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Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury
Abstract
Physician-prescribed rest after traumatic brain injury (TBI) is both commonplace and an increasingly scrutinized approach to TBI treatment. Although this practice remains a standard of patient care for TBI, research of patient outcomes reveals little to no benefit of prescribed rest after TBI, and in some cases prolonged rest has been shown to interfere with patient well-being. In direct contrast to the clinical advice regarding physical activity after TBI, animal models of brain injury consistently indicate that exercise is neuroprotective and promotes recovery. Here, we assessed the effect of low and moderate intensity treadmill exercise on functional outcome and hippocampal neural proliferation after brain injury. Using the controlled cortical impact (CCI) mouse model of TBI, we show that 10 days of moderate intensity treadmill exercise initiated after CCI reduces anxiety-like behavior, improves hippocampus-dependent spatial memory, and promotes hippocampal proliferation and newborn neuronal survival. Pathophysiological measures including lesion volume and axon degeneration were not altered by exercise. Taken together, these data reveal that carefully titrated physical activity may be a safe and effective approach to promoting recovery after brain injury.
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“Evidence suggests that structured exercise can enhance sleep quality and cognitive function in pediatric and neurological populations (Liu et al. 2024; Zhang et al. 2024; Karelina et al. 2021; Herrera and Leon‐Rojas 2024), though its benefits following TBI remain unclear.”
From Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions (2026) · cites this paper as Karelina et al. 2021
In the citing paper
“Exercise has been shown to promote neuroplasticity, reduce fatigue, and support mood regulation in children with brain injuries (Karelina et al. 2021; Herrera and Leon‐Rojas 2024), which are essential components of sleep rehabilitation.”
From Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions (2026) · cites this paper as Karelina et al. 2021
In the citing paper
“Exercise has been shown to promote neuroplasticity, reduce fatigue, and support mood regulation in children with brain injuries (Karelina et al. 2021; Herrera and Leon‐Rojas 2024), which are essential components of sleep rehabilitation.”
From Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions (2026) · cites this paper as Karelina et al. 2021
In the citing paper
“Exercise has been shown to promote neuroplasticity, reduce fatigue, and support mood regulation in children with brain injuries (Karelina et al. 2021; Herrera and Leon‐Rojas 2024), which are essential components of sleep rehabilitation.”
From Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions (2026) · cites this paper as Karelina et al. 2021
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McCrory, P., Meeuwisse, W., Dvorak, J., Aubry, M., Bailes, J., Broglio, S., Cantu, R. C., Cassidy, D., Echemendia, R. J., Castellani, R. J., et al. (2017) · British Journal of Sports Medicine · doi:10.1136/bjsports-2017-097699 · Cited by 3,568
Inflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.008 · Cited by 1,440
Carroll, L., Cassidy, J. D., Peloso, P., Borg, J., von Holst, H., Holm, L., Paniak, C., & Pépin, M. (2004) · Journal of Rehabilitation Medicine · doi:10.1080/16501960410023859 · Cited by 1,326
Physical activity, exercise, depression and anxiety disorders
Ströhle, A. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-008-0092-x · Cited by 1,269
Neurogenesis and Exercise: Past and Future Directions
van Praag, H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8028-z · Cited by 645
Hall, E. D., Sullivan, P. G., Gibson, T. R., Pavel, K. M., Thompson, B. M., & Scheff, S. W. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.252 · Cited by 319 · cited 1×
“80,81 Further, areas of focal injury can alter more remote cell populations via secreted factors, spreading depolarizations and a variety of other mechanisms.”
Liu, Y., Chen, H., Wu, C., Kuo, Y., Yu, L., Huang, A., Wu, F., Chuang, J., & Jen, C. J. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.173088 · Cited by 199
Chen, M. J., & Russo‐Neustadt, A. A. (2009) · Hippocampus · doi:10.1002/hipo.20579 · Cited by 129
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Cited by
Lofitou, K., Kouki, E. P., Gavriel, C., Achilleos, H., Themistokleous, V., Bargiotas, P., Haarbauer‐Krupa, J., Paraskevopoulos, E., & Constantinidou, F. (2026) · Brain and Behavior · doi:10.1002/brb3.71556
Metadata
- Authors
- Karelina, K., Schneiderman, K., Shah, S., Fitzgerald, J., Cruz, R. V., Oliverio, R., Whitehead, B., Yang, J., & Weil, Z. M.
- Affiliations
- Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA.
- Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
- Nationwide Children's Hospital, Center for Injury Research and Policy, Columbus, Ohio, USA.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2021-06-10
- Volume
- 38
- Issue
- 13
- Pages
- 1858-1869
- ISSN
- 0897-7151
- 1557-9042
- Cited by
- 33
- References
- 9
- Language
- en
- Licence
- journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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- CoChat. (2026). Citation check: Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury. https://app.cochat.ai/papers/10.1089/neu.2020.7389
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- Karelina, K., Schneiderman, K., Shah, S., Fitzgerald, J., Cruz, R. V., Oliverio, R., Whitehead, B., Yang, J., & Weil, Z. M. (2021). Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury. Journal of Neurotrauma. https://doi.org/10.1089/neu.2020.7389
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