| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2785842 | International Journal of Developmental Neuroscience | 2015 | 8 Pages |
•Hypoxic PC in newborn rats.•Causes corticosteroid surge.•Augments HI induced corticosteroid surge.•Preserves glucocorticoid feedback regulation after HI.•Glucocorticoid receptor blocker, RU486 before hypoxic PC.•Inhibits PC induced neuroprotection against HI.
Limited research has evaluated the corticosteroids (CS) response in hypoxic preconditioning (PC) induced neuroprotection against subsequent hypoxic-ischemic (HI) brain injury in newborns. To measure, CS response to hypoxic PC, at postnatal day 6 (P6), rat pups were randomly divided into sham, NoPC (exposure to 21% O2) and PC (exposure to 8% O2 for 3 h) groups. In a separate experiment, at P6, rat pups were randomly divided into three groups (sham, NoPC + HI, PC + HI). Rat pups in NoPC + HI and PC + HI groups, respectively had normoxic or hypoxic exposure for 3 h at P6 and then had the right carotid artery permanently ligated followed by 140 min of hypoxia at P7 (HI). Plasma CS levels were measured at 0.5, 1, 3, 6 and 12 h after hypoxic PC and hypoxic PC followed by HI. To investigate whether CS response to hypoxic PC provides neuroprotection against HI, at P6, rat pups were randomly divided into five groups. Fifteen minutes prior to PC or normoxic exposure, rat pups in DMSO + PC + HI and DMSO + NoPC + HI groups received DMSO while in RU486 + PC + HI and RU486 + NoPC + HI groups received RU486 (glucocorticoid receptor blocker, 60 mg/kg) s.c., respectively. Afterwards, rat pups were exposed to normoxia (DMSO + NoPC + HI, RU486 + NoPC + HI) or hypoxia (DMSO + PC + HI, RU486 + PC + HI) for 3 h and then HI 24 h later (P7). Rat pups at the corresponding age without any exposure to PC or HI or RU486/DMSO were used as sham. We found that hypoxic PC caused CS surge as well as augmented CS surge and preserved the glucocorticoid feedback regulation after HI. Hypoxic PC reduced HI induced early and delayed brain damage. RU486 partially but significantly inhibited hypoxic PC induced neuroprotection.
