• Ylva Carlsson, Xiaoyang Wang, Leslie Schwendimann, Catherine I Rousset, Etienne Jacotot, Pierre Gressens, Marianne Thoresen, Carina Mallard, and Henrik Hagberg.
• Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. ylva.carlsson@vgregion.se
• Pediatr. Res. 2012 May 1;71(5):566-72.

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.MethodsThe 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.ResultsHI 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.DiscussionIn conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.

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