TY - JOUR
T1 - Neuroprotective effects of ethyl pyruvate on brain energy metabolism after ischemia-reperfusion injury
T2 - A 31P-nuclear magnetic resonance study
AU - Tokumaru, Osamu
AU - Kuroki, Chihiro
AU - Yoshimura, Noriko
AU - Sakamoto, Tetsuro
AU - Takei, Hidehiro
AU - Ogata, Kazue
AU - Kitano, Takaaki
AU - Nisimaru, Naoko
AU - Yokoi, Isao
N1 - Funding Information:
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.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - P-NMR
KW - ATP
KW - Brain energy metabolism
KW - Ethyl pyruvate
KW - Ischemia-reperfusion injury
KW - Phosphocreatine
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U2 - 10.1007/s11064-008-9871-x
DO - 10.1007/s11064-008-9871-x
M3 - Article
C2 - 18985448
AN - SCOPUS:62349126169
SN - 0364-3190
VL - 34
SP - 775
EP - 785
JO - Neurochemical Research
JF - Neurochemical Research
IS - 4
ER -