Multiple pathways of neuroprotection against oxidative stress and excitotoxic injury in immature primary hippocampal neurons

Lynn M. Almli, Shannon E.G. Hamrick, Anita A. Koshy, Martin G. Täuber, Donna M. Ferriero

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

In the immature brain hydrogen peroxide accumulates after excitotoxic hypoxia-ischemia and is neurotoxic. Immature hippocampal neurons were exposed to N-methyl-D-aspartate (NMDA), a glutamate agonist, and hydrogen peroxide (H2O2) and the effects of free radical scavenging and transition metal chelation on neurotoxicity were studied. α-Phenyl-N-tert.-butylnitrone (PBN), a known superoxide scavenger, attenuated both H2O2 and NMDA mediated toxicity. Treatment with desferrioxamine (DFX), an iron chelator, at the time of exposure to H2O2 was ineffective, but pretreatment was protective. DFX also protected against NMDA toxicity. TPEN, a metal chelator with higher affinities for a broad spectrum of transition metal ions, also protected against H2O2 toxicity but was ineffective against NMDA induced toxicity. These data suggest that during exposure to free radical and glutamate agonists, the presence of iron and other free metal ions contribute to neuronal cell death. In the immature nervous system this neuronal injury can be attenuated by free radical scavengers and metal chelators.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalDevelopmental Brain Research
Volume132
Issue number2
DOIs
StatePublished - Dec 31 2001
Externally publishedYes

Keywords

  • Brain injury
  • Iron
  • Neonate
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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