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Goutnik, M.;  Goeckeritz, J.;  Sabetta, Z.;  Curry, T.;  Willman, M.;  Willman, J.;  Thomas, T.C.;  Lucke-Wold, B. Helmet Design and Neurotrauma Prevention. Encyclopedia. Available online: https://encyclopedia.pub/entry/28068 (accessed on 18 July 2025).
Goutnik M,  Goeckeritz J,  Sabetta Z,  Curry T,  Willman M,  Willman J, et al. Helmet Design and Neurotrauma Prevention. Encyclopedia. Available at: https://encyclopedia.pub/entry/28068. Accessed July 18, 2025.
Goutnik, Michael, Joel Goeckeritz, Zackary Sabetta, Tala Curry, Matthew Willman, Jonathan Willman, Theresa Currier Thomas, Brandon Lucke-Wold. "Helmet Design and Neurotrauma Prevention" Encyclopedia, https://encyclopedia.pub/entry/28068 (accessed July 18, 2025).
Goutnik, M.,  Goeckeritz, J.,  Sabetta, Z.,  Curry, T.,  Willman, M.,  Willman, J.,  Thomas, T.C., & Lucke-Wold, B. (2022, September 29). Helmet Design and Neurotrauma Prevention. In Encyclopedia. https://encyclopedia.pub/entry/28068
Goutnik, Michael, et al. "Helmet Design and Neurotrauma Prevention." Encyclopedia. Web. 29 September, 2022.
Helmet Design and Neurotrauma Prevention
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This entry is adapted from the peer-reviewed paper 10.3390/biomechanics2040039

Neurotrauma is an important, often preventable cause of morbidity and mortality. Between 180 and 250 traumatic brain injuries (TBIs) occur per 100,000 population per year in the U.S.. Helmets have been employed by humans for thousands of years and have served as a crucial instrument by which we protect ourselves from and minimize the effects of traumatic brain injury. Substantial evidence from systematic reviews and meta-analyses points toward the protective effectiveness (often >60%) of helmets in preventing TBIs in athletes, cyclists and motorcyclists. However, when stratifying TBI by severity, helmets may be less effective or even ineffective in preventing milder forms of TBI such as concussion. Helmet design has been predicated on linear acceleration as a metric corresponding to head injury. This has served well in preventing catastrophic injuries. However, rotational acceleration is more likely implicated in the pathophysiology of milder brain injuries, including concussion.

helmet military sport secondary injury

1. Current Sports Helmet Design

The mandated use of helmets in organized sports dates back as early as the 1940’s when the National Collegiate Athletic Association (NCAA) and National Football League (NFL) made helmets a requirement for players to reduce head-related injuries [1]. Since this time, multiple organizations have developed standards for testing and producing sports helmets. While the implementation of sports helmets has successfully reduced catastrophic head-related injuries, including traumatic brain injuries (TBI) and orofacial injuries, the risk of concussive injuries remains unmitigated. This discrepancy in selective protection may be explained by how helmets are tested and certified, with the current standard for testing helmets focusing on the use of linear acceleration, which has demonstrated a reduction of TBI and skull fractures, but not concussive injury [2]. Research has demonstrated that the primary mechanism of injury leading to concussions in sports is the result of rotational acceleration, which is not explicitly tested for by certifying organizations [3][4].
Current sports helmets are designed to protect against punches, falls, projectiles, collisions, and abrasion, and can be grossly organized into two main categories—single-impact and multi-impact helmets [5]. However, virtually all current sports helmets have the basic design of an inner comfort liner, an impact energy attenuating liner, a restraint system, and an outer shell [6]. Single-impact helmets are designed to withstand high-impact encounters only once. Examples of these include bicycle, mountaineering, and equestrian helmets. The energy attenuating liner in these helmets is typically constructed of lightweight expanded polystyrene (EPS) foam, which does well in dissipating energy, but permanently deforms after impact [1]. On the other hand, multi-impact helmets are designed to withstand multiple impacts and are used in US football, hockey, motorcross, and rugby. The resilience to multiple impacts is accomplished by construction with either vinyl nitrile (VN) or expanded polypropylene (EPP) foam for the energy attenuating liner. VN and EPP can return to their original form after impact; however, VN performs better with lower energy impacts than EPP, which performs better at higher energy impacts [1][7]. In both helmets, the outer shell functions to distribute the force of impact along the area of the energy attenuating liner. Shells are commonly constructed of polycarbonate (PC) or ABS plastic, but some helmets may have hard shells composed of composites, such as fiberglass or carbon fiber [8][9].
