Protective effects of moderate hypothermia onneuronal death.

中度低温对神经元死亡的保护作用。

• 批准号: 03557007
• 负责人: KATAOKA Kiyoshi
• 金额: $ 1.28万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03557007/
• 关键词: ischemic neuronal death; moderate hypothermia; culture; glutamate; calcium; MK-801; blood-viscosity; neuronal protection; スナネズミ; 海馬; 脳温; マイクロダイアリシス; 遅発性ニュ-ロン死; ニュ-ロン保護作用

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

在本研究项目的第一份报告中，我们描述了脑温度的轻微降低引起了对缺血性损伤的显着神经保护。由于采用的材料是体内系统或体外切片，而不是功能完整的材料，因此我们在本财政年度（1）尝试使用更简化的系统，即原代培养。然后，我们分析了（2）MK-801（一种具有降低大脑温度性质的化学物质）的作用方式，并检查了（3）轻微降温对血液粘度的影响，这是该程序临床应用中可能出现的问题。所得结果如下。（1）原代培养实验。将培养的大鼠脊髓神经元暴露于200 μ M谷氨酸15分钟，分析释放的乳酸脱氢酶的活性以测量神经元损伤，在33 ℃和37 ℃之间，死亡程度几乎没有差异。可以推断， ...更多信息 温度可以在更完整的系统中观察到。（2）MK-801的作用方式。MK-801是NMDA型谷氨酸受体亚型的非选择性拮抗剂，通过其降温作用显示出明显的神经保护作用。为了阐明这一过程，我们尝试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确实失去了大脑温度的设定点，使实验动物能够遵循室温，这是一种非常类似于变温症的条件。（3）温度对犬血液粘度的影响。在深度麻醉和颈动脉旁路术下，准备低温犬。使用锥板粘度计对来自颈静脉的血液样品进行粘度测量。在21秒的剪切速率下，通过将血液温度降低4 ° C，红细胞比容40的血液显示CP值（粘度）增加了几个百分点，这一发现非常类似于人血。少

项目成果

Y.Andou: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil." Acta Neuropathol.85. 10-14 (1992)

Y.Andou：“重新评估常温沙鼠海马区缺血引起的神经元损伤。”

Akira Mitani: "Transient forebrain ischemia of three-mi nute duration consistenly induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil." Neurosci.Lett.131. 171-174 (1991)

Akira Mitani：“三分钟持续时间的短暂前脑缺血始终会导致常温沙鼠海马 CA1 区的严重神经元损伤。”

K.KATAOKA: "Binding of [^3H]MK-801,NMDA-displaceable[^3H]glutamate,[^3H]glycine,[^3H]spermidine,[^3H]kainate and [^3H]AMPA to regionally discrete brain membranes of the gerbil." Neurochem.Internat.22. 37-43 (1993)

K.KATAOKA：“[^3H]MK-801、NMDA 可置换的[^3H]谷氨酸、[^3H]甘氨酸、[^3H]亚精胺、[^3H]红藻氨酸和 [^3H]AMPA 与区域离散的结合

A.Mitani: "Selective vulnerability of hippocampal GAl neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil." Neuroscience. 48. 307-313 (1992)

A.Mitani：“海马 GA1 神经元的选择性脆弱性不能用沙鼠缺血期间谷氨酸浓度的增加来解释。”

A.Mitani: "Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil." Neuroscience. 48. 307-313 (1992)

A.Mitani：“海马 CA1 神经元的选择性脆弱性不能用沙鼠缺血期间谷氨酸浓度的增加来解释。”