Stys P K, Waxman S G, Ransom B R
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.
J Cereb Blood Flow Metab. 1992 Nov;12(6):977-86. doi: 10.1038/jcbfm.1992.135.
Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42 degrees C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to < 37 degrees C caused a reversible increase in the CAP area and in the latencies of all three CAP peaks; increasing the temperature to > 37 degrees C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by 2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering the temperature to 32 degrees C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 +/- 14% of the control CAP area). Conversely, if temperature was increased to > 37 degrees C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following anoxia at 37 degrees C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O2 consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It is more likely that temperature affects the rate of ion transport by the Na(+)-Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.
已知温度会影响脑灰质缺氧/缺血性损伤的程度。我们采用离体大鼠视神经这一典型的中枢神经系统白质束（Foster等人，1982年），检验了如下假设：缺氧暴露期间温度的微小变化可能会影响白质中所见的功能损伤程度。通过对复合动作电位（CAP）面积进行定量评估来监测缺氧后的功能恢复情况。在32至42摄氏度范围内，环境温度的微小变化在常氧条件下会轻微影响视神经的CAP。将温度降至<37摄氏度会导致CAP面积以及所有三个CAP峰的潜伏期出现可逆性增加；将温度升至>37摄氏度则会产生相反的效果。缺氧60分钟后白质的功能恢复受到缺氧期间温度的强烈影响。在37摄氏度进行60分钟缺氧后，相对于对照组，CAP的平均恢复率为35.4±7%；当在缺氧暴露期间温度降低2.5摄氏度（即降至34.5摄氏度）时，功能恢复程度提高到64.6±15%（p<0.00001）。在缺氧暴露60分钟期间将温度降至32摄氏度会导致更大程度的功能恢复（为对照组CAP面积的100.5±14%）。相反，如果在缺氧期间温度升至>37摄氏度，功能结果会变差，例如在42摄氏度时CAP恢复率为8.5±7%（p<0.00001）。在37摄氏度缺氧后立即进行30分钟的低温（即32摄氏度）处理并不能改善功能结果。脑内的许多过程对温度敏感，包括氧气消耗，目前尚不清楚其中哪一个过程与观察到的温度对缺氧性损伤后白质恢复的影响最为相关。与灰质中的情况不同，缺氧性损伤的温度依赖性与谷氨酸等兴奋性毒素释放减少无关，因为神经递质在白质缺氧性损伤的病理生理学中不起作用（Ransom等人，1990a）。更有可能的是，温度会影响Na(+)-Ca2+交换体的离子转运速率，该转运体负责白质缺氧期间细胞内Ca2+的加载，和/或由细胞内Ca2+病理性增加激活的某些破坏性细胞内酶机制的速率。
