Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate post-insult hypothermia.

In piglets studied on the first day of life transient hypoxia-ischaemia caused an increase in the fractions of necrotic and apoptotic cells in the cingulate sulcus compared to sham-operated controls. In animals subjected to the same hypoxic-ischaemic insult but cooled to 34.9 degrees C (mean tympanic membrane temperature) for 12 hours commencing after resuscitation the fraction of cells undergoing necrosis was unchanged and comparable to that in animals which were not cooled. However, the fraction of apoptotic cells was reduced and was similar to that in sham-operated controls. Thus hypothermia specifically inhibited apoptosis. This result has implications for understanding the mechanisms of delayed cerebral injury and for the use of hypothermia as a neural rescue strategy in the developing brain.