NEUROPROTECTIVE EFFECTS OF ETHYL PYRUVATE ON ENERGY METABOLISM OF RAT BRAIN AFTER ISCHEMIA: A 31P-NMR STUDY

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Introduction : Pyruvate is not only an intermediary metabolite of energy metabolism but also a neuro-protectant as a potent antioxidant and free radical scavenger. It was reported that administration of pyruvate improved cerebral metabolic and functional status during hemorrhagic shock and reduced neuronal death after cerebral ischemia.Neuroprotective effects of ethyl pyruvate (EP), a stable and lipophilic derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia were investigated by phosphorous nuclear magnetic resonance (^<31>P-NMR) spectroscopy.Methods : Brain slices prepared from a male Wistar rat (6 week-old) were incubated in standard artificial cerebrospinal fluid (ACSF) with 2mM EP or ACSF only (control) at 25℃. The brain slices were exposed to ischemia by halting the perfusion for 1 hr. Recovery of the levels of high-energy phosphates, phosphocreatine (PCr), after reperfusion were measured by ^<31>P-NMR.Results : Recovery of the level of PCr after ischemia was significantly greater when EP was present in ACSF than in its absence (78.2 ± 3.3% vs 60.8 ± 1.9%, respectively; p = 0.001). EP was less effective when it was administered only during the recovery period (71.9 ± 4.6%; p = 0.059). When the brain slices were treated with 1001μM fluorocitrate (FC), a selective glial poison, PCr level was decreased to 92.0 ± 3.3% of the untreated level. In neuron-rich brain slices pretreated with FC, difference in recovery of the PCr level after ischemia was not detected (69.8 ± 6.4% vs 70.0 ± 4.5%; p = 0.66).Conclusions : These results indicated that EP is neuroprotective against ischemia when administered before the ischemic exposure. Our results also showed that EP did not show significant neuroprotective effects in neuron-rich slices pretreated with FC. It was suggested that the administration of EP before ischemia and the presence of glial cells are required for EP to exert neuroprotective effects.