Hypothermia and stroke: the pathophysiological background.

Hypothermia to mitigate ischemic brain tissue damage has a history of about six decades. Both in clinical and experimental studies of hypothermia, two principal arbitrary patterns of core temperature lowering have been defined: mild (32-35 degrees C) and moderate hypothermia (30-33 degrees C). The neuroprotective effectiveness of postischemic hypothermia is typically viewed with skepticism because of conflicting experimental data. The questions to be resolved include the: (i) postischemic delay; (ii) depth; and (iii) duration of hypothermia. However, more recent experimental data have revealed that a protected reduction in brain temperature can provide sustained behavioral and histological neuroprotection, especially when thermoregulatory responses are suppressed by sedation or anesthesia. Conversely, brief or very mild hypothermia may only delay neuronal damage. Accordingly, protracted hypothermia of 32-34 degrees C may be beneficial following acute cerebral ischemia. But the pathophysiological mechanism of this protection remains yet unclear. Although reduction of metabolism could explain protection by deep hypothermia, it does not explain the robust protection connected with mild hypothermia. A thorough understanding of the experimental data of postischemic hypothermia would lead to a more selective and effective clinical therapy. For this reason, we here summarize recent experimental data on the application of hypothermia in cerebral ischemia, discuss problems to be solved in the experimental field, and try to draw parallels to therapeutic potentials and limitations.