Further variations in helmet design exist according to the dangers encountered in each sport, as well as practicality, ease of use, and aesthetics. Sports (e.g., lacrosse, hockey, and baseball) where the impact from a projectile is of concern may implement a face guard (typically either a wired frame or an extension of the helmet’s shell) to protect against orofacial injuries [10][11]. Cycling and mountaineering helmets are often engineered to be highly aerodynamic and as light as possible to avoid hindering the user’s performance [12]. Helmets used in motorcycle-variant sports are designed with thicker protective layers that aerodynamically encapsulate the entire head to protect against greater risks associated with high speed [13].

2. Current Military Helmet Design

The current issue US military helmet for combat use is the advanced combat helmet (ACH), and previously was the personnel armor system for ground troops (PASGT) in the late 1990’ and early 2000s [14]. Prior work has highlighted the blunt impact standard limitation to linear head acceleration [15], with the need to focus on rotational head motion, the likely mechanism contributing to diffuse axonal injury (DAI) [15][16][17][18]. Military specification (mil-spec) requires a blunt impact acceleration limit testing for pass/fail criteria of the ACH, but does not require rotational component testing [17]. Blast-induced TBI (BTBI) is also a mechanism of combat-induced diffuse axonal injury where blast waves cause rotational forces on the brain to induce DAI.
The ACH is equipped with high-strength Kevlar 129 fibers, housed in a 7.8 mm thick composite shell [19][20]. Previous literature has highlighted the efficacy of the ACH head protection in reduced likelihood of blast-induced mild TBI (mTBI), where levels of protection increase with peak blast exposure [17], as well as protection against blast-induced intracranial pressure (ICP) increases and brain strains [21][22]. Although there is increased overall protection against blast exposures, helmet design still has limitations. For example, Zhang et al. [21] demonstrated that blast waves could directly penetrate through the gap between the forehead and the helmet, causing further deformation of padding.
Warfighters who engage in parachute combat rather than ground combat are twice as likely to sustain any form of TBI [23] and are three times more likely to sustain a mild form of a TBI wearing the PASGT combat helmet compared to the ACH [23]. This is likely due to the higher velocity impacts sustained in parachute jumping and a suspension system that is not as advanced as the ACH. The current ACH uses a suspension padding system that offers protection against axonal shearing, but the preclinical models are still limited regarding how effective these padding systems are in humans [16].
Thus, slight modifications to the ACH and/or future helmet design mil-spec testing may reduce the incidence of DAI and the prevalence of military-related TBI for warfighters. Preclinical animal models may provide further adequate preliminary evidence of the need to address diffuse rotational injury associated with warfighters.

3. Current Construction Helmet Design

In the United States, the construction industry is responsible for the largest portion of industrial injuries and induces an estimated healthcare and economic burden of $11.5 billion in direct medical costs and lost wages, as last investigated in 2002 [24]. The United States Bureau of Labor Statistics reports that falls in the construction industry account for 62.9% of all fatal falls [25]. Industrial workers 65 years of age and older are at the greatest risk for more severe outcomes after TBI, including death. In addition, this age group has a higher incidence of falls, and within the construction industry, these workers have the highest (57%) frequency of fall-related injuries, including TBIs. This increased risk for injury demonstrates the importance of proper personal protective equipment (PPE), such as helmets. PPE is defined as a control measure used in hazardous situations where the hazard cannot be eliminated or controlled to an acceptable level through engineering design or administrative actions [26]. According to Occupational Safety and Health Administration (OSHA) and the United States Army Corps of Engineers (USACE) regulations, all employees and visitors to a construction site must wear a provided hard hat [26]. These industrial safety helmets are required in conditions where objects might fall from above and strike workers on the head, workers may bump their heads against objects, or there is possible contact with electrical hazards. The American National Standards Institute (ANSI) regulates hard hats by setting performance and requirement testing standards. Type I and II helmets reduce force to the top of the head, while type III classified helmets can reduce impact to the top and sides of the head. Industrial safety helmets have a suspension design that is intended to reduce the force of impact and penetrations of small objects. Furthermore, a study was performed to assess their effectiveness against larger objects and found these helmets were capable of reducing the force and linear acceleration for vertical impact [25][26][27]. They also reduced the likelihood of skull fracture and severe injury, further supporting the importance of industrial safety helmets.
