Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats

Cheng Haung Wang, Chung Ling Liang, Li Tung Huang, Jong Kang Liu, Pei Hua Hung, Angel Sun, Kuo Sheng Hung

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30 Citations (Scopus)

Abstract

Hypoxic-ischemic (H-I) encephalopathy is a major contributor to morbidity and mortality in infants and children. To delineate the nature and mechanism(s) of neuroprotection via erythropoietin (EPO) gene therapy, we evaluated the effects of single intravenous injection of naked plasmid DNA encoding EPO in H-I infant rats. Single administration of naked plasmid containing EPO cDNA driven under cytomegalovirus promoter (pCMV-EPO) by rapid injection via the tail vein produced a remarkable level of human EPO protein in the circulation, peaking at one day and lasting for 14 days after injection. There were significant improvements of water maze task in H-I rats after EPO gene therapy. Our data showed that the mechanisms of EPO gene therapy were rescue of CA1 neurons from lethal H-I injury, prevention of neuronal apoptosis in CA1 region, and decrease of glial activation in corpus callosum. This could be the first report of successful treatment of H-I injury by a single intravenous infusion of EPO gene.

Original languageEnglish
Pages (from-to)1064-1071
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number4
DOIs
Publication statusPublished - Feb 20 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • Erythropoietin
  • Gene therapy
  • Glial activation
  • Hypoxic-ischemic injury
  • Water maze task

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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