Mild as well as severe insults produce necrotic, not apoptotic, cells: Evidence from 60-min seizures
Mild as well as severe insults produce necrotic, not apoptotic, cells: Evidence from 60-min seizures
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DOI：
10.1016/j.neulet.2009.12.022
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发表时间：
2010-01-29
影响因子：
2.5
通讯作者：
Allen, Suni G.
中科院分区：
文献类型：
--
作者：
Fujikawa, Denson G.;Zhao, Shuangping;Allen, Suni G.
我们测试的假设，轻度侮辱产生凋亡，和严重的侮辱坏死，细胞进行成年Wistar大鼠60分钟，而不是3小时的全身性癫痫发作。6和24小时后，通过光镜和电子显微镜检查，TUNEL染色和活性caspase-3免疫反应性的存在，以及癫痫发作后24小时的DNA梯状化的证据，对大鼠的大脑进行评估。来自出生后第8天大鼠幼崽的压后皮质的凋亡神经元作为阳性对照。癫痫发作后6 h和24 h，分别有16个和15个脑区出现明显的嗜酸性神经元。癫痫发作后24 h，三个脑区有大量TUNEL阳性神经元。caspase-3免疫反应阴性。电镜下嗜酸神经元坏死。超微结构上，它们萎缩，电子致密，萎缩，核固缩，线粒体肿胀，嵴断裂。细胞核不包含不规则的染色质团块后发现3小时癫痫发作。在超微结构上研究的6个脑区中，没有一个在3小时癫痫发作后24小时显示DNA梯状，在60分钟癫痫发作后24小时显示DNA梯状，这可能是因为受损的神经元太少，尽管缺乏染色质聚集可能是一个促成因素。癫痫发作后，轻度和重度损伤均产生caspase-3阴性坏死神经元。这些结果不支持轻度损伤产生凋亡和重度损伤产生坏死细胞的假设。出版社：Elsevier爱尔兰Ltd.
We tested the hypothesis that mild insults produce apoptotic, and severe insults necrotic, cells by subjecting adult Wistar rats to 60-min instead of 3-h generalized seizures. Rats' brains were evaluated 6 and 24 h later for evidence of neuronal necrosis by light and electron microscopy, the presence of TUNEL staining and active caspase-3 immunoreactivity, and for evidence of DNA laddering 24 h after seizures. Apoptotic neurons from the retrosplenial cortex of postnatal day 8 rat pups served as positive controls. Six and 24 h after seizures, 16 and 15 brain regions respectively out of 24 showed significant numbers of acidophilic neurons by hematoxylin and eosin stain. Three brain regions had significant numbers of TUNEL-positive neurons 24 h after seizures. No neurons showed active caspase-3 immunoreactivity. Acidophilic neurons were necrotic by electron-microscopic examination. Ultrastructurally, they were shrunken and electron-dense, with shrunken, pyknotic nuclei and swollen mitochondria with disrupted cristae. Nuclei did not contain the irregular chromatin clumps found after 3-h seizures. None of the six brain regions studied ultrastructurally that show DNA laddering 24 h after 3-h seizures showed DNA laddering 24 h after 60-min seizures, probably because there were too few damaged neurons, although the lack of chromatin clumping might have been a contributing factor. Following seizures, a mild as well as a severe insult produces caspase-3-negative necrotic neurons. These results do not support the hypothesis that mild insults produce apoptotic, and severe insults, necrotic, cells. Published by Elsevier Ireland Ltd.