Construction-related injuries to the head can result in skull fractures and localized underlying brain injury, closed head injuries, neck injuries, and rotational injuries leading to diffuse axonal injury [28]. A study was performed to assess the impact of hard hats during varied neck movements utilizing surface electromyography sensors on the upper trapezius muscles of volunteer subjects [29]. The researchers demonstrated that muscle activity and fatigue were not increased while wearing an industrial hard hat, suggesting that this protective equipment is not causing further detriment to workers’ neck strain [29]. Vertical impact occurs in 36% of falling object cases, yet most injuries include a rotational injury [28]. Though industrial safety helmets are required PPE in the construction industry, these helmets have suspension designs that primarily protect against vertical impact. This design may be beneficial for many types of possible injury at a construction site, but it does not protect the wearer during a fall or when faced with a rotational injury (Figure 1).
Biomechanics 02 00039 g001 550
Figure 1. Industrial safety helmets have a suspension design that prevents injury from vertical impact. These helmets are not designed to prevent injury from side or rotational impacts that would increase injury severity and diffuse axonal injury.
Finite element analysis is a numerical analysis technique utilized to assess the engineering and design of helmets by mathematically modeling physical contributions such as force. This mathematical modeling utilizes a scoring system such as the head injury criteria (HIC) score, incorporating acceleration and time, where a score of 1000 is considered a safe limit [30]. This widely used score has been utilized to improve and test different helmet materials such as Carbon Fiber and Polyethylene [31]. In addition, finite element analysis can be utilized to assess diffuse axonal injury computationally via von Mises stress [27]. A study evaluating simulation-based impact on construction helmets indicated that a 2 kg cylinder vertical impact has a 50% chance of causing mild diffuse axonal injury, which increases in severity as impact speed increases. However, it was limited by the lack of modeling any elements of rotational acceleration [27]. This testing provides classifications for helmets for one-time impact, yet industrial helmets regularly endure multiple impacts. One study evaluated the damage and vulnerability induced by repeated impacts on the helmets’ shock absorption performance [32]. An endurance limit was determined for the helmet, where cumulative damage from multiple impacts degraded the shock absorption performance when the impacts were greater than the endurance limit. For example, a type I industrial helmet’s endurance limit was found to be a drop height of 1.22 m [32].
The largest challenge with construction-related safety is workers wearing the industrial safety helmet. Industrial safety helmets have been accused of being too heavy and uncomfortable to wear while working; thus, many workers often choose not to wear helmets when possible. One initiative for promoting wearing helmets on construction sites has been artificial intelligence technology for safety helmet recognition [33]. While improvements in industrial helmet design are needed for comfort and protection against rotational injury, the use of these safety helmets is still effective in protecting the wearer from injury. An analysis of work-related injuries demonstrated that safety helmets meeting current OSHA and ANSI requirements more effectively prevented intracranial injury in comparison to no helmet at all [34].
While helmets can effectively dissipate and reduce impact and acceleration-deceleration forces, they do not entirely prevent energy transfer and the risk of concussion. The pathophysiological consequences of single or repeated concussions while wearing a helmet are needed but present challenges when adapting experiments to translational TBI models. Helmets are designed for human heads and impact based on bipedal kinematics, where common TBI animal models introduce varied head and brain shapes and quadrupedal movement that can change the fundamental dynamics of applied forces, where the temporal and spatial profile of physiological alterations, diffuse axonal injury, and secondary injury sequelae can be influenced.
