Abstract
Extremely premature infants often display signs of cognitive and motor dysfunction in later life. Previous studies have shown that neurological deficits may correlate with a loss of brain cells. Until now, hypoxia and inflammation and infection were viewed as the sources of tissue damage. In recent studies, oxygen therapy has been identified as a cause of widespread apoptotic neurodegeneration in the developing brain. These findings were associated with downregulation of neurotrophic factors. The present study investigated whether systemically administered erythropoietin, a hematopoietic growth factor with neuroprotective properties, may ameliorate brain damage induced by hyperoxia in infant rats. 6-day old Wistar rats were subjected to 80% oxygen for 24 hours and EPO was co-administered at several doses, 10.000 - 20.000 I.E. at the beginning of exposure. Pups receiving either no treatment, EPO-treatment, or hyperoxia in combination with vehicle treatment served as controls. Pups were sacrificed at 24 hours of exposure to oxygen, transcardially perfused and brains were subjected to De Olmos silver and Fluoro-Jade staining. Morphometric analysis of 10 different brain regions to determine the extent of damage revealed that hyperoxia-induced neurodegeneration was significantly attenuated in EPO treated animals. The maximum neuroprotective effect was achieved with a single dose of 20000 IE/kg, p<0.001, primarily in the cortex and the thalamus nucleii. These findings suggest EPO as a potential neuroprotective agent in hyperoxia-induced cell death in the immature brain.
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Genz, K., Dzietko, M., Moysich, A. et al. 141 Neuroprotective Effect of Erythropoietin in Oxygen-Induced Cell Death in the Immature Brain. Pediatr Res 58, 378 (2005). https://doi.org/10.1203/00006450-200508000-00170
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DOI: https://doi.org/10.1203/00006450-200508000-00170