Transient benefits but lack of protection by sodium pyruvate after 2-hour middle cerebral artery occlusion in the rat.

Sodium pyruvate has shown protective effects in various experimental models of brain ischemia. The main holdup of this drug is that most of the benefits are reported with a very narrow time window for intervention. Here we investigated whether pyruvate could protect the brain against ischemic damage using a model of 2-hour middle cerebral artery occlusion in the rat. The time course of blood pyruvate after i.p. administration of sodium pyruvate (400 mg/kg) was studied. Animals were treated with the drug or with vehicle 45 min after reperfusion following 2-hour ischemia. Tissue ATP content was determined 5 and 10 h after ischemia onset, and infarct volume was measured at days 1 and 2. The neurological score was evaluated before and after treatment in the different experimental groups. Pyruvate prevented the drop of cortical ATP induced by ischemia in the ipsilateral cortex and ameliorated the neurological deficit at 5 h after the onset of ischemia, supporting some beneficial effects of the treatment. However, these effects were not sustained at 10 h. Furthermore, pyruvate failed to significantly reduce infarct volume and the neurological deficit at 24 and 48 h, in spite of some trend to smaller infarction after pyruvate administration. Therefore, under the present experimental conditions, systemic administration of sodium pyruvate at 3 h after the beginning of ischemia exerted only a transient benefit but not a persistent protection against brain damage.