Abstract
Erythropoietin (Epo) is neuroprotective in many models of brain injury. We developed a model of hypoxia-ischemia (HI) in P10 mice that results in consistent, moderate, brain injury with minimal acute mortality. Our objectives were to determine whether Epo is neuroprotective by comparing the degree of injury in sham, Epo and placebo-treated animals, and to catalog the time course of HI-induced changes in gene expression. We hypothesized that early changes in gene expression will mediate Epo neuroprotection. The right carotid artery of anesthetized P10 BALB/c mice was cauterized under direct visualization (n=100 total). Animals were then exposed to alternating hypoxia (8% oxygen x 15 minutes) and hyperoxia (100% oxygen x 10 minutes) for a total of 45 minutes of hypoxia, 20 minutes of hyperoxia at 34 C. Shams underwent anesthesia and visualization of the carotid artery only. After injury, mice were treated with either daily rEpo (5000 U/kg) SQ x 3, or placebo. RNA was extracted from the right hippocampus, cortex and diencephalon 1, 2, or 7 days after injury. The Code-link platform was used to compare gene expression. Triplicate RNA samples from each condition were pooled for analysis. Results: 18 of 33 rEpo-treated animals were grossly normal (55%), as compared to 8 of 35 placebo-treated animals (23%), p<0.01. The brain injury scores of Epo-treated animals were lower than placebo controls (1.76 vs 2.83, p < 0.001), indicating less severe injury. There were differences in the magnitude, timing and nature of the injury response across brain regions at all time points. Changes in gene expression included apoptosis, angiogenesis, and inflammatory genes. We conclude Epo is neuroprotective in this mouse model, that Epo significantly alters gene expression when compared to placebo control, and that acute changes in gene expression in response to neonatal HI differ across brain regions. NIH - R21 HD042213–01
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Juul, S., McPherson, R., Beyer, R. et al. 186 Erythropoietin is Neuroprotective in 10 Day Old Mice Subjected to Hypoxia Ischemia (USA). Pediatr Res 58, 386 (2005). https://doi.org/10.1203/00006450-200508000-00215
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DOI: https://doi.org/10.1203/00006450-200508000-00215