Erythropoietin is neuroprotective in a preterm ovine model of endotoxin-induced brain injury

Rees, Sandra, Hale, Nadia, De Matteo, Robert, Cardamone, Lisa, Tolcos, Mary, Loeliger, Michelle, Mackintosh, Anna, Shields, Amy, Probyn, Megan, Greenwood, Deanne and Harding, Richard (2010) Erythropoietin is neuroprotective in a preterm ovine model of endotoxin-induced brain injury. Journal of Neuropathology and Experimental Neurology, 69 3: 306-319. doi:10.1097/NEN.0b013e3181d27138

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Author Rees, Sandra
Hale, Nadia
De Matteo, Robert
Cardamone, Lisa
Tolcos, Mary
Loeliger, Michelle
Mackintosh, Anna
Shields, Amy
Probyn, Megan
Greenwood, Deanne
Harding, Richard
Title Erythropoietin is neuroprotective in a preterm ovine model of endotoxin-induced brain injury
Journal name Journal of Neuropathology and Experimental Neurology   Check publisher's open access policy
ISSN 0022-3069
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1097/NEN.0b013e3181d27138
Volume 69
Issue 3
Start page 306
End page 319
Total pages 14
Place of publication Philadelphia, PA, U.S.A.
Publisher Lippincott Wiliams & Wilkins
Collection year 2011
Language eng
Formatted abstract
Intrauterine infection and inflammation have been linked to preterm birth and brain damage. We hypothesized that recombinant human erythropoietin (rhEPO) would ameliorate brain damage in anovine model of fetal inflammation. At 107 ± 1 day of gestational age (DGA), chronically catheterized fetal sheep received on 3 consecutive days 1) an intravenous bolus dose of lipopolysaccharide ([LPS] ∼0.9 μg/kg; n = 8); 2) an intravenous bolus dose of LPS, followed at 1 hour by 5,000 IU/kg of rhEPO (LPS + rhEPO, n = 8); or 3) rhEPO (n = 5). Untreated fetuses (n = 8) served as controls. Fetal physiological parameters were monitored, and fetal brains and optic nerves were histologically examined at 116 ± 1 DGA. Exposure to LPS, but not to rhEPO alone or saline, resulted in fetal hypoxemia, hypotension (p < 0.05), brain damage, including white matter injury, and reductions in numbers of myelinating oligodendrocytes in the corticospinal tract and myelinated axons in the optic nerve (p < 0.05 for both). Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but reduced brain injury and was beneficial to myelination in the corticospinal tract and the optic nerve. This is the first study in a long-gestation species to demonstrate the neuroprotective potential of rhEPO in reducing fetal brain and optic nerve injury after LPS exposure.
Copyright © 2010 by the American Association of Neuropathologists, Inc.
Keyword Erythropoietin
Fetal brain injury
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
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Created: Tue, 22 Mar 2011, 08:37:24 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences