Journal
BRAIN RESEARCH
Volume 1145, Issue -, Pages 227-238Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2007.01.144
Keywords
neonatal hypoxia-ischemia; G-CSF; apoptosis; neuron
Categories
Funding
- NICHD NIH HHS [HD43120, R01 HD043120] Funding Source: Medline
- NINDS NIH HHS [R01 NS043338, NS53407, NS45694, R01 NS045694, NS43338, R01 NS054685, R01 NS053407] Funding Source: Medline
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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 mu g/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.
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