Increases in tumor necrosis factor-α following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampus
Increases in tumor necrosis factor-α following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampus
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DOI：
10.1111/j.1471-4159.2005.03163.x
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发表时间：
2005-06-01
影响因子：
4.7
通讯作者：
Seishima, M
中科院分区：
文献类型：
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作者：
Murakami, Y;Saito, K;Seishima, M
评估了脑内常驻脑细胞和骨髓源性细胞在短暂性全脑缺血后产生的肿瘤坏死因子- α (tnf - α)的作用。野生型小鼠（C57Bl/6J）双侧颈总动脉闭塞（BCCAo）缺血20 min后，海马中tnf - α mRNA表达水平在3 h和36 h显著升高，呈双相表达模式。野生型骨髓移植（BMT）嵌合- tnf - α基因缺陷小鼠（T/W）和tnf - α基因缺陷小鼠(BMT - tnf - α基因缺陷小鼠（T/T）在早期时间点均无海马tnf - α mRNA表达水平，尽管T/W BMT小鼠在36 h时可检测到tnf - α mRNA水平。组织病理学结果显示，野生型和tnf - α基因缺陷小鼠在短暂缺血后4天和7天各组间无差异。此外，核因子- κ B （nf - κ B）在全脑缺血后12小时内被激活，但电泳迁移迁移试验（EMSA）显示野生型和tnf - α基因缺陷小鼠之间没有组间差异。综上所述，早期海马tnf - α mRNA表达可能与骨髓源性细胞无关，早在缺血后36 h的继发性tnf - α表达可能主要来自内源性脑细胞，也可能是少数骨髓源性细胞。虽然我们不能排除tnf - α参与短暂性全脑缺血后海马生理变化的可能性，但这些结果表明，在我们的研究条件下，tnf - α不影响海马神经元的形态变化。
The actions of tumor necrosis factor-alpha (TNF-alpha) produced by resident brain cells and bone marrow-derived cells in brain following a transient global ischemia were evaluated. In wild-type mice (C57Bl/6J) following 20 min ischemia with bilateral common carotid artery occlusion (BCCAo), TNF-alpha mRNA expression levels in the hippocampus were significantly increased at 3 h and 36 h and exhibited a biphasic expression pattern. There were no hippocampal TNF-alpha mRNA expression levels at early time points in either wild-type mice bone marrow transplanted (BMT)-chimeric-TNF-alpha gene-deficient (T/W) or TNF-alpha gene-deficient mice BMT-TNF-alpha gene-deficient mice (T/T), although TNF-alpha mRNA levels were detectable in T/W BMT mice at 36 h. Histopathological findings showed no intergroup differences between wild-type and TNF-alpha gene-deficient mice at 4 and 7 days after transient ischemia. In addition, nuclear factor-kappa B (NF-kappa B) was activated within 12 h after global cerebral ischemia, but electrophoretic mobility shift assays (EMSA) showed no intergroup differences between wild type and TNF-alpha gene-deficient mice. In summary, early hippocampal TNF-alpha mRNA expression may not be related to bone marrow-derived cells, and secondary TNF-alpha expression as early as 36 h after ischemia probably resulted mainly from endogenous brain cells and possibly a few bone marrow-derived cells. Although we cannot exclude the possibility of the TNF-alpha contribution to the physiologic changes of hippocampus after transient global ischemia, these results indicate that TNF-alpha does not influence the morphological changes of the hippocampal neurons under our study condition.