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 1 infant in 9 from developing neurological deficits. The aim of the present study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency in a mouse model of HI. HI brain injury was significantly lower in caspase-2-/- animals compared with heterozygotes and wild-type animals. Administration of 5 h of hypothermia directly after HI provided additional protection in mice with caspase-2 gene deletion (temperature p=0.0004, genotype p=0.0029). This was especially noticeable in hippocampus and thalamus. Hypothermia protected wild-type animals to the same degree as that provided by caspase-2 gene deletion alone. Even hypothermia delayed 2 h after HI offered protection in this neonatal mouse model of HI, decreasing both gray (p=0.0486) and white matter (p=0.02) injury. In conclusion, caspase-2 gene deficiency combined with hypothermia provided stronger neuroprotection than hypothermia alone.
|Translated title of the contribution||Combined effect of hypothermia and Caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury|
|Article number||e-pub Feb 2012|
|Number of pages||7|
|Early online date||9 Feb 2012|
|Publication status||Published - May 2012|