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Endotoxin-induced hypoxic-ischemic tolerance is mediated by up-regulation of corticosterone in neonatal rat

Författare och institution:
Tomoaki Ikeda (-); Li Yang (-); Tsuyomu Ikenoue (-); Carina Mallard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Henrik Hagberg (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa)
Publicerad i:
Pediatr Res, 59 ( 1 ) s. 56-60
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Previous studies suggest that the endotoxin lipopolysaccharide (LPS) may have dual effects on brain damage induced by hypoxia-ischemia (HI) in 7-d-old rats, depending on the exposure paradigm. Although a 4-h interval between LPS administration and HI results in sensitization to HI brain injury, tolerance is observed when LPS is administered 24 h before HI. Our hypothesis is that endogenous corticosteroids are important in acquiring tolerance to HI. Neonatal rats received a single injection of LPS (1.0 mg/kg) either 4 h or 24 h before HI, or two LPS injections (4 h and 24 h) before HI. Increased brain injury was seen in animals subjected to a single LPS injection made 4 h before HI. In contrast, both the single 24-h exposure and the double injections of LPS resulted in tolerance to HI brain damage. To study the effects of corticosteroids on HI tolerance, RU486, a glucocorticoid receptor blocker, was subcutaneously injected at the same time as LPS (1.0 mg/kg), 24 h before HI stress. RU486-LPS treatment counteracted the LPS-induced tolerance effect, and aggravated the HI-induced brain injury compared with the vehicle-LPS-treated group. RU486 did not aggravate the HI-induced brain injury produced 24 h later in saline-injected animals. LPS (1.0 mg/kg) injected into 6-d-old rats transiently up-regulated serum corticosterone levels (119.6, 57.9, 56.8, and 28.3 ng/mL at 6, 12, 24, and 48 h after the LPS injection, respectively). We conclude that endotoxin-induced up-regulation of endogenous corticosterone appears to be critical for acquiring endotoxin-induced HI tolerance.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Animals, Newborn, Corticosterone/antagonists & inhibitors/blood/*metabolism, Hormone Antagonists/pharmacology, Hypoxia-Ischemia, Brain/metabolism/*prevention & control, Lipopolysaccharides/*therapeutic use, Mifepristone/pharmacology, Rats, Rats, Wistar, Up-Regulation
Postens nummer:
Posten skapad:
2007-09-21 09:58
Posten ändrad:
2010-01-26 12:43

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