Anti-inflammatory mechanism is involved in ethyl pyruvate-mediated efficacious neuroprotection in the postischemic brain

被引:89
作者
Kim, JB [1 ]
Yu, YM [1 ]
Kim, SW [1 ]
Lee, JK [1 ]
机构
[1] Inha Univ, Sch Med, Dept Anat, Inchon 400712, South Korea
关键词
ethyl pyruvate; pyruvate; neuroprotection; microglia; ischemia;
D O I
10.1016/j.brainres.2005.08.029
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Ethyl pyruvate (EP) is a pyruvate derivative, and has recently been reported to prevent lethality in mice with established lethal sepsis and systemic inflammation. In a previous study, we reported that EP has a neuroprotective effect in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO), in which it was found to be effective when injected as late as 12 h after MCAO/reperfusion. In the present study, we show that therapeutic window of pyruvate in this MCAO animal model is limited to 1 h (30 min before and 30 min after MCAO). Moreover, both pyruvate and EP have a neuroprotective effect during oxygen-glucose deprivation (OGD) or H2O2 challenge in primary cortical culture. In contrast, EP suppressed the LPS-induced activation of primary microglia in culture, but pyruvate did not. The suppression of microglia activation was evidenced by a reduction in nitric oxide release and by a proinflammatory factor induction in primary microglia culture, which were accompanied by the repression of nuclear factor-kappa B activation. These results suggest that EP has a strong protective effect and a wide therapeutic window, and that this protective effect of EP is related to its anti-inflammatory action. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:188 / 192
页数:5
相关论文
共 25 条
  • [1] Bhat NR, 1998, J NEUROSCI, V18, P1633
  • [2] Acquired interferonγ responsiveness during Caco-2 cell differentiation:: effects on iNOS gene expression
    Chavez, AM
    Morin, MJ
    Unno, N
    Fink, MP
    Hodin, RA
    [J]. GUT, 1999, 44 (05) : 659 - 665
  • [3] Pathobiology of ischaemic stroke: an integrated view
    Dirnagl, U
    Iadecola, C
    Moskowitz, MA
    [J]. TRENDS IN NEUROSCIENCES, 1999, 22 (09) : 391 - 397
  • [4] Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia
    Dobsak, P
    Courderot-Masuyer, C
    Zeller, M
    Vergely, C
    Laubriet, A
    Assem, M
    Eicher, JC
    Teyssier, JR
    Wolf, JE
    Rochette, L
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1999, 34 (05) : 651 - 659
  • [5] Reactive oxygen species and cell signaling - Respiratory burst in macrophage signaling
    Forman, HJ
    Torres, M
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2002, 166 (12) : S4 - S8
  • [6] INTERLEUKIN-1 OF THE CENTRAL-NERVOUS-SYSTEM IS PRODUCED BY AMEBOID MICROGLIA
    GIULIAN, D
    BAKER, TJ
    SHIH, LCN
    LACHMAN, LB
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 164 (02) : 594 - 604
  • [7] GIULIAN D, 1997, PRIMER CEREBROVASCUL, P117
  • [8] GOLDBERG MP, 1993, J NEUROSCI, V13, P3510
  • [9] Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats
    González-Falcón, A
    Candelario-Jalil, E
    García-Cabrera, M
    León, OS
    [J]. BRAIN RESEARCH, 2003, 990 (1-2) : 1 - 7
  • [10] Ethyl pyruvate inhibits nuclear factor-κB-dependent signaling by directly targeting p65
    Han, YS
    Englert, JA
    Yang, RK
    Delude, RL
    Fink, MP
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 312 (03) : 1097 - 1105