In conclusion, industrial safety helmets are beneficial for preventing head injury, but there is a large gap in work-related injury research. Mechanistic understanding and appropriate injury models, including rotational acceleration, are required to develop more protective helmets for work-related traumatic brain injuries.

4. Secondary Injury Prevention

While there are likely a plethora of factors that influence TBI, linear and rotational acceleration are two of the most significant. Linear acceleration is believed to produce focal trauma at both coup and contrecoup locations within the brain [35]. Examples of focal injuries include epidural hematomas, skull fractures, and cerebral contusions [35][36]. Conversely, rotational acceleration produces more diffuse trauma within the brain through shearing forces [35][37]. For years, reducing linear acceleration has been one of the primary goals of helmet design. However, it was not until 2018 that the National Operating Committee for Standards in Athletic Equipment updated the criteria to include rotational acceleration in the design of new helmets [38]. In a 2020 evaluation of combat helmets released by the US Army Combat Capabilities Development Command, they demonstrated that while, on average, the Army Advanced Combat Helmet (ACH) produced a statistically significant reduction in linear acceleration compared to no helmet. However, it failed to produce a statistically significant average reduction in rotational acceleration and even increased rotational acceleration at higher force impacts [39]. Consequently, helmet designs in sports and combat have historically neglected to consider rotational acceleration and the resultant more mild traumatic brain injuries (mTBI) such as concussion and subconcusion [8][40].
Rotational acceleration produces axonal shearing, obstructing axonal function, and causing an accumulation of amyloid-beta precursor protein that peaks after 24–48 h [41][42][43]. In addition, shearing and mechanical forces produce plasma membrane instability resulting in potassium leakage and neuronal depolarization [44][45]. As a result, the excitatory neurotransmitter glutamate is released and binds NMDA receptors, generating a cycle of potentially neurotoxic hyperexcitation [43][46][47][48]. This drastically elevates intercellular calcium and sodium concentrations and destabilizes mitochondrial function as a vital calcium buffer system within the cell [49][50][51]. As a result, calcium-dependent proteases and lipases are activated and reactive oxygen species production increases, causing oxidative stress within the cell [52][53]. Elevated oxidative stress within the cell is believed to promote perturbation within the endoplasmic reticulum (ER) and a subsequent accumulation of unfolded proteins. The unfolded protein response (UPR) initially functions to resolve ER stress through inhibition of protein synthesis and proteolysis of misfolded or unfolded proteins [54][55]. With a failure of ER stress resolution over time, the ER UPR pathway ultimately upregulates caspases and pro-apoptotic pathways, promoting cell death [54][56][57][58]. These functions can be exacerbated with repeated injury, and may be targeted for helmet innovation.

References

  1. Cantu, R.C. Neurologic Athletic Head and Spine Injuries; W.B. Saunders: Philadelphia, PA, USA, 2000.
  2. Post, A.; Hoshizaki, T.B. Mechanisms of brain impact injuries and their prediction: A review. Trauma 2012, 14, 327–349.
  3. Bain, A.C.; Meaney, D.F. Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury. J. Biomech. Eng. 2000, 122, 615–622.
  4. Rueda, M.A.F.; Cui, L.; Gilchrist, M.D. Finite element modelling of equestrian helmet impacts exposes the need to address rotational kinematics in future helmet designs. Comput. Methods Biomech. Biomed. Eng. 2011, 14, 1021–1031.
  5. Hoshizaki, T.; Brien, S. The Science and Design of Head Protection in Sport. Neurosurgery 2004, 55, 956–966.
  6. McIntosh, A.S.; Andersen, T.E.; Bahr, R.; Greenwald, R.; Kleiven, S.; Turner, M.; Varese, M.; McCrory, P. Sports helmets now and in the future. Br. J. Sports Med. 2011, 45, 1258–1265.
  7. Post, A.; Hoshizaki, T.B.; Brien, S. Head Injuries, Measurement Criteria and Helmet Design. In Routledge Handbook of Ergonomics in Sport and Exercise; Hong, Y., Ed.; Routledge Publishers: London, UK, 2012.
