ISCHEMIC DAMAGE IN HIPPOCAMPAL CA1 IS DEPENDENT ON GLUTAMATE RELEASE AND INTACT INNERVATION FROM CA3
ISCHEMIC DAMAGE IN HIPPOCAMPAL CA1 IS DEPENDENT ON GLUTAMATE RELEASE AND INTACT INNERVATION FROM CA3
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DOI：
10.1038/jcbfm.1989.90
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发表时间：
1989-10-01
影响因子：
6.3
通讯作者：
DIEMER, NH
中科院分区：
文献类型：
--
作者：
BENVENISTE, H;JORGENSEN, MB;DIEMER, NH
已知通过破坏CA 3区来去除CA 1的多巴胺能传入神经可保护CA 1锥体细胞免受10分钟的短暂性全脑缺血。为了进一步研究谷氨酸的发病意义，我们测量了完整和CA 3损伤的CA 1海马组织中谷氨酸的释放。在完整的CA 1海马组织中，谷氨酸在缺血期间增加了6倍;然而，在CA 3损伤的CA 1区域中，谷氨酸在缺血期间仅增加了1.4倍。为了评估缺血诱导的谷氨酸释放的神经毒性潜力，我们将与正常、CA 3损伤和缺血性CA 1组织缺血期间释放的谷氨酸相同浓度的谷氨酸注射到CA 1区域。我们发现，当在对照（非缺血）条件下给药时，这种特定浓度的谷氨酸盐足以破坏完整和CA 3损伤的CA 1组织中注射部位附近的CA 1金字塔。相反，在缺血期间在CA 3损伤的CA 1区域中注射相同的量破坏了CA 1区域中注射部位周围广泛分布的区域中的锥体细胞。结论：海马CA 1区锥体细胞的缺血损伤依赖于谷氨酸的释放和来自CA 3区的完整神经支配。
The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA1 hippocampal tissue. In intact CA1 hippocampal tissue, glutamate is increased sixfold during ischemia; in the CA3-lesioned CA1 region, however, glutamate only increased 1.4-fold during ischemia. To assess the neurotoxic potential of the ischemia-induced release of glutamate, we injected the same concentration of glutamate into the CA1 region as is released during ischemia in normal, CA3-lesioned, and ischemic CA1 tissue. We found that this particular concentration of glutamate was sufficient to destroy CA1 pyramids in the vicinity of the injection site in intact and CA3-lesioned CA1 tissue when administered during control (non-ischemic) conditions. In contrast, the same amount injected during ischemia in the CA3-lesioned CA1 region destroyed pyramidal cells in a widely distributed zone around the injection site in the CA1 region. It is concluded that the ischemia-induced damage of pyramidal cells in CA1 is dependent on glutamate release and intact innervation from CA3.