Document Detail


Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioral outcome following neonatal hypoxia-ischemia in rats.
MedLine Citation:
PMID:  22041713     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low-birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the 'female protection' following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI.
Authors:
C A Hill; M L Alexander; L D McCullough; R H Fitch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-27
Journal Detail:
Title:  Developmental neuroscience     Volume:  33     ISSN:  1421-9859     ISO Abbreviation:  Dev. Neurosci.     Publication Date:  2011  
Date Detail:
Created Date:  2012-03-21     Completed Date:  2012-07-18     Revised Date:  2013-12-30    
Medline Journal Info:
Nlm Unique ID:  7809375     Medline TA:  Dev Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  494-504     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Behavior, Animal / physiology*
Benzoquinones / pharmacology
Female
Hypoxia-Ischemia, Brain / metabolism*
Male
Rats
Rats, Wistar
Sex Characteristics*
X-Linked Inhibitor of Apoptosis Protein / metabolism*
Grant Support
ID/Acronym/Agency:
HD049792/HD/NICHD NIH HHS; R01 HD049792/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Benzoquinones; 0/X-Linked Inhibitor of Apoptosis Protein; 550-24-3/embelin
Comments/Corrections

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