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Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

Neurochemical Research volume 34, Article number: 775 (2009) Cite this article

Abstract

The neuroprotective effects of ethyl pyruvate (EP), a stable derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia-reperfusion stress were investigated by 31P-nuclear magnetic resonance (31P-NMR) spectroscopy. Recovery level of phosphocreatine after ischemia was significantly greater when superfused with artificial cerebrospinal fluid (ACSF) with 2 mM EP than when superfused with ACSF without EP. EP was neuroprotective against ischemia only when administered before the ischemic exposure. Intracellular pH during ischemia was less acidic when superfused ahead of time with EP. EP did not show neuroprotective effects in neuron-rich slices pretreated with 100 μM fluorocitrate, a selective glial poison. It was suggested that both the administration of EP before ischemic exposure and the presence of astrocytes are required for EP to exert neuroprotective effects. We suggest the potential involvement of multiple mechanisms of action, such as less acidic intracellular pH, glial production of lactate, and radical scavenging ability.

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Acknowledgments

This study was funded by Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology, Japan to T.K. (# 17591639). The authors express sincere thanks to Dr. Kira Bacal, MD, PhD, MPH for her editing the manuscript and giving invaluable comments.

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Affiliations

  1. Department of Physiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Osamu Tokumaru, Chihiro Kuroki, Noriko Yoshimura, Tetsuro Sakamoto, Kazue Ogata, Naoko Nisimaru & Isao Yokoi

  2. Department of Pathology, The Methodist Hospital, Houston, TX, USA

    Hidehiro Takei

  3. Medical Education Center, Oita University Faculty of Medicine, Yufu, Oita, Japan

    Takaaki Kitano

Authors
  1. Osamu Tokumaru
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  2. Chihiro Kuroki
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  3. Noriko Yoshimura
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  4. Tetsuro Sakamoto
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  5. Hidehiro Takei
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  6. Kazue Ogata
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  7. Takaaki Kitano
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  8. Naoko Nisimaru
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  9. Isao Yokoi
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Correspondence to Osamu Tokumaru.

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Special issue article in honor of Dr. Akitane Mori.

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Tokumaru, O., Kuroki, C., Yoshimura, N. et al. Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study. Neurochem Res 34, 775 (2009). https://doi.org/10.1007/s11064-008-9871-x

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  • DOI: https://doi.org/10.1007/s11064-008-9871-x

Keywords

  • Ethyl pyruvate
  • Phosphocreatine
  • ATP
  • Brain energy metabolism
  • 31P-NMR
  • Ischemia-reperfusion injury