Inhibition of the Cerebral Ischemic Injury by Ethyl Pyruvate With a Wide Therapeutic Window

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Abstract
Background and Purpose— Ethyl pyruvate (EP) is a pyruvate derivative that has been reported recently to prevent lethality in mice with established lethal sepsis and systemic inflammation. In this study, we examined the neuroprotective effect of EP in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO). Methods— Male Sprague-Dawley rats were subjected to 1 hour of MCAO, and EP was administered at various time points before or after MCAO. The changes in the brain infarction, neurological deficits, microglia activation, and proinflammatory cytokine expression were evaluated. BV2 microglial cells were also used to access the anti-inflammatory effect of EP. Results— The administration of EP intraperitoneally at 30 minutes before or at 4 or 12 hours after MCAO reduced the infarct volume to 10.3±3.4% (n=6; PPPPConclusions— These results suggest that EP affords the strong protection of the delayed cerebral ischemic injury with a wide therapeutic window.