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Article Dans Une Revue Pediatric Research Année : 2012

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury

Ylva Carlsson
  • Fonction : Auteur
Xiaoyang Wang
  • Fonction : Auteur
Leslie Schwendimann
  • Fonction : Auteur
Catherine I. Rousset
  • Fonction : Auteur
Pierre Gressens
Marianne Thoresen
  • Fonction : Auteur
Carina Mallard
  • Fonction : Auteur
Henrik Hagberg
  • Fonction : Auteur

Résumé

INTODUCTION: 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-imice as compared with wild-type (WT) mice. Five hours of hypothermia (33 degrees C) vs. normothermia (36 degrees 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.

Dates et versions

hal-01544172 , version 1 (21-06-2017)

Identifiants

Citer

Ylva Carlsson, Xiaoyang Wang, Leslie Schwendimann, Catherine I. Rousset, Etienne Jacotot, et al.. Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury. Pediatric Research, 2012, 71 (5), pp.566-572. ⟨10.1038/pr.2012.15⟩. ⟨hal-01544172⟩
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