Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury
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...
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| Format: | Article |
| Language: | English |
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Mary Ann Liebert
2024-01-01
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| Series: | Neurotrauma Reports |
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| Online Access: | https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0107 |
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| author | Andrew R. Morris Erwin K. Gudenschwager Basso Miguel A. Gutierrez-Monreal Rawad Daniel Arja Firas H. Kobeissy Christopher G. Janus Kevin K.W. Wang Jiepei Zhu Andrew C. Liu |
| author_facet | Andrew R. Morris Erwin K. Gudenschwager Basso Miguel A. Gutierrez-Monreal Rawad Daniel Arja Firas H. Kobeissy Christopher G. Janus Kevin K.W. Wang Jiepei Zhu Andrew C. Liu |
| author_sort | Andrew R. Morris |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:27:52Z |
| format | Article |
| id | doaj.art-6fa9a64e6be145d29975a658164a9eaf |
| institution | Directory Open Access Journal |
| issn | 2689-288X |
| language | English |
| last_indexed | 2024-03-08T11:27:52Z |
| publishDate | 2024-01-01 |
| publisher | Mary Ann Liebert |
| record_format | Article |
| series | Neurotrauma Reports |
| spelling | doaj.art-6fa9a64e6be145d29975a658164a9eaf2024-01-26T04:45:58ZengMary Ann LiebertNeurotrauma Reports2689-288X2024-01-0151617310.1089/NEUR.2023.0107Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain InjuryAndrew R. MorrisErwin K. Gudenschwager BassoMiguel A. Gutierrez-MonrealRawad Daniel ArjaFiras H. KobeissyChristopher G. JanusKevin K.W. WangJiepei ZhuAndrew C. LiuChronic 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.https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0107chronic brain injurycircadian rhythmmidline fluid percussion injury (mFPI)PiezoSleepsleep/wake disturbancestraumatic brain injury (TBI) |
| spellingShingle | Andrew R. Morris Erwin K. Gudenschwager Basso Miguel A. Gutierrez-Monreal Rawad Daniel Arja Firas H. Kobeissy Christopher G. Janus Kevin K.W. Wang Jiepei Zhu Andrew C. Liu Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury Neurotrauma Reports chronic brain injury circadian rhythm midline fluid percussion injury (mFPI) PiezoSleep sleep/wake disturbances traumatic brain injury (TBI) |
| title | Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury |
| title_full | Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury |
| title_fullStr | Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury |
| title_full_unstemmed | Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury |
| title_short | Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury |
| title_sort | lifelong chronic sleep disruption in a mouse model of traumatic brain injury |
| topic | chronic brain injury circadian rhythm midline fluid percussion injury (mFPI) PiezoSleep sleep/wake disturbances traumatic brain injury (TBI) |
| url | https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0107 |
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