Origin of Ischemia‐Induced Glutamate Efflux in the CA1 Field of the Gerbil Hippocampus: An In Vivo Brain Microdialysis Study
Origin of Ischemia‐Induced Glutamate Efflux in the CA1 Field of the Gerbil Hippocampus: An In Vivo Brain Microdialysis Study
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DOI：
10.1046/j.1471-4159.1994.63062152.x
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发表时间：
1994-12
影响因子：
4.7
通讯作者：
A. Mitani;Y. Andou;S. Matsuda;T. Arai;M. Sakanaka;K. Kataoka
中科院分区：
文献类型：
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作者：
A. Mitani;Y. Andou;S. Matsuda;T. Arai;M. Sakanaka;K. Kataoka
摘要：在沙鼠体内进行脑微透析实验，以评估短暂性缺血下细胞外谷氨酸积累的来源。将微透析探针置于海马 CA1 区，在微透析实验前 10-14 天，5 分钟缺血已诱导星形胶质细胞增殖、CA1 锥体神经元死亡和突触前末梢损伤；大脑皮层白质中含有少量神经元、少量突触前末梢和大量星形胶质细胞；或在组织学正常的海马 CA1 区，然后诱导 5 或 20 分钟缺血。当诱导5分钟缺血时，在CA1区域中没有观察到谷氨酸含量显着增加，显示出星形胶质细胞增殖、CA1锥体神经元死亡以及突触前末梢和大脑皮层白质的损伤，而在组织学正常的CA1区域中观察到谷氨酸含量显着增加（15倍）。当诱导20分钟缺血时，在20分钟缺血开始后的前10分钟内，CA1区谷氨酸含量没有观察到明显增加，显示出星形胶质细胞增殖、CA1锥体神经元死亡以及突触前末梢和白质的损伤，但在20分钟缺血的最后10分钟期间，在这两个区域观察到缺血诱导的谷氨酸含量显着增加。在 20 分钟缺血期间，在海马的正常 CA1 区域观察到谷氨酸过度增加（100 倍）。当在微透析实验前 4-7 天将探针置于海马 CA1 区（其中已通过向侧脑室注射双侧红藻氨酸消除了 Schaffer 络脉和连合纤维的突触前末端，然后诱导 5 分钟缺血）时，在 5 分钟缺血的后半段观察到谷氨酸显着增加。这些结果表明，星形胶质细胞的谷氨酸流出不会导致5分钟缺血期间海马CA1区中缺血诱导的谷氨酸大量积累，但会导致缺血期间较长持续时间的缺血诱导的谷氨酸水平增加，并且5分钟缺血期间缺血诱导的CA1区谷氨酸流出主要来自神经元元件：突触前末梢和突触后神经元。
Abstract: In vivo brain microdialysis experiments were performed in the gerbil to evaluate the origin of accumulation of extracellular glutamate under transient ischemia. Microdialysis probes were positioned in the CA1 field of the hippocampus in which proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals had been induced by 5‐min ischemia 10–14 days before the microdialysis experiment; in the white matter of the cerebral cortex, which contained few neurons, few presynaptic terminals, and many astrocytes; or in the histologically normal CA1 field of the hippocampus, and then 5‐ or 20‐min ischemia was induced. When 5‐min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter of the cerebral cortex, whereas a significant increase in glutamate (15‐fold) was observed in the histologically normal CA1 field. When 20‐min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter during the first 10 min after the onset of 20‐min ischemia, but remarkable ischemia‐induced increases in glutamate were observed during the last 10 min of 20‐min ischemia in both areas. An excessive increase in glutamate (100‐fold) was observed during 20‐min ischemia in the normal CA1 field of the hippocampus. When a probe was positioned in the CA1 field of the hippocampus in which presynaptic terminals of Schaffer collaterals and commissural fibers had been eliminated by bilateral kainate injections into the lateral ventricles 4–7 days before the microdialysis experiment and then 5‐min ischemia was induced, a significant increase in glutamate was observed during the last half of 5‐min ischemia. These results suggest that the efflux of glutamate from astrocytes does not contribute to the large ischemia‐induced glutamate accumulation in the CA1 field of the hippocampus during 5‐min ischemia but contributes to the ischemia‐induced increase in glutamate level during ischemia with a longer duration and that ischemia‐induced efflux of glutamate in the CA1 field during 5‐min ischemia originates mainly from neuronal elements: presynaptic terminals and postsynaptic neurons.