Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia-ischemia in rats

Kenichiro Yata, Gerald A. Matchett, Tamiji Tsubokawa, Jiping Tang, Kenji Kanamaru, John H. Zhang

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Neonatal hypoxia-ischemia (HI) is an important clinical problem with few effective treatments. Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has been shown to be neuroprotective in focal ischemia in vivo and is currently in phase I/II clinical trials for ischemic stroke in humans. We tested G-CSF in a rat model of neonatal hypoxia-ischemia in postnatal day 7 unsexed rat pups. Three groups of animals were used: hypoxia-ischemia (HI, n = 67), hypoxia-ischemia with G-CSF treatment (HI + G, n = 65), and healthy control (C, n = 53). G-CSF (50 μg/kg, subcutaneous) was administered 1 h after HI and given on four subsequent days (five total injections). Animals were euthanized 24 h, 1, 2, and 3 weeks after HI. Assessment included brain weight, histology, immunohistochemistry, and Western blotting. G-CSF treatment was associated with improved quantitative brain weight and qualitative Nissl histology after hypoxia-ischemia. TUNEL demonstrated reduced apoptosis in group HI + G. Western blot demonstrated decreased expression of Bax and cleaved caspase-3 in group HI + G. G-CSF treatment was also associated with increased expression of STAT3, Bcl-2, and Pim-1, all of which may have participated in the anti-apoptotic effect of the drug. We conclude that G-CSF ameliorates hypoxic-ischemic brain injury and that this may occur in part by an inhibition of apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)227-238
Number of pages12
JournalBrain Research
Volume1145
Issue number1
DOIs
StatePublished - May 11 2007

Keywords

  • Apoptosis
  • G-CSF
  • Neonatal hypoxia-ischemia
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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