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

Research output: Contribution to journalArticle

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

Fingerprint

Erythropoietin
Intravenous Injections
Rats
Plasmids
Ischemia
DNA
Gene therapy
Genetic Therapy
Brain Hypoxia-Ischemia
Child Mortality
Injections
Corpus Callosum
Wounds and Injuries
Infant Mortality
Cytomegalovirus
Intravenous Infusions
Neuroglia
Neuroprotection
Hypoxia
Tail

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats. / Wang, Cheng Haung; Liang, Chung Ling; Huang, Li Tung; Liu, Jong Kang; Hung, Pei Hua; Sun, Angel; Hung, Kuo Sheng.

In: Biochemical and Biophysical Research Communications, Vol. 314, No. 4, 20.02.2004, p. 1064-1071.

Research output: Contribution to journalArticle

Wang, Cheng Haung ; Liang, Chung Ling ; Huang, Li Tung ; Liu, Jong Kang ; Hung, Pei Hua ; Sun, Angel ; Hung, Kuo Sheng. / Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 314, No. 4. pp. 1064-1071.
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