  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.
