Deferoxamine decreases the excitatory amino acid levels and improves the histological outcome in the hippocampus of neonatal rats after hypoxia-ischemia

Georgios Papazisis, Chryssa Pourzitaki, Chrysanthi Sardeli, Aimilios Lallas, Ekaterini Amaniti, Dimitrios Kouvelas

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxic-ischemic encephalopathy is a severe complication of perinatal asphyxia and causes lifelong deficits in infants and children. Multiple mechanisms acting in serial or parallel fashion are likely to be involved in this procedure. The neuronal injury is strongly related to iron-catalysed oxygen radical production and subsequent peroxidative damage to lipids and protein. Excessive release of excitatory amino acids (EAA) glutamate and aspartate, with consequent overstimulation of glutamate receptors, is also thought to be an important mechanism in this brain injury. Deferoxamine (DFO), a chelator of non-protein-bound iron, has been shown to inhibit lipid peroxidation and hydroxyl radical production via the Fenton reaction and to decrease hypoxic-ischemic and reperfusion associated brain injury. However, the exact mechanism of neuroprotection of DFO and its possible effect on the neurotransmitters' release is currently being investigated. In the present study, a well-established model of perinatal asphyxia was used to investigate the effect of DFO on hypoxic-ischemic-induced damage to different hippocampal brain structures. DFO was administrated subcutaneously immediately after the asphyctic insult. Histological examination of the hippocampus was conducted and the tissue levels of glutamate and aspartate in the same area were determined. A remarkable reduction of hypoxia-ischemia-evoked neurons in the CA1 hippocampal region and a decrease in the asphyxia-induced hippocampal tissue levels of glutamate and aspartate was noted after DFO treatment. These findings suggest a complex action of DFO, which could be neuroprotective when administrated in the immature brain immediately after hypoxia-ischemia.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalPharmacological Research
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • Deferoxamine
  • Excitatory amino acids
  • Hypoxia-ischemia
  • Neonatal rats
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmacology

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