Ethyl pyruvate ameliorates intracerebral hemorrhage-induced brain injury through anti-cell death and anti-inflammatory mechanisms

Neuroscience. 2013 Aug 15;245:99-108. doi: 10.1016/j.neuroscience.2013.04.032. Epub 2013 Apr 24.

Abstract

Ethyl pyruvate (EP) is a pyruvate derivative and known to be cytoprotective in various pathological conditions through anti-cell death and anti-inflammatory mechanisms. The present study investigated the neuroprotective effect of ethyl pyruvate using a mouse model of collagenase-induced intracerebral hemorrhage (ICH). Our results showed that EP treatment to mice reduced brain edema and improved neurological function after ICH. Delayed treatment with EP until 6h after ICH to mice was still neuroprotective. We further demonstrated that EP protected neurons from hemoglobin-induced cell death in vitro and neuronal cell degeneration in ICH mice. Moreover, EP exerted anti-inflammatory effects by inhibiting microglia activation, nuclear factor-κB (NF-κB) DNA binding activity and subsequent downstream pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) production. Taken together, these results suggest that EP exerts neuroprotective effect via anti-cell death and anti-inflammatory actions. EP is a potential novel treatment for ICH patients and deserves further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cells, Cultured
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Male
  • Mice
  • Pyruvates / pharmacology
  • Pyruvates / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyruvates
  • ethyl pyruvate