Document Detail

Endotoxin increases sleep and brain allopregnanolone concentrations in newborn lambs.
MedLine Citation:
PMID:  12438667     Owner:  NLM     Status:  MEDLINE    
Infection has been identified as a risk factor for sudden infant death syndrome (SIDS). Synthesis of allopregnanolone, a neuroactive steroid with potent sedative properties, is increased in response to stress. In this study, we investigated the effect of endotoxin (lipopolysaccharide, LPS) on brain and plasma allopregnanolone concentrations and behavior in newborn lambs. LPS was given intravenously (0.7 micro g/kg) at 12 and 15 d of age (n = 7), and resulted in a biphasic febrile response (p < 0.001), hypoglycemia, lactic acidemia (p < 0.05), a reduction in the incidence of wakefulness, and increased nonrapid eye movement sleep and drowsiness (p < 0.05) compared with saline-treated lambs (n = 5). Plasma allopregnanolone and cortisol were significantly (p < 0.05) increased after LPS treatment. These responses to LPS lasted 6-8 h, and were similar at 12 and 15 d of age. Each lamb was then given LPS at 20 d of age and killed 3 h posttreatment to obtain samples of the brain. Allopregnanolone concentrations were increased (p < 0.05) in all brain areas except the cerebellum and diencephalon. We suggest that LPS-induced increase of allopregnanolone in the brain may contribute to somnolence in the newborn, and may be responsible for the reduced arousal thought to contribute to the risk of SIDS in human infants.
Saraid S Billiards; David W Walker; Benedict J Canny; Jonathan J Hirst
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  52     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-19     Completed Date:  2003-06-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  892-9     Citation Subset:  IM    
Department of Physiology, Monash University, Clayton, Victoria, Australia.
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MeSH Terms
Animals, Newborn
Bacterial Infections / complications
Brain / drug effects*,  metabolism*
Disease Models, Animal
Hydrocortisone / blood
Lipopolysaccharides / toxicity*
Pregnanolone / blood,  metabolism*
Pregnenolone / blood,  metabolism
Progesterone / blood,  metabolism
Risk Factors
Sleep / drug effects*
Sudden Infant Death / etiology
Reg. No./Substance:
0/Lipopolysaccharides; 128-20-1/Pregnanolone; 145-13-1/Pregnenolone; 50-23-7/Hydrocortisone; 57-83-0/Progesterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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