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

Brain Res. 2005 Oct 26;1060(1-2):188-92. doi: 10.1016/j.brainres.2005.08.029. Epub 2005 Oct 13.

Abstract

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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cells, Cultured
  • Glucose / deficiency
  • Hydrogen Peroxide / pharmacology
  • Hypoxia / drug therapy
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Inflammation / drug therapy
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Oxidants / pharmacology
  • Pyruvates / pharmacology*
  • Rats

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Oxidants
  • Pyruvates
  • ethyl pyruvate
  • Hydrogen Peroxide
  • Glucose