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

Abstract

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.

• Authors: Ylva Carlsson, Xiaoyang Wang, Leslie Schwendimann, Catherine I Rousset, Etienne Jacotot, Pierre Gressens, Marianne Thoresen, Carina Mallard, Henrik Hagberg
• Journal: Pediatric research (Pediatr Res) Vol. 71 Issue 5 Pg. 566-72 (May 2012) ISSN: 1530-0447 [Electronic] United States
• PMID: 22322383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caspase 2

Topics

• Animals
• Animals, Newborn
• Caspase 2 (genetics)
• Hypothermia, Induced
• Hypoxia-Ischemia, Brain (prevention & control)
• Mice
• Mice, Knockout