Depth of delayed cooling alters neuroprotection pattern after hypoxia‐ischemia

Abstract

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.

Long-Term Neuroprotective Effect of Postischemic Hypothermia in a Neonatal Rat Model of Severe Hypoxic Ischemic Encephalopathy: A Comparative Study on the Duration and Depth of Hypothermia

“…This is in accord with the results of a few animal studies that focused on the effect of different HT target temperatures, although the temperature range varied among the studies (10,18 -19,22). Interestingly, another piglet study demonstrated a different HT temperature threshold between brain regions; whereas HT at 35°C and 33°C achieved better neuroprotection in the deep gray matter and in the cortical gray matter, respectively, (9). Whether this differential neuroprotection afforded by different HT target temperatures also applies to the smaller brain of the neonatal rat is uncertain.…”

Hypothermic neuroprotection

“…Intriguingly, recent short-term recovery studies in the piglet do suggest that the optimal degree of cooling is greater in the cortex than in the basal ganglia. 154 Supporting this experimental observation, in a recent case series, head cooling but not whole body cooling seemed to be associated with a reduction in the incidence of severe cortical lesions, 143 as examined by MRI. If this is correct, we would predict that the long-term followup of the CoolCap study may show a greater effect on cognitive ability.…”

Hypothermia for the treatment of infants with hypoxic–ischemic encephalopathy

“…Cooling to 33 1C preserved more neurons in the cortex and hippocampus and cooling to 35 1C preserved more neurons in the deep nuclear gray matter. 38 Initial pilot studies in human newborns described reproducible approaches to both selective head and whole-body hypothermic therapy and confirmed the feasibility of such therapies. [39][40][41][42][43][44] Although these studies noted mild physiological changes in cardiovascular status and the potential for minor permutations in coagulation measurements, they showed that these changes were not clinically significant, that both methods of cooling were practical and that there were no major short-term consequences or complications to either method of cooling.…”