Blast-induced traumatic brain injury (bTBI) is one of the major causes of persistent disabilities in Service Members, and a history of bTBI has been identified as a primary risk factor for developing age-associated neurodegenerative diseases. Clinical observations of several military blast casualties have revealed a rapid age-related loss of white matter integrity in the brain. In the present study, we have tested the effect of single and tightly coupled repeated blasts on cellular senescence in the rat brain. Isoflurane-anesthetized rats were exposed to either a single or 2 closely coupled blasts in an advanced blast simulator. Rats were euthanized and brains were collected at 24 h, 1 month and 1 year post-blast to determine senescence-associated-β-galactosidase (SA-β-gal) activity in the cells using senescence marker stain. Single and repeated blast exposures resulted in significantly increased senescence marker staining in several neuroanatomical structures, including cortex, auditory cortex, dorsal lateral thalamic nucleus, geniculate nucleus, superior colliculus, ventral thalamic nucleus and hippocampus. In general, the increases in SA-β-gal activity were more pronounced at 1 month than at 24 h or 1 year post-blast and were also greater after repeated than single blast exposures. Real-time quantitative RT-PCR analysis revealed decreased levels of mRNA for senescence marker protein-30 (SMP-30) and increased mRNA levels for p21 (cyclin dependent kinase inhibitor 1A, CDKN1A), two other related protein markers of cellular senescence. The increased senescence observed in some of these affected brain structures may be implicated in several long-term sequelae after exposure to blast, including memory disruptions and impairments in movement, auditory and ocular functions.

中文翻译：

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爆炸暴露会导致大鼠脑部细胞衰老加速。

爆炸引起的颅脑外伤（bTBI）是服务成员持续残疾的主要原因之一，并且bTBI的历史已被确定为发展与年龄相关的神经退行性疾病的主要危险因素。对数起军事爆炸伤亡的临床观察表明，大脑中与年龄相关的白质完整性迅速丧失。在本研究中，我们测试了单次紧密耦合的反复爆炸对大鼠脑细胞衰老的影响。异氟烷麻醉的大鼠在高级爆炸模拟器中暴露于单个或两个紧密耦合的爆炸中。对大鼠实施安乐死并在爆炸后24小时，1个月和1年收集大脑，以使用衰老标记染色确定细胞中与衰老相关的β-半乳糖苷酶（SA-β-gal）活性。一次和多次爆炸暴露导致多个神经解剖结构，包括皮质，听觉皮层，丘脑背外侧核，膝状核，上丘，腹侧丘脑核和海马体的衰老标记染色显着增加。通常，SA-β-gal活性的增加在爆炸后1小时比在爆炸后24小时或1年更明显，并且在重复后也比单次爆炸暴露更大。实时定量RT-PCR分析显示，衰老标记蛋白-30（SMP-30）的mRNA水平降低，而细胞衰老的两个其他相关蛋白标记p21（细胞周期蛋白依赖性激酶抑制剂1A，CDKN1A）的mRNA水平升高。