Protection by pyruvate against transient forebrain ischemia in rats

Pyruvate has a remarkable protective effect against zinc neurotoxicity. Because zinc neurotoxicity is likely one of the key mechanisms of ischemic brain injury, the neuroprotective effect of pyruvate was tested in a rat model of transient forebrain ischemia. Control experiments in mouse cortical culture showed that pyruvate almost completely blocked zinc toxicity but did not attenuate calcium-overload neuronal death. Adult rats subjected to 12 min forebrain ischemia exhibited widespread zinc accumulation and neuronal death throughout hippocampus and cortex 72 hr after reperfusion. However, rats injected intraperitoneally with sodium pyruvate (500-1000 mg/kg) within 1 hr after 12 min forebrain ischemia showed almost no neuronal death. In addition, the mortality was markedly decreased in the pyruvate-protected groups (3.8%) compared with the NaCl-injected control group (58.1%). The neuroprotective effect persisted even at 30 d after the insult. The spectacular protection without noticeable side effects makes pyruvate a promising neuroprotectant in human ischemic stroke.