Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus.
Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of brain injury. Proposed mechanisms of neuroprotection include activation of gene pathways that decrease oxidative injury, inflammation, and apoptosis, while increasing vasculogenesis and neurogenesis. To determine the effects of rEpo on gene expression in 10-d-old BALB-c mice with unilateral brain injury, we compared microarrays from the hippocampi of brain-injured pups treated with saline or rEpo to similarly treated sham animals. Total RNA was extracted 24 h after brain injury and analyzed using Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. We identified sex-specific differences in hippocampal gene expression after brain injury and after high-dose rEpo treatment using single-gene and gene set analysis. Although high-dose rEpo had minimal effects on hippocampal gene expression in shams, at 24-h post brain injury, high-dose rEpo treatment significantly decreased the proinflammatory and antiapoptotic response noted in saline-treated brain-injured comparison animals.
Juul
Sandra E
SE
Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. sjuul@u.washington.edu
Beyer
Richard P
RP
Bammler
Theo K
TK
McPherson
Ronald J
RJ
Wilkerson
Jasmine
J
Farin
Federico M
FM
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007249:Inflammation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins; D012737:Sex Factors; D013997:Time Factors
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin