The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen
The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen
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DOI：
10.1016/j.brainres.2006.10.077
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发表时间：
2007-01-26
期刊：
影响因子：
2.9
通讯作者：
Sakabe, Takefumi
中科院分区：
文献类型：
--
作者：
Hirata, Takao;Cui, Ying Jun;Sakabe, Takefumi
已有报道，缺血前反复高压氧（HBO）暴露可提供针对缺血性脑损伤的神经保护。本研究观察了高压氧（3.5大气压，100%氧气，1小时，连续5天）对大鼠神经保护作用的时程和基因/蛋白表达的变化。首先，在HBO治疗后6 h、12 h、24 h和72 h，对大鼠进行前脑缺血（8 min）。缺血7 d后取海马CA 1区神经元进行组织学检查。第二，时间基因组反应和蛋白质表达进行了检查，在相同的时间点后，高压氧会议没有使动物缺血。当最后一次HBO治疗时间为缺血前6 h、12 h或24 h时，HBO显著减少了通常在短暂性前脑缺血后海马CA 1区神经元的丢失（存活神经元分别为55%、75%和53%），而如果缺血前延迟72 h，HBO则没有保护作用（存活神经元仅为6%）。对微阵列数据的统计分析显示，包括7个注释基因（p75（NTR），C/EBP delta，CD 74，Edq 2，Trip 10，Nrp 1和Igf 2）在内的60个探针组的显著上调，其时间过程表达对应于HBO诱导的神经保护作用。p75（NTR）、C/EBP δ和CD 74的蛋白水平显著升高（最大倍数变化分别为2.9、2.0和7.9）。结果提示，HBO诱导的脑保护作用存在时间窗，在6、12、24 h有保护作用，而在72 h无保护作用。虽然确切的相互作用有待确定，但与神经营养因子和炎症免疫系统相关的基因/蛋白可能参与HBO诱导的神经保护。(c)2006 Elsevier B. V.保留所有权利。
Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24h before ischemia (survived neurons 55%,75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75(NTR), C/EBP delta, CD74, Edq2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75(NTR), C/EBP delta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection. (c) 2006 Elsevier B.V. All rights reserved.