Influence of moderate hypothermia on ischemic brain damage incurred under hyperglycemic conditions.

Preischemic hyperglycemia aggravates brain damage following transient ischemia, and adds some special features to the damage incurred, notably a high frequency of postischemic seizures, cellular edema, and affectation of additional brain structures, such as the substanta nigra pars reticulata (SNPR). We raised the question whether mild intra-ischemic hypothermia (32-33 degrees C), known to reduce selective neuronal vulnerability in normoglycemic subjects, also ameliorates the characteristic damage observed in hyperglycemic animals. To that end, two series of experiments were performed. In the first, normo- and hypothermic animals were subjected to 10 min of ischemia during hyperglycemic conditions (plasma glucose 20-25 mmol.l-1), and allowed either 15 h or 1 week of recovery. In the second, both normo- and hyperglycemic animals were subjected to 15 min of ischemia (at normal or reduced temperature) and surviving animals were studied after 1 week of recovery. All normothermic, hyperglycemic animals developed postischemic seizures and died within the first 24 h. Mild hypothermia afforded substantial protection. Thus, 6/7 hypothermic animals subjected to 10 min of ischemia survived 1 week of recovery and none developed post-ischemic seizures. Of the hypothermic animals subjected to 15 min of ischemia 6/11 survived for 1 week, only one of which developed seizures. Protection by hypothermia was also shown by the histopathological analysis. Experiments with 10 min of ischemia and 15 h of recovery showed the expected damage in normothermic, hyperglycemic subjects. Hypothermia markedly reduced damage in all vulnerable structures, including the cingulate cortex and SNPR. The protection was most pronounced in the caudoputamen, where no affected neurons were seen in the hypothermic subjects. The experiments with 15 min of ischemia confirmed previous findings that mild hypothermia protects normoglycemic animals against the insult. The results also showed that hypothermia prevented most of the exaggeration of damage caused by hyperglycemia. However, under hypothermic conditions hyperglycemia still augmented damage in the cingulate cortex, medial and lateral venteroposterior thalamic nuclei, and SNPR, structures specifically damaged under hyperglycemic, normothermic conditions. This suggests that hypothermia has less of a protective effect on mechanisms causing such damage than on neuronal damage in the classic selectively vulnerable regions, particularly the caudoputamen.