Erythropoietin Treatment Exacerbates Moderate Injury after Hypoxia-Ischemia in Neonatal Superoxide Dismutase Transgenic Mice
| Autor: | R Ann Sheldon, Christine Windsor, Byong Sop Lee, Donna M. Ferriero, Olatz Arteaga Cabeza |
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| Rok vydání: | 2017 |
| Předmět: |
Mouse
Hippocampus Striatum medicine.disease_cause Inbred C57BL Transgenic Mice 0302 clinical medicine Superoxide Dismutase-1 Brain injury Receptor Superoxide-dismutase biology Brain Recombinant Proteins Stroke Neurology Hypoxia-Ischemia Brain Cognitive Sciences medicine.drug Genetically modified mouse medicine.medical_specialty Physical Injury - Accidents and Adverse Effects SOD1 Models of Developmental Brain Injury and Therapy Mice Transgenic Superoxide dismutase Paediatrics and Reproductive Medicine 03 medical and health sciences Developmental Neuroscience 030225 pediatrics Internal medicine Hypoxia-Ischemia medicine Animals Humans Erythropoietin Neurology & Neurosurgery business.industry Neurosciences Newborn Brain Disorders Mice Inbred C57BL Oxidative Stress Endocrinology Good Health and Well Being Animals Newborn biology.protein business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Developmental neuroscience, vol 39, iss 1-4 |
| Popis: | The neonatal brain is highly susceptible to oxidative stress as developing endogenous antioxidant mechanisms are overwhelmed. In the neonate, superoxide dismutase (SOD) overexpression worsens hypoxic-ischemic injury due to H2O2 accumulation in the brain. Erythropoietin (EPO) is upregulated in 2 phases after HI, early (4 h) and late (7 days), and exogenous EPO has been effective in reducing the injury, possibly through reducing oxidative stress. We hypothesized that exogenous EPO would limit injury from excess H2O2 seen in SOD1-overexpressing mice, and thus enhance recovery after HI. We first wanted to confirm our previous findings in postnatal day 7 (P7) SOD-tg (CD1) mice using a P9 model of the Vannucci procedure of HI with SOD-tg mice from a different background strain (C57Bl/6), and then determine the efficacy of EPO treatment in this strain and their wild-type (WT) littermates. Thus, mice overexpressing copper/zinc SOD1 were subjected to HI, modified for the P9 mouse, and recombinant EPO (5 U/g) or vehicle (saline) was administered intraperitoneally 3 times: at 0 h, 24 h, and 5 days. Injury was assessed 7 days after HI. In addition, protein expression for EPO and EPO receptor was assessed in the cortex and hippocampus 24 h after HI. With the moderate insult, the SOD-tg mice had greater injury than the WT overall, confirming our previous results, as did the hippocampus and striatum when analyzed separately, but not the cortex or thalamus. EPO treatment worsened injury in SOD-tg overall and in the WT and SOD-tg hippocampus and striatum. With the more severe insult, all groups had greater injury than with the moderate insult, but differences between SOD-tg and WT were no longer observed and EPO treatment had no effect. Increased protein expression of EPO was observed in the cortex of SOD-tg mice given recombinant human EPO compared to SOD-tg given vehicle. This study confirms our previous results showing greater injury with SOD overexpression in the neonatal brain after HI at P7 in a different strain. These results also suggest that EPO treatment cannot ameliorate the damage seen in situations where there is excess H2O2 accumulation, and it may exacerbate injury in settings of extreme oxidative stress. |
| Databáze: | OpenAIRE |
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