Neuroprotective Effects of Hypothermia

Abstract

The beneficial effect of hypothermia on the treatment of ischemic cerebral damages has been explored since last several decades. However, less attention has been paid then on the application of hypothermia because of hampered complications and lack of basic knowledges. In the 1980s at long last, it was shown in the animal experiments that lowering temperature only by a few degrees could rescue central neurons against ischemic damages; seemingly the dawn of the second generation of hypothermia. In the animal models of transient global ischemia or focal ischemia, mild to moderate intraischemic hypothermia provided aremarkably protective effect on neurons, both histologically and functionally. A therapeutically relevant issue might be whether such hypothermia, even when introduced in the postischemic period, could also be neuroprotective against ischemic cerebral damages. At least in gerbil models, hippocampal CA 1 neurons were definitely rescued by hypothermia for 24hrs following transient forebrain ischemia for 5min and then normothermic reperfusion for couples of hrs. On the other hand, hypothermia on permanent focal cerebral ischemia has been considerably less studied than global ischemia, results obtained being still shaky.The mechanism underlying the protective effect of postischemic hypothermia are not clear yet. However, a growing body of evidence has indicated that lowering temperature depresses ischemia induced glutamate release, intracellular calcium mobilizaion, and microglial activation along with production of NO and superoxides. It also restores postischemic protein synthesis, permeability of vessels, and the function of blood-brain barrier, and obviously induce transcription factors like AP 1 which may link to synthesis of cytokines. Thus, mode of action of hypothermia is broad and non-specific, which may be greatly of advantage in regard to cerebral protection against ischemic damages.