Pyruvate protects against experimental stroke via an anti-inflammatory mechanism.
Pyruvate, a key intermediate in glucose metabolism, was explored as a potential treatment in models of experimental stroke and inflammation. Pyruvate was administered to rodents after the onset of middle cerebral artery occlusion (MCAO). Since the extent of inflammation is often proportional to the size of the infarct, we also studied a group of animals given lipopolysaccharide (LPS) to cause brain inflammation without cell death. Following MCAO, pyruvate did not affect physiological parameters but significantly reduced infarct volume, improved behavioral tests and reduced numbers of neutrophils, microglial and NFkappaB activation. Animals given LPS showed increased microglial and NFkappaB activation which was almost completely abolished by pyruvate. Lactate, a major metabolite of pyruvate, was increased after pyruvate administration. However, administration of lactate itself did not have any anti-inflammatory effects. Pyruvate protects against ischemia possibly by blocking inflammation, but lactate itself does not appear to explain pyruvate's anti-inflammatory properties.
Wang
Qing
Q
Department of Neurology, University of California, San Francisco and Veterans Affairs Medical Center, CA 94121, USA.
van Hoecke
Michael
M
Tang
Xian Nan
XN
Lee
Hokyou
H
Zheng
Zheng
Z
Swanson
Raymond A
RA
Yenari
Midori A
MA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D004660:Encephalitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D000097782:NF-kappaB-Inducing Kinase
D053331:Ectodysplasins; D019344:Lactic Acid; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9; D017346:Protein Serine-Threonine Kinases; D019289:Pyruvic Acid; D013778:Tetrazolium Salts; D000097782:NF-kappaB-Inducing Kinase; C009591:triphenyltetrazolium