Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal degeneration and early induction of transcription factor genes in the hippocampus
Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal degeneration and early induction of transcription factor genes in the hippocampus
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DOI：
10.1016/s0169-328x(98)00298-8
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发表时间：
1999-03-05
期刊：
影响因子：
--
通讯作者：
Gass, P
中科院分区：
文献类型：
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作者：
Böttiger, BW;Teschendorf, P;Gass, P
为了分析特定基因和蛋白质在全脑缺血后神经元信号级联中的作用，在小鼠中建立可重复的全脑缺血模型将是有用的，该模型可能允许研究具有特定基因组突变的小鼠。我们首先报告了小鼠可逆性心脏循环骤停模型的开发，以及这种损伤对海马神经元变性和立即早期基因（IEG）表达的影响。通过机械通气 NMRI 小鼠的心室颤动诱导 5 分钟的心脏循环骤停。成功心肺复苏 (CPR) 后，动物被允许自发再灌注 3 小时 (n = 7) 和 7 天 (n = 7)。 TUNEL 染色显示第 7 天时海马 CA1 区的一部分神经元发生选择性变性。大约 30% 的 TUNEL 阳性细胞核显示染色质浓缩和凋亡小体。 3 小时时进行的 IEG 表达免疫组织化学研究显示，海马体所有区域中 c-Fos、c-Jun 和 Krox-24 蛋白均显着诱导，在脆弱的 CA1 锥体神经元和齿状回中达到峰值。相反，与未经治疗的对照动物 (n = 3) 相比，假手术动物 (n = 3) 没有表现出海马神经元变性或 IEG 表达增加。总之，我们提出了一种利用完全心循环骤停和随后的心肺复苏的小鼠全脑缺血和再灌注的新模型。缺血 5 分钟后，一部分 CAI 锥体神经元在 7 天时呈 TUNEL 阳性。在海马体的所有部分都观察到 IEG 的表达，包括选择性脆弱的 CA1 锥体神经元。这似乎是一个很好的模型，可用于评估转基因和基因敲除小鼠整体缺血后各种基因的作用。 (C) 1999 Elsevier Science B.V. 保留所有权利。
To analyze the role of specific genes and proteins in neuronal signaling cascades following global cerebral ischemia, it would be useful to have a reproducible model of global cerebral ischemia in mice that potentially allows the investigation of mice with specific genomic mutations. We first report on the development of a model of reversible cardiocirculatory arrest in mice and the consequences of such an insult to neuronal degeneration and expression of immediate early genes (IEG) in the hippocampus. Cardiocirculatory arrest of 5 min duration was induced via ventricular fibrillation in mechanically ventilated NMRI mice. After successful cardiopulmonary resuscitation (CPR), animals were allowed to reperfuse spontaneously for 3 h (n = 7) and 7 days (n = 7). TUNEL staining revealed a selective degeneration of a subset of neurons in the hippocampal CA1 sector at 7 days. About 30% of all TUNEL-positive nuclei showed condensed chromatin and apoptotic bodies. Immunohistochemical studies of IEG expression performed at 3 h exhibited a marked induction of c-Fos, c-Jun, and Krox-24 protein in all sectors of the hippocampus, peaking in vulnerable CA1 pyramidal neurons and in dentate gyrus. In contrast, sham-operated animals (n = 3) did not reveal neuronal degeneration or increased IEG expression in the hippocampus when compared with untreated control animals (n = 3). In conclusion, we present a new model of global cerebral ischemia and reperfusion in mice with the use of complete cardiocirculatory arrest and subsequent CPR. Following 5 min of ischemia, a subset of CAI pyramidal neurons was TUNEL-positive at 7 days. The expression of IEG was observed in all sectors of the hippocampus, including selectively vulnerable CA1 pyramidal neurons. This appears to be a good model which should be useful in evaluating the role of various genes in transgenic and knockout mice following global ischemia. (C) 1999 Elsevier Science B.V. All rights reserved.