Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury.
Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury.
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DOI：
10.1089/neur.2023.0107
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发表时间：
2024
影响因子：
2.4
通讯作者：
Liu, Andrew C.
中科院分区：
文献类型：
--
作者：
Morris, Andrew R.;Gudenschwager Basso, Erwin K.;Gutierrez-Monreal, Miguel A.;Arja, Rawad Daniel;Kobeissy, Firas H.;Janus, Christopher G.;Wang, Kevin K. W.;Zhu, Jiepei;Liu, Andrew C.
关键词：
慢性睡眠/觉醒障碍（SWDs）与患者的创伤性脑损伤（TBI）密切相关，并且越来越被认识到。然而，其潜在的机制在很大程度上尚未得到充分的研究，因此迫切需要终身SWDs的动物模型。本研究的目的是建立慢性创伤性脑损伤啮齿动物模型，研究创伤性脑损伤对睡眠/觉醒行为的终身慢性影响。我们对4个月大的小鼠进行重复性中线液体冲击损伤（rmFPI），并使用无创PiezoSleep系统监测它们的睡眠/觉醒行为。受伤前记录睡眠/清醒状态（基线），之后每月记录一次。我们发现，创伤性脑损伤小鼠在光明期和黑暗期的睡眠时间都明显减少，从创伤性脑损伤后3个月开始，一直持续到整个研究过程。与睡眠表型一致，这些TBI小鼠表现出昼夜运动活动表型，并表现出减少的焦虑样行为。与假对照组相比，TBI小鼠体重增加更少，瘦质量和全身含水量也更少。此外，TBI小鼠表现出广泛的脑组织丢失，下丘脑和损伤附近的胶质纤维酸性蛋白和离子钙结合接头分子1水平升高，表明慢性神经病理。总之，我们的研究确定了TBI病理和相关的昼夜节律和睡眠/觉醒表型的关键时间窗。未来的研究应该利用这种小鼠模型来研究脑外伤后早期慢性睡眠/觉醒表型的分子机制。
Chronic sleep/wake disturbances (SWDs) are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong SWDs. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in 4-month-old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. Sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at 3 months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Further, TBI mice showed extensive brain tissue loss and increased glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 levels in the hypothalamus and vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes post-TBI early in life.
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影响因子：
5.9
作者：
Gangitano, Elena;Martinez-Sanchez, Noelia;Bellini, Maria Irene;Urciuoli, Irene;Monterisi, Stefania;Mariani, Stefania;Ray, David;Gnessi, Lucio
通讯作者：
Gnessi, Lucio
DOI：
10.1523/jneurosci.5103-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Greer JE;McGinn MJ;Povlishock JT
通讯作者：
Povlishock JT
影响因子：
2.4
作者：
Cantor, Joshua B.;Bushnik, Tamara;Spielman, Lisa A.
通讯作者：
Spielman, Lisa A.
影响因子：
12.7
作者：
Greer, John E.;Hanell, Anders;Povlishock, John T.
通讯作者：
Povlishock, John T.
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S