  8. Hoshizaki, T.B.; Post, A.; Oeur, R.A.; Brien, S.E. Current and Future Concepts in Helmet and Sports Injury Prevention. Neurosurgery 2014, 75, S136–S148.
  9. Bustamante, M.C.; Bruneau, D.; Barker, J.B.; Gierczycka, D.; Coralles, M.A.; Cronin, D.S. Component-Level Finite Element Model and Validation for a Modern American Football Helmet. J. Dyn. Behav. Mater. 2019, 5, 117–131.
  10. Tuna, E.B.; Ozel, E. Factors Affecting Sports-Related Orofacial Injuries and the Importance of Mouthguards. Sports Med. 2014, 44, 777–783.
  11. Ranalli, D.N.; Demas, P.N. Orofacial Injuries from Sport. Sports Med. 2002, 32, 409–418.
  12. Underwood, L.; Jermy, M.; Eloi, P.; Cornillon, G. Helmet position, ventilation holes and drag in cycling. Sports Eng. 2015, 18, 241–248.
  13. Gibson, T.J.; Thai, K. Helmet Protection against Basilar Skull Fracture; Australian Transport Safety Bureau: Canberra, Australian, 2007.
  14. Scharine, A.A.; Binseel, M.S.; Mermagen, T.; Letowski, T.R. Sound localisation ability of soldiers wearing infantry ACH and PASGT helmets. Ergonomics 2014, 57, 1222–1243.
  15. York, S.; Edwards, E.D.; Jesunathadas, M.; Landry, T.; Piland, S.G.; Plaisted, T.A.; Kleinberger, M.; Gould, T.E. Influence of Friction at the Head-Helmet Interface on Advanced Combat Helmet (ACH) Blunt Impact Kinematic Performance. Mil. Med. 2022, usab547.
  16. Bradfield, C.; Vavalle, N.; DeVincentis, B.; Wong, E.; Luong, Q.; Voo, L.; Carneal, C. Combat Helmet Suspension System Stiffness Influences Linear Head Acceleration and White Matter Tissue Strains: Implications for Future Helmet Design. Mil. Med. 2018, 183, 276–286.
  17. Terpsma, R.; Carlsen, R.W.; Szalkowski, R.; Malave, S.; Fawzi, A.L.; Franck, C.; Hovey, C. Head Impact Modeling to Support a Rotational Combat Helmet Drop Test. Mil. Med. 2021, usab374.
  18. Begonia, M.; Humm, J.; Shah, A.; Pintar, F.A.; Yoganandan, N. Influence of ATD versus PMHS reference sensor inputs on computational brain response in frontal impacts to advanced combat helmet (ACH). Traffic Inj. Prev. 2018, 19, S159–S161.
  19. Sone, J.Y.; Kondziolka, D.; Huang, J.H.; Samadani, U. Helmet efficacy against concussion and traumatic brain injury: A review. J. Neurosurg. 2017, 126, 768–781.
  20. Grujicic, M.; Bell, W.C.; Pandurangan, B.; Glomski, P.S. Fluid/Structure Interaction Computational Investigation of Blast-Wave Mitigation Efficacy of the Advanced Combat Helmet. J. Mater. Eng. Perform. 2011, 20, 877–893.
  21. Zhang, L.; Makwana, R.; Sharma, S. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet. Front. Neurol. 2013, 4, 88.
  22. Nyein, M.K.; Jason, A.M.; Yu, L.; Pita, C.M.; Joannopoulos, J.D.; Moore, D.F.; Radovitzky, R.A. In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury. Proc. Natl. Acad. Sci. USA 2010, 107, 20703–20708.
  23. Ivins, B.J.; Crowley, J.S.; Johnson, J.; Warden, D.L.; Schwab, K.A. Traumatic brain injury risk while parachuting: Comparison of the personnel armor system for ground troops helmet and the advanced combat helmet. Mil. Med. 2008, 173, 1168–1172.
  24. Waehrer, G.M.; Dong, X.S.; Millera, T.; Haile, E.; Men, Y. Costs of occupational injuries in construction in the United States. Accid. Anal. Prev. 2007, 39, 1258–1266.
