Protective effects of moderate hypothermia onneuronal death.

在本研究项目的第一份报告中，我们描述了略微降低大脑温度可以对缺血性损伤产生显著的神经保护。由于所使用的材料是体内系统或体外切片，而不是功能集成的材料，我们在本财年(1)尝试使用更简化的系统，即原代培养。分析了具有降脑降温作用的化学物质MK-801的作用机制，考察了轻微降温对血液粘度的影响，这是临床应用中可能出现的一个问题。主要研究结果如下：(1)原代培养实验。培养的大鼠脊髓神经元暴露于200ﾟ/L谷氨酸15min后，以乳酸脱氢酶活力测定神经元的损伤程度，33ﾟC和37℃时的死亡程度几乎没有差别。可以推断，降低…效果从功能上看，集成程度越高的系统，温度越高。(2)MK-801的作用方式。NMDA型谷氨酸受体亚型的非选择性拮抗剂MK-801具有明显的降温作用。为了弄清这一过程，我们试图使用我们新开发的远程监测系统来跟踪大脑温度。我们从这些实验中发现，MK-801确实失去了脑温度的设定值，使实验动物能够跟随室温，这种情况非常类似于变温。(3)温度对狗血液粘度的影响。在深度麻醉下，颈动脉搭桥术，将犬降温。颈静脉血样用锥板式粘度计进行粘度测量。在21秒的切变率下，红细胞压积为40的血液通过将血温降低4ﾟC而使Cp值(粘度)增加几个百分点，这一发现与人类血液非常相似。较少

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