This Article Full Text Full Text (PDF) All Versions of this Article: 36/8/1672    most recent 01.STR.0000173406.04891.8cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, Y. Articles by Zhang, J. H. Search for Related Content PubMed PubMed Citation Articles by Sun, Y. Articles by Zhang, J. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB OXYGEN

(Stroke. 2005;36:1672.)
© 2005 American Heart Association, Inc.

Original Contributions

Neonatal Hypoxia/Ischemia Is Associated With Decreased Inflammatory Mediators After Erythropoietin Administration

From the Department of Neurosurgery (Y.S., J.H.Z.), Louisiana State University Health Sciences Center, Shreveport, La, and the Department of Physiology (J.W.V., J.H.Z.) and Division of Neurosurgery (J.H.Z.), Loma Linda University School of Medicine, Loma Linda, Calif.

Correspondence to John H. Zhang MD, PhD, Division of Neurosurgery, Loma Linda University Medical Center, 11234 Anderson St, Room 2562B, Loma Linda, CA 92354. E-mail johnzhang3910{at}yahoo.com

Background and Purpose— Erythropoietin (EPO), a hematopoietic growth factor, has been shown to be neuroprotective when administered as either a pretreatment or posttreatment. This study tested the hypothesis that one of the mechanisms of protection afforded by posttreatment with recombinant human EPO (rh-EPO) is an anti-inflammatory effect via inhibition of interleukin (IL)-1ß.

Methods— Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 90 minutes of hypoxia (8% O₂ at 37°C). Pups were divided into the following groups: control, hypoxia/ischemia, and hypoxia/ischemia plus rh-EPO. In the rh-EPO–treated pups, rh-EPO (5 U/g body weight IP) was administered starting 24 hours after the insult and then for 2 additional days. Samples were collected at 3, 7, 14, and 21 days after the insult. IL-1ß mRNA and protein levels were determined by quantitative real-time reverse transcription–polymerase chain reaction and ELISA. Tumor necrosis factor (TNF)- mRNA levels were determined by colorimetric microplate assay.

Results— rhEPO attenuated brain injury, as assessed by brain weight, and attenuated both the hypoxia/ischemia–induced increases in IL-1ß mRNA and protein levels. TNF- mRNA levels did not increase at 3 to 14 days after the hypoxic/ischemic insult.

Conclusions— Administration of exogenous rh-EPO starting 24 hours after a hypoxic/ischemic insult is neuroprotective in the neonatal rat. This neuroprotective activity prevented the secondary, delayed rise in IL-1ß and attenuated the infiltration of leukocytes into the ipsilateral hemisphere.

Key Words: cytokines • growth factors • hypoxia • inflammation • ischemia

This article has been cited by other articles:

				H. J. Kadhim, J. Duchateau, and G. Sebire Cytokines and Brain Injury: Invited Review J Intensive Care Med, July 1, 2008; 23(4): 236 - 249. [Abstract] [PDF]

				P. Trzonkowski, A. Debska-Slizien, A. Mysliwski, and B. Rutkowski Treatment with recombinant human erythropoietin is associated with rejuvenation of CD8+ T cell compartment in chronic renal failure patients Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3221 - 3227. [Abstract] [Full Text] [PDF]

				L. Cherian, J. C. Goodman, and C. Robertson Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 789 - 794. [Abstract] [Full Text] [PDF]

				C. L. Keogh, S. P. Yu, and L. Wei The Effect of Recombinant Human Erythropoietin on Neurovasculature Repair after Focal Ischemic Stroke in Neonatal Rats J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 521 - 528. [Abstract] [Full Text] [PDF]

				C. Hernandez, A. Fonollosa, M. Garcia-Ramirez, M. Higuera, R. Catalan, A. Miralles, J. Garcia-Arumi, and R. Simo Erythropoietin Is Expressed in the Human Retina and It Is Highly Elevated in the Vitreous Fluid of Patients With Diabetic Macular Edema. Diabetes Care, September 1, 2006; 29(9): 2028 - 2033. [Abstract] [Full Text] [PDF]

				I. Solaroglu, J. Cahill, V. Jadhav, and J. H. Zhang Response to Letter by Schabitz et al Stroke, July 1, 2006; 37(7): 1655 - 1655. [Full Text] [PDF]