  25. U.S. Bureau of Labor Statistics. Available online: https://www.bls.gov/ (accessed on 24 July 2022).
  26. 1926.100—Head Protection. Occupational Safety and Health Administration. Available online: https://www.osha.gov/laws-regs/regulations/standardnumber/1926/1926.100 (accessed on 24 July 2022).
  27. Long, J.; Yang, J.; Lei, Z.; Liang, D. Simulation-based assessment for construction helmets. Comput. Methods Biomech. Biomed. Eng. 2015, 18, 24–37.
  28. Hume, A.; Mills, N.J.; Gilchrist, A. Industrial Head Injuries and the Performance of the Helmets. 1995. Available online: https://www.semanticscholar.org/paper/Industrial-head-injuries-and-the-performance-of-Hulme-Mills/03bf8f6afc4729f9529ce630daed14473b11ecb8 (accessed on 24 July 2022).
  29. Magnuson, S.; Autenrieth, D.A.A.; Stack, T.; Risser, S.; Gilkey, D. Are hard hats a risk factor for WRMSD in the cervical-thoracic region? Work Read. Mass. 2020, 66, 437–443.
  30. Wu, J.Z.; Pan, C.S.; Wimer, B.M.; Rosen, C.L. Finite element simulations of the head-brain responses to the top impacts of a construction helmet: Effects of the neck and body mass. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 2017, 231, 58–68.
  31. Naresh, P.; Krishnudu, D.M.; Babu, A.H.; Hussain, P. Design And Analysis of Industrial Helmet. Int. J. Mech. Eng. Res. 2015, 5, 81–95.
  32. Wu, J.Z.; Pan, C.S.; Wimer, B.M. Evaluation of the shock absorption performance of construction helmets under repeated top impacts | Elsevier Enhanced Reader. Eng. Fail. Anal. 2019, 96, 330–339.
  33. Wei, L.; Cheng, M.; Feng, M.; Lijuan, Z. Research on Recognition of Safety Helmet Wearing of Electric Power Construction Personnel Based on Artificial Intelligence Technology. IOP Sci. 2020, 1684, 012013.
  34. Kim, S.C.; Ro, Y.S.; Shin, S.D.; Kim, J.Y. Preventive Effects of Safety Helmets on Traumatic Brain Injury after Work-Related Falls. Int. J. Environ. Res. Public Health 2016, 13, 1063.
  35. Tierney, G. Concussion biomechanics, head acceleration exposure and brain injury criteria in sport: A review. Sports Biomech. 2021, 1–29.
  36. Kleiven, S. Why Most Traumatic Brain Injuries are Not Caused by Linear Acceleration but Skull Fractures are. Front. Bioeng. Biotechnol. 2013, 1, 15.
  37. Rowson, S.; Bland, M.L.; Campolettano, E.T.; Press, J.N.; Rowson, B.; Smith, J.A.; Sproule, D.W.; Tyson, A.M.; Duma, S.M. Biomechanical Perspectives on Concussion in Sport. Sports Med. Arthrosc. Rev. 2016, 24, 100–107.
  38. Trotta, A.; Annaidh, A.N.; Burek, R.O.; Pelgrims, B.; Ivens, J. Evaluation of the head-helmet sliding properties in an impact test. J. Biomech. 2018, 75, 28–34.
  39. Neice, R.; Plaisted, T. Evaluation of a Combat Helmet Under Combined Translational and Rotational Impact Loading. 2020. Available online: https://apps.dtic.mil/sti/citations/AD1120852 (accessed on 24 July 2022).
  40. McKeithan, L.; Hibshman, N.; Yengo-Kahn, A.M.; Solomon, G.S.; Zuckerman, S.L. Sport-Related Concussion: Evaluation, Treatment, and Future Directions. Med. Sci. 2019, 7, 44.
  41. Jamjoom, A.A.B.; Rhodes, J.; Andrews, P.J.D.; Grant, S.G.N. The synapse in traumatic brain injury. Brain 2020, 144, 18–31.
  42. Pavlovic, D.; Pekic, S.; Stojanovic, M.; Popovic, V. Traumatic brain injury: Neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary 2019, 22, 270–282.
