme activities.
* Deplanque et al. Circulation 1999 ; 100 (Suppl I) : I 36.
eurostroke.org
(thanks to Mike M. for the meeting link) |
