Protective effects of moderate hypothermia onneuronal death.

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In the first report of the present research project, we described that a slight lowering of the cerebral temperature caused a striking neuroprotection against ischemic damage. Since materials employed are of in vivo system or in vitro slices, rather functionally integrated ones, we attempted in this fiscal year (1) to use more simplified system, primary culture. Then we analyzed (2) the mode of action of MK-801, a chemical which has a nature to lower cerebral temperature and examined (3) the effect of the slight temperature lowering on blood viscosity, a problem which may be raised in clinical application of this procedure. Results obtained are as follow.(1)The primary culture experiments. When rat spinal neurons in culture were exposed to 200muM glutamate for 15min, and activity of liberated lactic dehydrogenase was analyzed to measure neuronal damage, there was practically no difference, between at 33ﾟC and 37ﾟC, in the extent of the death. It is deducible that effect of the lowering … More temperature can be observed in more integrated system in the term of their functions.(2)Mode of action of MK-801. MK-801, a non-selective antagonist of NMDA-type glutamate receptor subtype, apparently shows a marked neuroprotection by its temperature lowering action. In order to clarify this process, we attempted to follow cerebral temperature using a remote monitoring system that we developed newly. We found from these experiments that MK-801 does lose the set point of the cerebral temperature to allow the experimental animal to follow room temperature, a condition very mimic to poikilothermia.(3)Effect of temperature on blood viscosity of the dog. Under deep anesthesia and with a carotid-bypass, hypothermic dog was prepared. Blood samples from jugular vein were subjected to viscosity measurement using a cone-plate viscosimeter. At 21 sec shear rate, blood with Hematocrit 40 showed several % increase in the CP value (viscosity) by lowering blood temperature by 4ﾟC, a finding which is very akin to human blood. Less