Caffeic acid phenethyl ester prevents neonatal hypoxic-ischaemic brain injury

Xing Wei, Liming Zhao, Zhizhong Ma, David M. Holtzman, Chong Yan, Richard C. Dodel, Harald Hampel, Wolfgang Oertel, Martin R. Farlow, Yansheng Du

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Neonatal hypoxic-ischaemic (HI) brain injury resulting in encephalopathy is a leading cause of morbidity and mortality with no effective treatment. Here we show that caffeic acid phenethyl ester (CAPE), an active component of propolis, administered either before or after an HI insult, significantly prevents HI-induced neonatal rat brain damage in the cortex, hippocampus and thalamus. In addition to blocking HI-induced caspase 3 activation, CAPE also inhibits HI-mediated expression of inducible nitric oxide synthase and caspase 1 in vivo and potently blocks nitric oxide-induced neurotoxicity in vitro. Furthermore, CAPE directly inhibits Ca2+-induced cytochrome c release from isolated brain mitochondria. Thus, CAPE induces neuroprotection against HI-induced neuronal death, possibly by blocking HI-induced inflammation and/or directly inhibiting the HI-induced neuronal death pathway. CAPE may therefore be a novel effective therapy for preventing neonatal HI injury.

Original languageEnglish (US)
Pages (from-to)2629-2635
Number of pages7
JournalBrain
Volume127
Issue number12
DOIs
StatePublished - Dec 2004

Keywords

  • Brain injury
  • Caffeic acid phenethyl ester
  • Hypoxia-ischaemia
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

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