Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats.
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.
Department of Pharmacology, University of Havana (CIEB-IFAL), Apartado Postal 6079, Havana City 10600, Cuba.
Armando
A
González-Falcón
Eduardo
E
Candelario-Jalil
Michel
M
García-Cabrera
Olga Sonia
OS
León
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology*; D002908:Chronic Disease; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D007274:Injections, Intraperitoneal; D008297:Male; D018696:Neuroprotective Agents; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D019289:Pyruvic Acid