Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation
Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation
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DOI：
10.1016/j.neulet.2004.11.051
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发表时间：
2005-03-16
影响因子：
2.5
通讯作者：
Neumar, RW
中科院分区：
文献类型：
--
作者：
Chen, ZM;Kontonotas, D;Neumar, RW
半胱天冬酶激活发生在短暂前脑缺血后的成年大鼠脑离散细胞群再灌注1小时内。基于这些细胞接近成年神经发生区域和已知的发育中神经元对凋亡的敏感性，我们测试了在未成熟神经元或神经祖细胞中快速触发缺血后半胱天冬酶激活的假设。成年雄性Long Evans大鼠注射BrdU标记有丝分裂细胞1，7，或28天前进行研究。然后对大鼠进行假手术或10分钟短暂前脑缺血。在再灌注后1小时，大鼠进行灌注固定和大脑制备免疫组织化学分析。半胱天冬酶-底物裂解的免疫标记，使用针对α-血影蛋白的半胱天冬酶衍生片段的抗体，在喙齿状回、背侧纹状体、极端旁正中CA 1海马体、神经膜、嗅结节和丘脑的离散细胞群中观察到。在BrdU注射后的任何时间点，没有细胞被半胱天冬酶底物裂解和BrdU双标记。此外，免疫标记的半胱天冬酶底物裂解细胞没有双重标记的标记物的未成熟神经元（doublecortin）或祖细胞（巢蛋白），但双重标记的成熟神经元标记NeuN。这些结果表明，在成年大鼠脑短暂前脑缺血后快速触发caspase激活的现象是特定的成熟神经元，而不发生在神经祖细胞或未成熟的神经元。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Caspase activation occurs within 1 h of reperfusion in discrete cell populations of the adult rat brain following transient forebrain ischemia. Based on the proximity of these cells to regions of adult neurogenesis and the known susceptibility of developing neurons to apoptosis, we tested the hypothesis that rapidly triggered post-ischemic caspase activation occurs in immature neurons or neuroprogenitor cells. Adult male Long Evans rats were injected with BrdU to label mitotic cells 1, 7, or 28 days prior to being studied. Rats were then subjected to either sham surgery or 10-min transient forebrain ischemia. At 1 h after reperfusion, rats underwent perfusion fixation and brains prepared for immunohistochemical analysis. Immunolabeling for caspase-substrate cleavage, using an antibody directed at the caspase derived fragment of alpha-spectrin, was observed in discrete cell populations of the rostral dentate gyrus, dorsal striatum, extreme paramedian CA1 hippocampus, indusium gresium, olfactory tubercle, and thalamus. No cells double-labeled for caspase-substrate cleavage and BrdU at any time point after BrdU injection. Furthermore, cells immunolabeled for caspase-substrate cleavage did not double-label for markers of immature neurons (doublecortin) or progenitor cells (nestin), but did double-label for the mature neuronal marker NeuN. These results indicate that the phenomenon of rapidly triggered caspase activation in the adult rat brain after transient forebrain ischemia is specific to mature neurons and does not occur in neuroprogenitor cells or immature neurons. (C) 2004 Elsevier Ireland Ltd. All rights reserved.