Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats

TL;DR

This study investigated pyruvate's neuroprotective effects in a rat model of permanent ischemic stroke, finding limited benefits and some evidence of increased damage at higher doses, indicating different mechanisms in permanent versus transient ischemia.

Contribution

The paper provides new insights into the effects of pyruvate in permanent ischemic stroke, showing it does not confer significant neuroprotection and may even worsen outcomes at certain doses.

Findings

Lower doses reduced mortality and neurological deficits.

Higher doses increased cortical infarction.

Pyruvate's effects differ between permanent and transient ischemia.

Abstract

Recent experimental evidences indicate that pyruvate, the final metabolite of glycolysis, has a remarkable protective effect against different types of brain injury. The purpose of this study was to assess the neuroprotective effect and the neurological outcome after pyruvate administration in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in rats. Three doses of pyruvate (250, 500 and 1000 mg/kg, i.p.) or vehicle were administered intraperitoneally 30 min after pMCAO. In other set of experiments, pyruvate was given either before, immediately after ischemia or in a long-term administration paradigm. Functional outcome, mortality and infarct volume were determined 24 h after stroke. Even when the lowest doses of pyruvate reduced mortality and neurological deficits, no concomitant reduction in infarct volume was observed. The highest dose of pyruvate increased cortical infarction by 27% when administered 30 min after pMCAO. In addition, when pyruvate was given before pMCAO, a significant increase in neurological deficits was noticed. Surprisingly, on the contrary of what was found in the case of transient global ischemia, present findings do not support a great neuroprotective role for pyruvate in permanent focal cerebral ischemia, suggesting two distinct mechanisms involved in the effects of this glycolytic metabolite in the ischemic brain.