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Granulocyte‐Colony Stimulating Factor Exerts Neuroprotection in the Neonatal Hypoxia‐Ischemia Rat Model via the Hypothalamic‐Pituitary‐Adrenal Axis
Author(s) -
Charles Melissa,
Ostrowski Robert,
Manaenko Anatol,
Duris Kamil,
Zhang John,
Tang Jiping
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb690
Subject(s) - neuroprotection , medicine , endocrinology , dexamethasone , glucocorticoid , corticosterone , adrenocorticotropic hormone , granulocyte colony stimulating factor , hypoxia (environmental) , hematopoietic growth factor , metyrapone , ischemia , hormone , biology , chemistry , haematopoiesis , chemotherapy , organic chemistry , oxygen , stem cell , genetics
Neonatal hypoxia ischemia (HI) remains the leading cause of perinatal brain injury affecting 60% of preterm infants. Several reports suggest that the activity of the hypothalamic‐pituitary‐adrenal (HPA) axis is increased after HI. Granulocyte‐colony‐stimulating factor (G‐CSF) is a neuroprotective drug shown to modulate the HPA axis in the adult rat by regulating the adrenocorticotropic hormone (ACTH) and corticosterone (CORT). We hypothesize that G‐CSF confers neuroprotection in neonatal HI by suppressing the activity of the HPA axis. To test the hypothesis Metyrapone (MET), a CORT synthesis inhibitor, and dexamethasone (DEX,) a synthetic glucocorticoid, was administered separately or in combination with G‐CSF. HI was induced in P7 rats following a modified Rice‐Vanucci model, which were randomly assigned to groups and treated one hour after HI. We report that G‐CSF is neuroprotective in neonatal HI by reducing infarct volume, and regulating CORT levels. The combination of G‐CSF and MET increased weight gain, and significantly decreased pro‐apoptotic markers in the brain; while DEX reversed the effects of G‐CSF.