Traumatic Brain Injury (TBI) is widely recognized for its profound impact on brain function, but its consequences often extend beyond the brain to affect various extracranial systems. This narrative review explores the extracranial effects of TBI, focusing on the cardiovascular, respiratory, endocrine, and musculoskeletal systems, as well as immune response and metabolic changes. The review synthesizes current literature on how TBI-induced pathophysiological changes extend throughout the body and influence long-term outcomes, including physical and mental health. The interplay between intracranial injury and extracranial effects is critical for understanding the full scope of TBI’s impact. Future research should emphasize the development of comprehensive treatment protocols that address both intracranial and extracranial effects to improve outcomes for TBI patients.

Traumatic Brain Injury, extracranial effects, cardiovascular complications

Taylor, C.A.; Bell, J.M.; Breiding, M.J.; Xu, L. Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths-United States, 2007 and 2013. Morb. Mortal. Wkly. Rep. Surveill. Summ. 2017, 66, 1–16. [Google Scholar] [CrossRef] [PubMed]

Dewan, M.C.; Rattani, A.; Gupta, S.; Baticulon, R.E.; Hung, Y.C.; Punchak, M.; Agrawal, A.; Adeleye, A.O.; Shrime, M.G.; Rubiano, A.M.; et al. Estimating the global incidence of traumatic brain injury. J. Neurosurg. 2019, 130, 1080–1097. [Google Scholar] [CrossRef] [PubMed]

Finkelstein, E.; Corso, P.S.; Miller, T.R. The Incidence and Economic Burden of Injuries in the United States; Oxford University Press: Oxford, UK; New York, NY, USA, 2006; p. xiii. 187p. [Google Scholar]

Guo, S.; Han, R.; Chen, F.; Ji, P.; Liu, J.; Zhai, Y.; Chao, M.; Zhao, W.; Jiao, Y.; Fan, C.; et al. Epidemiological characteristics for patients with traumatic brain injury and the nomogram model for poor prognosis: An 18-year hospital-based study. Front. Neurol. 2023, 14, 1138217. [Google Scholar] [CrossRef]

McDonald, S.J.; Sun, M.; Agoston, D.V.; Shultz, S.R. The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome. J. Neuroinflamm. 2016, 13, 90. [Google Scholar] [CrossRef]

Xiong, C.; Hanafy, S.; Chan, V.; Hu, Z.J.; Sutton, M.; Escobar, M.; Colantonio, A.; Mollayeva, T. Comorbidity in adults with traumatic brain injury and all-cause mortality: A systematic review. BMJ Open 2019, 9, e029072. [Google Scholar] [CrossRef] [PubMed]

Burke, E.G.; Cansler, S.M.; Evanson, N.K. Indirect traumatic optic neuropathy: Modeling optic nerve injury in the context of closed head trauma. Neural Regen. Res. 2019, 14, 593–594. [Google Scholar]

Fuller, G.W.; Ransom, J.; Mandrekar, J.; Brown, A.W. Long-Term Survival Following Traumatic Brain Injury: A Population-Based Parametric Survival Analysis. Neuroepidemiology 2016, 47, 1–10. [Google Scholar] [CrossRef] [PubMed]

National Academies of Sciences, Engineering, and Medicine. Evaluation of the Disability Determination Process for Traumatic Brain Injury in Veterans; The National Academies Press: Washington, DC, USA, 2019. [Google Scholar] [CrossRef]

Rosner, M.J.; Newsome, H.H.; Becker, D.P. Mechanical brain injury: The sympathoadrenal response. J. Neurosurg. 1984, 61, 76–86. [Google Scholar] [CrossRef] [PubMed]

Jafari, A.A.; Shah, M.; Mirmoeeni, S.; Hassani, M.S.; Nazari, S.; Fielder, T.; Godoy, D.A.; Seifi, A. Paroxysmal sympathetic hyperactivity during traumatic brain injury. Clin. Neurol. Neurosurg. 2022, 212, 107081. [Google Scholar] [CrossRef] [PubMed]

Meyfroidt, G.; Baguley, I.J.; Menon, D.K. Paroxysmal sympathetic hyperactivity: The storm after acute brain injury. Lancet Neurol. 2017, 16, 721–729. [Google Scholar] [CrossRef]

Schroeppel, T.J.; Sharpe, J.P.; Magnotti, L.J.; Weinberg, J.A.; Clement, L.P.; Croce, M.A.; Fabian, T.C. Traumatic brain injury and β-blockers: Not all drugs are created equal. J. Trauma Acute Care Surg. 2014, 76, 504–509; discussion 509. [Google Scholar] [CrossRef] [PubMed]

El-Menyar, A.; Asim, M.; Khan, N.; Rizoli, S.; Mahmood, I.; Al-Ani, M.; Kanbar, A.; Alaieb, A.; Hakim, S.; Younis, B.; et al. Systemic and cerebro-cardiac biomarkers following traumatic brain injury: An interim analysis of randomized controlled clinical trial of early administration of beta blockers. Sci. Rep. 2024, 14, 19574. [Google Scholar] [CrossRef] [PubMed]

Kelly-Hedrick, M.; Liu, S.Y.; Temkin, N.; Barber, J.; Komisarow, J.; Manley, G.; Ohnuma, T.; Colton, K.; Treggiari, M.M.; Monson, E.E.; et al. Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study. Crit. Care Explor. 2023, 5, e0958. [Google Scholar] [CrossRef] [PubMed]

Nordness, M.F.; Maiga, A.W.; Wilson, L.D.; Koyama, T.; Rivera, E.L.; Rakhit, S.; de Riesthal, M.; Motuzas, C.L.; Cook, M.R.; Gupta, D.K.; et al. Effect of propranolol and clonidine after severe traumatic brain injury: A pilot randomized clinical trial. Crit. Care 2023, 27, 228. [Google Scholar] [CrossRef] [PubMed]

Li, L.M.; Vichayanrat, E.; Del Giovane, M.; Lai, H.H.L.; Iodice, V. Autonomic dysfunction after moderate-to-severe traumatic brain injury: Symptom spectrum and clinical testing outcomes. BMJ Neurol. Open 2022, 4, e000308. [Google Scholar] [CrossRef]

Wesolowski, E.; Ahmed, Z.; Di Pietro, V. History of concussion and lowered heart rate variability at rest beyond symptom recovery: A systematic review and meta-analysis. Front. Neurol. 2023, 14, 1285937. [Google Scholar] [CrossRef] [PubMed]

Khalid, F.; Yang, G.L.; McGuire, J.L.; Robson, M.J.; Foreman, B.; Ngwenya, L.B.; Lorenz, J.N. Autonomic dysfunction following traumatic brain injury: Translational insights. Neurosurg. Focus 2019, 47, E8. [Google Scholar] [CrossRef] [PubMed]

Bao, W.; Lin, Y.; Chen, Z. The Peripheral Immune System and Traumatic Brain Injury: Insight into the role of T-helper cells. Int. J. Med. Sci. 2021, 18, 3644–3651. [Google Scholar] [CrossRef] [PubMed]