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Study on the pathogenesis of cortical delayd neuronal death after transient cerebral ischemia

短暂性脑缺血后皮质迟发性神经元死亡发病机制的研究

基本信息

批准号：
05454657
负责人：
KUROIWA Toshihiko
金额：
$ 4.35万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

Various mechanisms such as impaired protein synthesis and microcirculatory disturbance have been proposed to explain the mechanism of delayd neuronal death. We examined regional differences in the activity of a mitochondrial respiratory enzyme, succinate dehydrogenase, in normal and postischemic gerbils using the quantitative imaging method.Gerbils of either sex were subjected to 5 min.of bilateral common carotid artery occlusion or permanent occlusion of left common carotid artery, and sacrificed at various time intervals after the ischemia. Some gerbils were sacrificed after a sham procedure. Coronal sections of the forebrain at 1.5mm posterior to the bregma were prepared for quantitative imaging of succinic dehydrogenase (SDH) activity. Histological change was evaluated using the same section after immersion fixation in buffered formalin and staining with HE and KB.In the control gerbils, SD activity in the pyramidal cell layr of the CA 1 sector was lower than in any other area of the hippocampus. In gerbils after transient ischemia, SD activity remained lowest in the Pyramidal cell layr of the CA 1 sector during the examination period. Histologically, selective neuronal necrosis was observed in the Pyramidal layr of the CA 1 sector at 2d and thereafter. After permanent occlusion of the common carotid artery, SDH activity decreased initially at the head of caudate and middle layr of cortex. The area of reduced SDH activity gradually enlarged to the whole area supplied by the ipsilateral carotid artery. Ischemic change by histological examination corresponded to the area of reduced SDH activity. These results showed that poor reserves of respiratory enzyme is the primary factor determining its selective vulnerability.

人们提出了多种机制，如蛋白质合成受损和微循环障碍来解释延迟神经元死亡的机制。我们使用定量成像方法检测了正常沙鼠和死后沙鼠线粒体呼吸酶琥珀酸脱氢酶活性的区域差异。双侧颈总动脉或左侧颈总动脉永久性闭塞5分钟后，雌雄沙鼠分别在缺血后的不同时间间隔处死。一些沙鼠在假手术后被处死。在脑脊液后1.5mm处制备前脑冠状面，定量成像琥珀酸脱氢酶（SDH）活性。在缓冲福尔马林浸泡固定后，用HE和KB染色，用同一切片评估组织学变化。在对照沙鼠中，ca1区锥体细胞层的SD活性低于海马的任何其他区域。沙鼠短暂缺血后，ca1区锥体细胞层的SD活性在观察期间最低。组织学上，ca1区锥体层在2d及之后出现选择性神经元坏死。永久性闭塞颈总动脉后，尾状头部和皮层中层SDH活性最初下降。SDH活性降低的区域逐渐扩大至整个同侧颈动脉供血区。组织学检查的缺血改变与SDH活性降低的区域相对应。这些结果表明，呼吸酶储备不足是决定其选择性易感性的主要因素。