GENETIC AND HISTOLOGIC EVIDENCE IMPLICATES ROLE OF INFLAMMATION IN TRAUMATIC BRAIN INJURY-INDUCED APOPTOSIS IN THE RAT CEREBRAL CORTEX FOLLOWING MODERATE FLUID PERCUSSION INJURY
GENETIC AND HISTOLOGIC EVIDENCE IMPLICATES ROLE OF INFLAMMATION IN TRAUMATIC BRAIN INJURY-INDUCED APOPTOSIS IN THE RAT CEREBRAL CORTEX FOLLOWING MODERATE FLUID PERCUSSION INJURY
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DOI：
10.1016/j.neuroscience.2010.10.018
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发表时间：
2010-12-29
期刊：
影响因子：
3.3
通讯作者：
Borlongan, C. V.
中科院分区：
文献类型：
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作者：
Shojo, H.;Kaneko, Y.;Borlongan, C. V.
创伤性脑损伤（TBI）导致大面积脑损伤然而，在损伤后具有多种机制的继发性损伤和事件的时间顺序尚未阐明。在此，我们检查了TBI脑中细胞凋亡的发生以及炎症和细胞凋亡之间的因果关系。微阵列分析检测到凋亡相关基因表达水平的明显变化，其揭示了外侧皮质中23种基因的时间依赖性表达模式。上调的23种基因包括炎性细胞因子如白细胞介素1（IL 1）α，IL 1 β，肿瘤坏死因子（TNF）时间依赖性基因表达谱分析表明，炎症后细胞凋亡随后被诱导。这些结果共同表明，凋亡相关基因表达的变化可能与炎症反应有关。以细胞色素c渗漏到细胞质中、DNA断裂和TBI脑中受影响半球Caspase-3阳性细胞的外侧皮质中的凋亡细胞为特征的凋亡在3小时后最初是零星的，但这些凋亡细胞随后在6和12小时增加并聚集在大脑皮质中，并在48小时逐渐达到平台期。有趣的是，CD 68巨噬细胞标记的细胞的表达谱与TBI后凋亡细胞的表达谱非常相似，包括炎性信号传导途径在凋亡细胞死亡进程中的作用。这些结果共同表明TBI诱导凋亡相关基因的上调，伴随着在损伤后3-48小时期间凋亡脑病理学的检测，这可能是由炎症介导的。当在亚急性TBI阶段启动时，设计用于消除细胞凋亡和/或炎症的药物可以证明是有效的（C）2010 IBRO由爱思唯尔有限公司出版版权所有
Traumatic brain injury (TBI) causes massive brain damage However, the secondary injury and temporal sequence of events with multiple mechanisms after the insult has not been elucidated Here we examined the occurrence of apoptosis and a causal relationship between inflammation and apoptosis in the TBI brain Following a lateral moderate fluid percussion injury model of TBI in adult rats, microarray analyses detected apparent changes in the expression levels of apoptosis related genes which revealed time-dependent expression patterns for 23 genes in the lateral cortex The upregulated 23 genes included inflammatory cytokines such as interleukin 1 (IL 1) alpha, IL 1 beta, and tumor necrotic factor (TNF) which immediately increased at 3 h following the injury Time dependent gene expression profile analyses showed that apoptosis was subsequently induced following inflammation These results taken together suggested changes in expression of apoptosis related genes may be associated with inflammatory response Accompanying this surge of cell death genes after TBI was a neurostructural pathologic hall mark of apoptosis characterized by leakage of cytochrome c into cytoplasm, DNA fragmentation and apoptotic cells in the lateral cortex of the impacted hemisphere Caspase-3 positive cells in the TBI brain were initially sporadic after 3 h, but these apoptotic cells subsequently increased and populated the cerebral cortex at 6 and 12 h, and gradually reached a plateau by 48 h Interestingly, the expression profile of CD68 macrophage labeled cells closely resembled that of apoptotic cells after TBI, including the role of inflammatory signaling pathway in the progression of apoptotic cell death These results taken together suggest that TBI induced upregulation of apoptosis related genes, concomitant with the detection of apoptotic brain pathology during the 3-48 h post-injury period, which may be likely mediated by inflammation Thera pies designed at abrogating apoptosis and/or inflammation may prove effective when initiated at this subacute TBI phase (C) 2010 IBRO Published by Elsevier Ltd All rights reserved