  43. Romeu-Mejia, R.; Giza, C.C.; Goldman, J.T. Concussion Pathophysiology and Injury Biomechanics. Curr. Rev. Musculoskelet. Med. 2019, 12, 105–116.
  44. Keating, C.E.; Cullen, D.K. Mechanosensation in traumatic brain injury. Neurobiol. Dis. 2021, 148, 105210.
  45. Wofford, K.L.; Grovola, M.R.; Adewole, D.O.; Browne, K.D.; Putt, M.E.; O’Donnell, J.C.; Cullen, D.K. Relationships between injury kinematics, neurological recovery, and pathology following concussion. Brain Commun. 2021, 3, fcab268.
  46. Tehse, J.; Taghibiglou, C. The overlooked aspect of excitotoxicity: Glutamate-independent excitotoxicity in traumatic brain injuries. Eur. J. Neurosci. 2019, 49, 1157–1170.
  47. Guerriero, R.M.; Giza, C.C.; Rotenberg, A. Glutamate and GABA Imbalance Following Traumatic Brain Injury. Curr. Neurol. Neurosci. Rep. 2015, 15, 27.
  48. Wofford, K.L.; Loane, D.J.; Cullen, D.K. Acute drivers of neuroinflammation in traumatic brain injury. Neural Regen. Res. 2019, 14, 1481–1489.
  49. Hubbard, W.B.; Joseph, B.; Spry, M.; Vekaria, H.J.; Saatman, K.E.; Sullivan, P.G. Acute Mitochondrial Impairment Underlies Prolonged Cellular Dysfunction after Repeated Mild Traumatic Brain Injuries. J. Neurotrauma 2019, 36, 1252–1263.
  50. Cheng, G.; Kong, R.-H.; Zhang, L.-M.; Zhang, J.-N. Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies. Br. J. Pharmacol. 2012, 167, 699–719.
  51. Verweij, B.H.; Muizelaar, J.P.; Vinas, F.C.; Peterson, P.L.; Xiong, Y.; Lee, C.P. Impaired cerebral mitochondrial function after traumatic brain injury in humans. J. Neurosurg. 2000, 93, 815–820.
  52. Ismail, H.; Shakkour, Z.; Tabet, M.; Abdelhady, S.; Kobaisi, A.; Abedi, R.; Nasrallah, L.; Pintus, G.; Al-Dhaheri, Y.; Mondello, S.; et al. Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone. Antioxidants 2020, 9, 943.
  53. Sahel, D.K.; Kaira, M.; Raj, K.; Sharma, S.; Singh, S. Mitochondrial dysfunctioning and neuroinflammation: Recent highlights on the possible mechanisms involved in Traumatic Brain Injury. Neurosci. Lett. 2019, 710, 134347.
  54. Brady, R.D.; Bird, S.; Sun, M.; Yamakawa, G.R.; Major, B.P.; Mychasiuk, R.; O’Brien, T.J.; McDonald, S.J.; Shultz, S.R. Activation of the Protein Kinase R–Like Endoplasmic Reticulum Kinase (PERK) Pathway of the Unfolded Protein Response after Experimental Traumatic Brain Injury and Treatment with a PERK Inhibitor. Neurotrauma Rep. 2021, 2, 330–342.
  55. Scheper, W.; Hoozemans, J.J.M. The unfolded protein response in neurodegenerative diseases: A neuropathological perspective. Acta Neuropathol. 2015, 130, 315–331.
  56. Krishnamurthy, K.; Laskowitz, D.T. Cellular and Molecular Mechanisms of Secondary Neuronal Injury. In Translational Research in Traumatic Brain Injury; Laskowitz, D., Grant, G., Eds.; CRC Press, Taylor and Francis Group: Boca Raton, FL, USA, 2016.
  57. Hetz, C.; Axten, J.M.; Patterson, J.B. Pharmacological targeting of the unfolded protein response for disease intervention. Nat. Chem. Biol. 2019, 15, 764–775.
  58. Kim, I.; Xu, W.; Reed, J.C. Cell death and endoplasmic reticulum stress: Disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 2008, 7, 1013–1030.
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Michael Goutnik
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