Corticosteroid responses following hypoxic preconditioning provide neuroprotection against subsequent hypoxic-ischemic brain injury in the newborn rats.
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 3h) 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 3h 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 12h 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 3h and then HI 24h 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.
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Yangzheng
Y
Feng
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: abhatt@umc.edu.
Abhay J
AJ
Bhatt
D000305:Adrenal Cortex Hormones / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000473:pathology / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D006727:Hormone Antagonists; D015735:Mifepristone; D053148:Caspase 3
CNS injury; Glucocorticoids; Hypoxic tolerance; Neuroprotection; Newborn rat