Document Detail

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury.
MedLine Citation:
PMID:  22322383     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: [corrected] Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage.
METHODS: The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice.
RESULTS: HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 °C ) vs. normothermia (36 °C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas.
DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
Ylva Carlsson; Xiaoyang Wang; Leslie Schwendimann; Catherine I Rousset; Etienne Jacotot; Pierre Gressens; Marianne Thoresen; Carina Mallard; Henrik Hagberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-09
Journal Detail:
Title:  Pediatric research     Volume:  71     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-18     Completed Date:  2012-08-06     Revised Date:  2014-10-29    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  566-72     Citation Subset:  IM    
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MeSH Terms
Animals, Newborn*
Caspase 2 / genetics*
Hypothermia, Induced*
Hypoxia-Ischemia, Brain / prevention & control*
Mice, Knockout
Reg. No./Substance:
EC 3.4.22.-/Caspase 2

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