Systemic pyruvate administration markedly reduces infarcts and motor deficits in rat models of transient and permanent focal cerebral ischemia.
Pyruvate markedly reduces neuronal death following transient global ischemia. In the present study, we investigated the possible neuroprotective effect of pyruvate in focal ischemia. Pyruvate (62.5-250 mg/kg) treatment, regardless of whether given intraperitoneally (ip) or intravenously (iv), decreased infarct volume by more than 50% in both transient (1 h) and permanent occlusion models. The infarct-reducing effects of pyruvate were maintained 14 days (d) after MCAO. Interestingly, higher doses failed to reduce the infarct size. Pyruvate administration also reduced motor deficits. Magnetic resonance (MR) spectroscopy revealed that protective doses of pyruvate, but not the non-protective doses, were associated with a reduction in the level of lactate compared with saline controls. Diffusion-weighted MR images further confirmed infarct reduction in pyruvate-treated rats. Pyruvate is an endogenous metabolite of glycolysis, and hence is unlikely to have serious side effects. Considering its substantial neuroprotective capacity in focal cerebral ischemia, a clinical trial is warranted.
Yi
Jung-Sun
JS
Neural Injury Research Lab, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
Kim
Tae-Youn
TY
Kyu Kim
Dong
D
Koh
Jae-Young
JY
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002544:Cerebral Infarction / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009243:NAD / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D019289:Pyruvic Acid / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D019289:Pyruvic Acid