Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation
BackgroundTraumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI.MethodsA total of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1292014/full |
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| author | Ziyuan Chen Pengfei Wang Hao Cheng Ning Wang Mingzhe Wu Ziwei Wang Zhi Wang Wenwen Dong Dawei Guan Linlin Wang Rui Zhao Rui Zhao Rui Zhao |
| author_facet | Ziyuan Chen Pengfei Wang Hao Cheng Ning Wang Mingzhe Wu Ziwei Wang Zhi Wang Wenwen Dong Dawei Guan Linlin Wang Rui Zhao Rui Zhao Rui Zhao |
| author_sort | Ziyuan Chen |
| collection | DOAJ |
| description | BackgroundTraumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI.MethodsA total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis.ResultsThe adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1β and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi.ConclusionAdolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction. |
| first_indexed | 2024-03-11T15:55:49Z |
| format | Article |
| id | doaj.art-5504331070184bd5a3e4f9d7e2f437e4 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-11T15:55:49Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-5504331070184bd5a3e4f9d7e2f437e42023-10-25T10:41:57ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-10-011710.3389/fnins.2023.12920141292014Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammationZiyuan Chen0Pengfei Wang1Hao Cheng2Ning Wang3Mingzhe Wu4Ziwei Wang5Zhi Wang6Wenwen Dong7Dawei Guan8Linlin Wang9Rui Zhao10Rui Zhao11Rui Zhao12Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaDepartment of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, ChinaLiaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang, ChinaBackgroundTraumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI.MethodsA total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis.ResultsThe adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1β and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi.ConclusionAdolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction.https://www.frontiersin.org/articles/10.3389/fnins.2023.1292014/fulltraumatic brain injuryanxiety and depressioncognitive dysfunctionneuroinflammationoxidative stress |
| spellingShingle | Ziyuan Chen Pengfei Wang Hao Cheng Ning Wang Mingzhe Wu Ziwei Wang Zhi Wang Wenwen Dong Dawei Guan Linlin Wang Rui Zhao Rui Zhao Rui Zhao Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation Frontiers in Neuroscience traumatic brain injury anxiety and depression cognitive dysfunction neuroinflammation oxidative stress |
| title | Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation |
| title_full | Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation |
| title_fullStr | Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation |
| title_full_unstemmed | Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation |
| title_short | Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation |
| title_sort | adolescent traumatic brain injury leads to incremental neural impairment in middle aged mice role of persistent oxidative stress and neuroinflammation |
| topic | traumatic brain injury anxiety and depression cognitive dysfunction neuroinflammation oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1292014/full |
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