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培养的小胶质细胞对模拟爆炸超压的基因表达改变:脉冲持续时间的可能作用。

Altered gene expression in cultured microglia in response to simulated blast overpressure: possible role of pulse duration.

机构信息

Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USA.

出版信息

Neurosci Lett. 2012 Jul 26;522(1):47-51. doi: 10.1016/j.neulet.2012.06.012. Epub 2012 Jun 12.

Abstract

Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to "isolate" the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15 to 45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.

摘要

爆炸超压早已被证实会对肺部和中耳等含气器官造成气压伤。然而,在伊拉克和阿富汗的经验表明,即使没有明显的外部损伤,接触爆炸弹药的个体也可能遭受创伤性脑损伤(TBI)。爆炸冲击波与完整颅腔中的大脑相互作用极其复杂,因此很难得出冲击波以直接方式与大脑相互作用造成损伤的结论。为了“隔离”冲击波并测试其对细胞的主要影响,我们在防爆室内使培养的小神经胶质细胞暴露于模拟的爆炸超压下。压力范围为 15 至 45 磅/平方英寸(psi),不会改变小神经胶质细胞 Cox-2 水平或 TNF-α 分泌,也不会导致细胞损伤。微阵列分析显示,与免疫功能和炎症反应相关的许多小神经胶质细胞基因的表达增加,包括 Saa3、Irg1、Fas 和 CxCl10。基因表达的所有变化都依赖于脉冲持续时间,而与压力无关。这些结果表明,爆炸超压会轻度激活小神经胶质细胞,并揭示了脉冲持续时间在这一过程中的一个以前未被记录的作用。

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