Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats.
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.
Wang
Cheng-Haung
CH
Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, ROC, Kaohsiung, Taiwan.
Liang
Chung-Ling
CL
Huang
Li-Tung
LT
Liu
Jong-Kang
JK
Hung
Pei-Hua
PH
Sun
Angel
A
Hung
Kuo-Sheng
KS
D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley
D004921:Erythropoietin; D004247:DNA