Mechanisms of Erythropoietin-induced Brain Protection in Neonatal Hypoxia-Ischemia Rat Model

Yun Sun, Changman Zhou, Paula Polk, Anil Nanda, John H. Zhang

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Erythropoietin, a hemotopoietic growth factor, has brain protective actions. This study investigated the mechanisms of Recombinant Human EPO (rhEPO)-induced brain protection in neonates. An established rat hypoxia-ischemia model was used by ligation of the right common carotid artery of 7-day-old pups, followed by 90 minute of hypoxia (8% 02 and 92% N2) at 37°C. Animals were divided into three groups: control, hypoxia-ischemia, and hypoxia-ischemia plus rhEPO treatment. In rhEPO treated pups, 300 units rhEPO was administered intraperitoneally 24 hours before hypoxia. rhEPO treatment (300 units) was administered daily for an additional 2 days. ELISA and immunohistochemistry examined the expression of EPO and EPOR. Brain weight, morphology, TUNEL assay, and DNA laddering evaluated brain protection. rhEPO abolished mortality (from 19% to 0%) during hypoxia insult, increased brain weight from 52% to 88%, reduced DNA fragmentation, and decreased TUNEL-positive cells. Real-time RT-PCR, Western blot,and immunohistochemistry revealed an enhanced expression of heat shock protein 27 (HSP27) in ischemic brain hemisphere. Double labeling of TUNEL with HSP27 showed most HSP27 positive cells were negative to TUNEL staining. rhEPO reduces brain injury, especially apoptotic cell death after neonatal hypoxia-ischemia, partially mediated by the activation of HSP27.

Original languageEnglish (US)
Pages (from-to)259-270
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number2
StatePublished - Feb 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


  • Apoptosis
  • Brain injury
  • Heat shock protein
  • RT-PCR


Dive into the research topics of 'Mechanisms of Erythropoietin-induced Brain Protection in Neonatal Hypoxia-Ischemia Rat Model'. Together they form a unique fingerprint.

Cite this