Neuronal expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 15d-prostaglandin J2--mediated protection of brain after experimental cerebral ischemia in rat.
Existing experimental evidence suggests that PPARgamma may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPARgamma messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPARgamma mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPARgamma in neurons after ischemia. Intraventricular injection of 15d-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a proposed endogenous PPARgamma agonist, into the ischemic rat brains significantly increased the PPARgamma-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPARgamma up-regulation in response to ischemia may contribute to PPARgamma activation in the presence of PPARgamma agonists. Activation of PPARgamma in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury.
Ou
Zhishuo
Z
University of Texas Health Science Center-Houston, Medical School, Department of Neurology, Stroke Program, Houston, 77030, USA.
Zhao
Xiurong
X
Labiche
Lise A
LA
Strong
Roger
R
Grotta
James C
JC
Herrmann
Oliver
O
Aronowski
Jaroslaw
J
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
C477819:15-deoxyprostaglandin J2; D018696:Neuroprotective Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D015230:Prostaglandin D2