Neuroprotective Effect of Mild Hypothermia in Experimental Brain Ischemia

Summary

Modern hypothermia therapy has a history of more than a half century. However, this therapy was not commonly accepted as a treatment for cerebral damage because of its harmful complications and the lack of basic knowledge of its beneficial effects. In 1987, it was shown in animal experiments that lowering brain temperature only by a few degrees Celsius during ischemia could protect central neurons against ischemic damages. Since then, widespread basic experiments have started, providing useful information for the clinical application of hypothermia. The extent of neuronal protection by postischemic hypothermia depends on the time of introduction, the duration and the depth of hypothermia, and the degree of ischemic damages. In our gerbil models, hippocampal CA1 neurons were definitely protected against damage by hypothermia, initiated several hours after 5-min forebrain ischemia and maintained for 24h. In a focal ischemia model of the rat, hypothermia at 33°C for 24 h, which was introduced several hours after ischemia, decreased the infarct volume of the ischemic hemisphere. The mechanism underlying the protective effect of postischemic hypothermia is not clear yet. A growing body of evidence has indicated that lowering temperature depresses ischemia-induced glutamate release, intracellular calcium mobilization, and microglial activation along with the production of NO and superoxides. This lowering of temperature also restores postischemic protein synthesis, permeability of vessels, and the function of the blood-brain barrier, and obviously induces transcription factors like AP1, which may be linked to the synthesis of cytokines. Thus, the mode of action of hypothermia is broad and nonspecific and may be greatly advantageous in regard to cerebral protection against ischemic damage.