Effect of erythropoietin on oxygen-induced brain injury in the newborn rat.
The developing nervous system is sensitive to supraphysiological oxygen concentrations. Recent studies showed that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. A wide variety of experimental studies have shown that erythropoietin exerts a remarkable neuroprotection in both cell cultures and in animal models of nervous system disorders. In the present study, we investigated the effect of erythropoietin against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+saline-treated group and hyperoxia+erythropoietin-treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in a plexiglas chamber in which the oxygen concentration was monitored twice daily from birth until postnatal day 5. Hyperoxia exposure was 24h/day for 5 days. The hyperoxia+erythropoietin group received an intraperitoneal injection of recombinant human erythropoietin at a dose of 1000U/(kgday). At postnatal day 5, all animals were sacrificed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that erythropoietin significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus and parietal cortex in hyperoxia+erythropoietin-treated group. Regarding the safety profile of erythropoietin in premature and mature infants, this agent may be potentially beneficial in preventing hyperoxic brain injury.
Yiş
Uluç
U
Department of Pediatric Neurology, School of Medicine, Dokuz Eylül University, Inciralti, 35340 Izmir, Turkey. ulyis@yahoo.com
Kurul
Semra Hiz
SH
Kumral
Abdullah
A
Tuğyan
Kazim
K
Cilaker
Serap
S
Yilmaz
Osman
O
Genç
Sermin
S
Genç
Kürşat
K
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D053938:DNA Fragmentation; D018891:Dentate Gyrus / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology; D018496:Hyperoxia / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018696:Neuroprotective Agents; D010100:Oxygen / Q000633:toxicity*; D010296:Parietal Lobe / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D010100:Oxygen