Systemic pyruvate administration markedly reduces infarcts and motor deficits in rat models of transient and permanent focal cerebral ischemia.

Abstract

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.

• Authors: Jung-Sun Yi, Tae-Youn Kim, Dong Kyu Kim, Jae-Young Koh
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 26 Issue 1 Pg. 94-104 (Apr 2007) ISSN: 0969-9961 [Print] United States
• PMID: 17261368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NAD
• Pyruvic Acid

Topics

• Animals
• Brain (pathology)
• Brain Chemistry (drug effects)
• Brain Ischemia (complications, pathology)
• Cell Death (drug effects)
• Cerebral Infarction (etiology, pathology, prevention & control)
• Dose-Response Relationship, Drug
• In Situ Nick-End Labeling
• Ischemic Attack, Transient (complications, pathology)
• Laser-Doppler Flowmetry
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Male
• NAD (metabolism)
• Psychomotor Performance (drug effects, physiology)
• Pyruvic Acid (therapeutic use)
• Rats
• Rats, Sprague-Dawley