TY - JOUR
T1 - Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia-ischemia in rats
AU - Yata, Kenichiro
AU - Matchett, Gerald A.
AU - Tsubokawa, Tamiji
AU - Tang, Jiping
AU - Kanamaru, Kenji
AU - Zhang, John H.
N1 - Funding Information:
This study was supported by NIH grants NS45694, HD43120, NS43338, and NS53407 to JHZ.
PY - 2007/5/11
Y1 - 2007/5/11
N2 - 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.
AB - 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.
KW - Apoptosis
KW - G-CSF
KW - Neonatal hypoxia-ischemia
KW - Neuron
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U2 - 10.1016/j.brainres.2007.01.144
DO - 10.1016/j.brainres.2007.01.144
M3 - Article
C2 - 17359943
AN - SCOPUS:33947624681
SN - 0006-8993
VL - 1145
SP - 227
EP - 238
JO - Brain Research
JF - Brain Research
IS - 1
ER -