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Vol. 94, No. 4, 2008
Issue release date: November 2008
Section title: Original Paper
Neonatology 2008;94:255–266
(DOI:10.1159/000151644)

Pretreatment with Low Doses of Erythropoietin Ameliorates Brain Damage in Periventricular Leukomalacia by Targeting Late Oligodendrocyte Progenitors: A Rat Model

Mizuno K. · Hida H. · Masuda T. · Nishino H. · Togari H.
Departments of aPediatrics and Neonatology and bNeurophysiology and Brain Science, Nagoya City University Graduate School of Medical Science, Nagoya, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/25/2007
Accepted: 10/4/2007
Published online: 9/11/2008

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 4

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO

Abstract

Background: One of the pathological hallmarks of periventricular leukomalacia (PVL) is the selective vulnerability of late oligodendrocyte progenitors (preoligodendrocytes; preOLs) to hypoxia-ischemia (H-I). It is unknown whether recombinant human erythropoietin (rhEPO) protects preOLs in vivo. Objectives: To develop a rat PVL model in which preOLs are selectively damaged and exhibit similar pathological changes to diffuse-type human PVL, various conditions of H-I were compared in P2–P7 rats (P2 = postnatal day 2). To evaluate the effect of rhEPO on oligoprotection (preOLs), rhEPO was administered to P3 PVL rats. Methods: After counts of NG2-positive and O4-positive cells were performed in P2–P7 rats, right common carotid artery occlusion followed by 6% O2 for 0–120 min was performed in P2–P4 rats. The mortality and histological alterations after hematoxylin/eosin staining and ED1 immunostaining were assessed 2 days after H-I. Various doses of rhEPO (1–30,000 U/kg i.p.) were administered to PVL rats 15 min before administration of 6% O2. Results: Double-positive cells for NG2 and O4 were detected from P2, and their number gradually increased until P7. Although right common carotid artery occlusion with 6% O2 for 60 min resulted in a relatively high proportion of deaths in P2–P4 rats, typical histological changes in the PVL diffuse component were found in most surviving P3 animals. With 50–100 U/kg rhEPO, the histological damage was attenuated. Conclusions: Histological changes similar to those seen in the PVL diffuse component were induced by H-I in P3 rats, in which preOLs were gradually developing, and a low dose of rhEPO was effective in the treatment of brain damage induced by H-I.


  

Author Contacts

Hideki Hida, MD, PhD
Department of Neurophysiology and Brain Science
Nagoya City University Graduate School of Medical Science
1 Kawasumi, Mizuho-ku, Nagoya 467-8601 (Japan)
Tel. +81 52 853 8135, Fax +81 52 842 3069, E-Mail hhida@med.nagoya-cu.ac.jp

  

Article Information

Received: April 25, 2007
Accepted after revision: October 4, 2007
Published online: September 11, 2008
Number of Print Pages : 12
Number of Figures : 5, Number of Tables : 4, Number of References : 54

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 94, No. 4, Year 2008 (Cover Date: November 2008)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661–7800 (Print), eISSN: 1661–7819 (Online)

For additional information: http://www.karger.com/NEO


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/25/2007
Accepted: 10/4/2007
Published online: 9/11/2008

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 4

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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