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Erythropoietin Attenuates Inflammatory Factors and Cell Death in Neonatal Rats with Intracerebral Hemorrhage

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Intracerebral Hemorrhage Research

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 111))

Abstract

Stroke affects infants at a rate of 26/100,000 live births each year. Of these strokes, approximately 6.7 are hemorrhagic strokes. Erythropoietin (EPO) is an anti-apoptotic and neuroprotective hormone. In adult rodents, EPO attenuates inflammatory factor expression and blood–brain barrier damage after intracerebral hemorrhage (ICH). However, the effect of EPO in neonatal ICH stroke remains unexplored. This investigation aimed to elucidate the underpinnings of inflammation after ICH in postnatal day 7 (P7) rats and the effect of human recombinant EPO (hrEPO) treatment on ICH-induced inflammation. The P7 rat pups were pretreated with hrEPO (5,000 U/kg i.p.) or saline vehicle 4 h prior to the induction of ICH by blood injection into the right cerebral cortex and basal ganglia. Supplemental half doses of hrEPO treatment or saline injections were subsequently given 16 h after ICH induction. Real-time PCR done 24 h after ICH showed reductions in interleukin1-β (IL1-β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) mRNA expression in the basal ganglia of the hrEPO-treated rats compared to saline-treated rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining indicated fewer dying cells in the hrEPO-treated brain. Our data suggest that hrEPO has an anti-inflammatory action in neonates after ICH. The suppression of inflammatory cascades likely contributes to hrEPO’s neuroprotective effect, which may be explored as a therapeutic treatment for ICH.

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Acknowledgments

This work was supported by NIH grants NS058710 and NS062097, NS045155 and NS045810, and the American Heart Association Established Investigator Award.

Conflict of interest statement We declare that we have no conflict of interest.

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Chau, M., Chen, D., Wei, L. (2011). Erythropoietin Attenuates Inflammatory Factors and Cell Death in Neonatal Rats with Intracerebral Hemorrhage. In: Zhang, J., Colohan, A. (eds) Intracerebral Hemorrhage Research. Acta Neurochirurgica Supplementum, vol 111. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0693-8_50

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