Delayed genomic responses to transient middle cerebral artery occlusion in the rat

被引:52
作者
Kim, JB
Piao, CS
Lee, KW
Han, PL
Ahn, JI
Lee, YS
Lee, JK
机构
[1] Inha Univ, Sch Med, Dept Anat, Inchon 400712, South Korea
[2] Ewha Womans Univ, Sch Med, Dept Neurosci & EIN, Seoul, South Korea
[3] Hanyang Univ, Sch Med, Dept Biochem, Seoul 133791, South Korea
关键词
delayed neuronal death; focal ischemia; gene expression; microarray;
D O I
10.1111/j.1471-4159.2004.02429.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ischemic stress in the brain induces acute and massive neuronal death in the targeted area, which is followed by a second round of detrimental processes, called delayed neuronal death, in the neighboring areas. To test the hypothesis that transcriptional control plays a role in the pathophysiology of the postischemic brain, the genomic responses that occurred in the brain at 3, 6 and, 12 h, and 1, 2 or 4 days after transient middle cerebral artery occlusion (MCAO) were examined using a microarray harboring 5000 rat cDNAs. This analysis indicated that the number of up-regulated genes was gradually increased, along with the concomitant reduction in the number of down-regulated genes, until 12 h to 1 day after MCAO. It was followed by a delayed surge of down-regulated genes at 2 days after MCAO. Northern blots and immunohistological analysis confirmed the validity of these microarray data. We present a list of 85 genes that were up-regulated more than 2.3-fold between 12 h and 4 days after MCAO, which included 56 novel genes whose expression has not previously been implicated in ischemic pathophysiology. The list included genes involved in oxidative stress, inflammation, extracellular matrix (ECM), neuronal development and differentiation processes. Together these results suggest that the pathophysiology of the postischemic brain proceeds by the transcriptional activation of genes related to the process of delayed neuronal damage and/or recovery and repair.
引用
收藏
页码:1271 / 1282
页数:12
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