Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment
Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment
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DOI：
10.1097/00001756-199801050-00033
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发表时间：
1998-01
期刊：
影响因子：
1.7
通讯作者：
Steffany A. L. Bennett;M. Tenniswood;Jiahua Chen;C. M. Davidson;M. T. Keyes;T. Fortin;B. Pappas
中科院分区：
文献类型：
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作者：
Steffany A. L. Bennett;M. Tenniswood;Jiahua Chen;C. M. Davidson;M. T. Keyes;T. Fortin;B. Pappas
与衰老和进行性神经退行性疾病相关的脑血流量的慢性减少可加速认知功能衰竭。为了评估慢性脑血管功能不全是否诱发神经元凋亡，在永久性颈动脉闭塞的大鼠模型中定量海马中的凋亡性细胞死亡。双侧颈动脉阻断（2VO）显示，诱导海马神经元凋亡形态和DNA链断裂后2和27周结扎。慢性（27周）时间点的锥体细胞凋亡率高于亚慢性（2周）时间点。2VO诱导的细胞凋亡导致27周时锥体细胞总数减少，但在更早的时间点则没有，表明神经元逐渐丢失。旋臂迷宫中的工作和参考记忆错误与CA 1锥体细胞野中的凋亡神经元数量密切相关，但与CA 3锥体细胞野中的凋亡神经元数量无关。这些数据提供了第一个迹象表明，锥体神经元的凋亡损失可能在与慢性脑血管功能不全的临床条件相关的记忆障碍中发挥作用。
CHRONIC reductions in cerebral blood flow associated with aging and progressive neurodegenerative disorders can precipitate cognitive failure. To assess whether chronic cerebrovascular insufficiency elicits neuronal apoptosis, apoptotic cell death in the hippocampus was quantitated in a rat model of permanent carotid occlusion. Bilateral carotid artery occlusion (2VO) was shown to induce apoptotic morphology and DNA strand breaks in hippocampal neurons 2 and 27 weeks after ligation. The rate of pyramidal cell apoptosis was higher at chronic (27 weeks) compared to sub-chronic (2 weeks) time points. 2VO-induced apoptosis resulted in a decrease in total pyramidal cell number at 27 weeks but not at earlier time points, indicating progressive neuronal loss. Working and reference memory errors in the radial arm maze were strongly correlated with the number of apoptotic neurons in CA1 but not CA3 pyramidal cell fields. These data provide the first indication that apoptotic loss of pyramidal neurons may play a role in memory impairment associated with clinical conditions of chronic cerebrovascular insufficiency.