| Combined effect of hypothermia and Caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury. | |
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MedLine Citation:
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PMID: 22322383 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hypoxic-ischemic (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 saving one infant in nine 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. The aim of the present study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI in mice. HI brain injury was moderately reduced in caspase-2(-/-) mice compared with wild-type mice. 5 h of hypothermia induced (33ºC versus normothermia 36°C) directly after HI provided additive protection overall (temperature p=0.0004, Caspase-2 genotype p=0.0029), in 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 hippocampus, but not in other brain areas. In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection compared with hypothermia alone. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-2-09 |
Journal Detail:
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Title: Pediatric research Volume: - ISSN: 1530-0447 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Neuroscience and Physiology [Y.C., X.W., C.I.R., C.M., H.H.], Sahlgrenska Academy at University of Gothenburg, Gothenburg 40530, Sweden [2] Department of Obstetrics and Gynecology [Y.C., H.H.], Sahlgrenska University Hospital, Gothenburg 41685, Sweden. |
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