Exp Neurobiol 2007; 16(1): 9-17

Published online July 1, 2007

© The Korean Society for Brain and Neural Sciences

Pyruvate Reduces the Necrotic but not Apoptotic Component of OGD/Reoxygenation Injury in Primary Murine Cortical Neuronal Cultures

Hokyou Lee1, Jong Youl Kim1,2, Jong Eun Lee1,2, Won Taek Lee1 and Kyung Ah Park1*

1Department of Anatomy and 2BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea

Correspondence to: *To whom correspondence should be addressed.
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Pure neuronal cell cultures from fetal mice (15-day gestation) were cultured in order to investigate the effects of pyruvate in hypoxia. Primary neurons were injured in proportion to the oxygen concentration and duration of hypoxia in the culture. When concentrated pyruvate was supplied in the oxygen-glucose deprived condition (OGD), cell injury was prevented. In contrast, pyruvate did not attenuate apoptosis when supplied during reoxygenation after OGD. Hoechst-PI nuclear staining and Annexin-PI FACS analysis data were consistent with these observations. Although lactate, after being converted to pyruvate, goes through the same metabolic pathway as pyruvate, it did not increase cellular ATP levels as much as pyruvate, and did not induce apoptosis. We also investigated the expression of LDH isotypes, which catalyze the final step of anaerobic metabolism, glycolysis, in OGD primary cultured neurons with and without pyruvate or lactate. The expression of LDH-1 and LDH-5 was distributed differentially under OGD and reperfusion. During oxygen-glucose deprivation, LDH-1 was predominant and LDH-5 was often not detected at all. However, LDH-5 was the dominant isotype during reoxygenation.

Keywords: pyruvate, neuroprotection, OGD, reperfusion injury, cortical neuron