Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia.

Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham-33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33 degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33 degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient-specific hypothermia protocols by combining systemic and selective cooling.

Delayed hypothermia prevents decreases in N-acetylaspartate and reduced glutathione in the cerebral cortex of the neonatal pig following transient hypoxia-ischaemia.

The effects of normothermia and delayed hypothermia on the levels of N-acetylaspartate (NAA), reduced glutathione (GSH) and the activities of mitochondrial complex I, II-III, IV and citrate synthase were measured in brain homogenates obtained from anaesthetized neonatal pigs following transient in vivo hypoxia-ischaemia. In the normothermic animals there was a significant decrease in complex I activity and in the levels of GSH and NAA when compared to the controls. Delayed hypothermia preserved NAA and GSH at control levels and enhanced the rate of complex II-III activity. There was correlation (R = 0.79) between GSH and NAA levels when data from all three experimental groups were analyzed. Citrate synthase activity was not significantly different in the three groups, indicating maintenance of mitochondrial integrity. These data suggest that delayed hypothermia affords protection of integrated mitochondrial function in the neonatal brain following transient hypoxia-ischaemia.