Global gene expression in the immature brain after hypoxia-ischemia

Global gene expression in the immature brain after hypoxia-ischemia
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DOI:
10.1097/01.wcb.0000141558.40491.75
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发表时间:
2004-12-01
影响因子:
6.3
通讯作者:
Hagberg, H
Hagberg, H
中科院分区:
医学1区
文献类型:
--
作者:
Hedtjarn, M;Mallard, C;Hagberg, H

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缺血诱导脑中差异表达基因的复杂反应。为了了解发育中大脑损伤的具体机制,获得新生儿缺氧缺血后转录组整体变化的信息非常重要。在本研究中,使用寡核苷酸阵列来研究在2、8、24小时的基因组变化。9日龄小鼠结扎左颈总动脉后缺氧(10%O-2)72 h。总之,343个基因差异表达的皮质,海马,丘脑和纹状体缺氧缺血后2至72小时,比较同侧与对侧半球和对照组,使用显着性分析的微阵列。共有283个基因表达上调,60个基因表达下调,其中94%的基因在新生儿缺氧缺血后未被发现。与转录因子和代谢相关的基因大多上调的转录本,而大多数下调的基因属于离子和囊泡运输和信号转导的类别。参与转录,应激和细胞凋亡的基因在损伤后早期被诱导,许多新的基因可能在新生儿缺氧缺血的病理生理学中起重要作用。
Ischemia induces a complex response of differentially expressed genes in the brain. In order to understand the specific mechanisms of injury in the developing brain, it is important to obtain information on global changes in the transcriptome after neonatal hypoxia-ischemia. In this study, oligonucleotide arrays were used to investigate genomic changes at 2, 8, 24. and 72 hours after neonatal hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia (10% O-2). In total, 343 genes were differentially expressed in cortex, hippocampus, thalamus, and striatum 2 to 72 hours after hypoxia-ischemia, when comparing ipsilateral with contralateral hemispheres and with controls, using the significance analysis for microarrays. A total of 283 genes were upregulated and 60 were downregulated, and 94% of the genes had not previously been shown after neonatal hypoxia-ischemia. Genes related to transcription factors and metabolism had mostly upregulated transcripts, whereas most downregulated genes belonged to the categories of ion and vesicular transport and signal transduction. Genes involved in transcription, stress, and apoptosis were induced early after the insult, and many new genes that may play important roles in the pathophysiology of neonatal hypoxia-ischemia were identified.