Abstract
Mild traumatic brain injuries can have long-term consequences that interfere with the life of the patient and impose a burden on our health care system. Oxidative stress has been identified as a contributing factor for the progression of neurodegeneration following TBI. A major source of oxidative stress for many veterans is cigarette smoking and second-hand smoke, which has been shown to have an effect on TBI recovery. To examine the potential influences of second-hand smoke during recovery from TBI, we utilized a mouse model of closed head injury, followed by repeated exposure to cigarette smoke and treatment with a neuroprotective antioxidant. We found that neither the mild injuries nor the smoke exposure produced axonal damage detectable with amino cupric silver staining. However, complexity in the dendritic arbors was significantly reduced after mild TBI plus smoke exposure. In the hippocampus, there were astrocytic responses, including Cyp2e1 upregulation, after the injury and tobacco smoke insult. This study provides useful context for the importance of lifestyle changes, such as reducing or eliminating cigarette smoking, during recovery from TBI.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank Andrea Smith and Tai Vo for expert animal assistance, Miseanne Tang for technical assistance, and Dr. John C. M. Tsibris for the loan of the smoking system.
Funding
This study was supported by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development (I01RX001520)), the Assistant Secretary of Defense for Health Affairs through the Congressionally Directed Gulf War Illness Research Program (W81XWH-16–1-0626), the Florida Department of Health James and Esther King Biomedical Research Program (4KB14), and The Bay Pines Foundation. The funding sources had no involvement in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
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WAR performed animal experiments, analyzed and interpreted the data, created figures, and wrote the manuscript. JNS conceived and performed the experiments. KLK and DCD performed animal experiments and data analysis. KEM performed data analysis and interpretation. MO assisted with experiments related to the use of the smoking machine. RFM performed the Golgi staining and dendritic analysis. VD analyzed and interpreted data and contributed significantly to the writing to the manuscript. BAC conceived the studies, analyzed data, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
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The authors declare no competing interests. The contents do not represent the views of the Department of Veterans Affairs or the US Government and the opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.
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The animal protocol was approved by the Bay Pines VA Institutional Animal Care and Use Committee (IACUC) and performed in accordance with all institutional, agency, and governmental Animal Welfare Regulations.
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Ratliff, W.A., Saykally, J.N., Keeley, K.L. et al. Sidestream Smoke Affects Dendritic Complexity and Astrocytes After Model Mild Closed Head Traumatic Brain Injury. Cell Mol Neurobiol 42, 1453–1463 (2022). https://doi.org/10.1007/s10571-020-01036-5
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DOI: https://doi.org/10.1007/s10571-020-01036-5