Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse hippocampus.
Recent studies have shown that ethyl pyruvate (EP) acts as an anti-inflammatory molecule in several cell lines including RAW264.7 macrophages. However, the potential therapeutic value of EP for the treatment of the pathologic brain has not been investigated fully. In the present study, we examined whether EP has a beneficial effect on KA-induced neuronal cell death. Intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 mug) of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of EP significantly attenuated KA-induced neuronal cell death in these regions. Ethyl pyruvate was found to exert a protective effect when it was injected as late as 12 hr after KA-injection. Moreover, this EP-induced neuroprotection was accompanied by reduced levels of reactive gliosis and COX-2, IL-1beta, and TNF-alpha in the hippocampus. In addition, in passive avoidance tests, KA-induced memory impairment was improved markedly by EP. These results suggest that EP has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.
Cho
Ik-Hyun
IH
Ewha Institute of Neuroscience and Department of Neuroscience, Ewha Womans University, Seoul, Republic of Korea.
Kim
Seung-Woo
SW
Kim
Jung-Bin
JB
Kim
Tae-Kyung
TK
Lee
Kang-Woo
KW
Han
Pyung-Lim
PL
Lee
Ja-Kyeong
JK
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011773:Pyruvates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011930:Reaction Time / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D011773:Pyruvates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D051546:Cyclooxygenase 2; D007608:Kainic Acid