Penetrating Ballistic Brain Injury Produces Acute Alterations in Sleep and Circadian-Related Genes in the Rodent Cortex: A Preliminary Study.

Penetrating Ballistic Brain Injury Produces Acute Alterations in Sleep and Circadian-Related Genes in the Rodent Cortex: A Preliminary Study.
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DOI:
10.3389/fneur.2021.745330
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发表时间:
2021
影响因子:
3.4
通讯作者:
Haghighi F
Haghighi F
中科院分区:
医学3区
文献类型:
--
作者:
Mountney A;Blaze J;Wang Z;Umali M;Flerlage WJ;Dougherty J;Ge Y;Shear D;Haghighi F

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创伤性脑损伤(TBI)每年影响数百万美国人,在退伍军人社区中患病率极高,睡眠障碍是最常见的症状之一。睡眠质量和数量的减少会对恢复产生负面影响,并导致广泛的行为和生理症状,如认知受损,情绪和焦虑症以及心血管影响。因此,为了改善患者的长期预后并开发新的治疗方法,了解TBI后睡眠障碍的分子机制至关重要。在这项工作中,我们进行了转录分析,在一个既定的啮齿动物模型的穿透弹道脑损伤(PBBI)结合连续睡眠/清醒EEG/EMG记录的第一个24小时后受伤。PBBI大鼠在睡眠结构方面表现出深刻的差异。与假手术对照组动物相比,受伤的动物在慢波睡眠中花费了更多的时间,而在REM睡眠中花费的时间更少。为了鉴定PBBI相关的转录差异,我们随后在损伤后24小时进行了全转录组基因表达谱分析,其鉴定了大量在损伤的皮质中差异表达的免疫相关基因以及睡眠相关基因。此外,还鉴定了与在各个睡眠阶段花费的总时间相关的转录变化。这种分子变化可能是TBI后出现的病理和症状的基础,包括神经变性、睡眠障碍和情绪障碍。
Traumatic brain injury (TBI) affects millions of Americans each year, with extremely high prevalence in the Veteran community, and sleep disturbance is one of the most commonly reported symptoms. Reduction in the quality and amount of sleep can negatively impact recovery and result in a wide range of behavioral and physiological symptoms, such as impaired cognition, mood and anxiety disorders, and cardiovascular effects. Thus, to improve long-term patient outcomes and develop novel treatments, it is essential to understand the molecular mechanisms involved in sleep disturbance following TBI. In this effort, we performed transcriptional profiling in an established rodent model of penetrating ballistic brain injury (PBBI) in conjunction with continuous sleep/wake EEG/EMG recording of the first 24 h after injury. Rats subjected to PBBI showed profound differences in sleep architecture. Injured animals spent significantly more time in slow wave sleep and less time in REM sleep compared to sham control animals. To identify PBBI-related transcriptional differences, we then performed transcriptome-wide gene expression profiling at 24 h post-injury, which identified a vast array of immune- related genes differentially expressed in the injured cortex as well as sleep-related genes. Further, transcriptional changes associated with total time spent in various sleep stages were identified. Such molecular changes may underlie the pathology and symptoms that emerge following TBI, including neurodegeneration, sleep disturbance, and mood disorders.
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发表时间: 2017-04-10
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