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Current Reviews in Musculoskeletal Medicine
Published in: Current Reviews in Musculoskeletal Medicine 2/2019

01-06-2019 | Central Nervous System Trauma | Concussion (C Senter and M Kapadia, Section Editors)

Concussion Pathophysiology and Injury Biomechanics

Authors: Rafael Romeu-Mejia, Christopher C. Giza, Joshua T. Goldman

Published in: Current Reviews in Musculoskeletal Medicine | Issue 2/2019

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Abstract

Purpose of Review

The concussion public health burden has increased alongside our knowledge of the pathophysiology of mild traumatic brain injury (mTBI). The purpose of this review is to summarize our current understanding of mTBI pathophysiology and biomechanics and how these underlying principles correlate with clinical manifestations of mTBI.

Recent Findings

Changes in post-mTBI glutamate and GABA concentrations seem to be region-specific and time-dependent. Genetic variability may predict recovery and symptom severity while gender differences appear to be associated with the neuroinflammatory response and neuroplasticity. Ongoing biomechanical research has shown a growing body of evidence in support of an “individual-specific threshold” for mTBI that varies based on individual intrinsic factors.

Summary

The literature demonstrates a well-characterized timeframe for mTBI pathophysiologic changes in animal models while work in this area continues to grow in humans. Current human research shows that these underlying post-mTBI effects are multifactorial and may correlate with symptomatology and recovery. While wearable sensor technology has advanced biomechanical impact research, a definitive concussion threshold remains elusive.
Literature
1.
2.
DeMatteo CA, Hanna SE, Mahoney WJ, Hollenberg RD, Scott LA, Law MC, et al. My child doesn’t have a brain injury, he only has a concussion. Pediatrics. 2010;125:327–34.CrossRefPubMed
3.
McCrory P, Meeuwisse W, Dvořák J, Aubry M, Bailes J, Broglio S, et al. Consensus statement on concussion in sport—the 5th international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med. 2017;51:838–47.PubMed
4.
5.
Lumba-Brown A, Yeates KO, Sarmiento K, Breiding MJ, Haegerich TM, Gioia GA, et al. Centers for disease control and prevention guideline on the diagnosis and management of mild traumatic brain injury among children. JAMA Pediatr. 2018;172:e182853.CrossRefPubMed
6.
Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury–related emergency department visits, hospitalizations, and deaths — United States, 2007 and 2013. MMWR Surveill Summ. 2017;66:1–16.CrossRefPubMedPubMedCentral
7.
Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Centers Dis Control Prev Natl Cent Inj Prev Control 2010;891–904.
8.
Coronado VG, Haileyesus T, Cheng TA, Bell JM, Haarbauer-Krupa J, Lionbarger MR, et al. Trends in sports-and recreation-related traumatic brain injuries treated in US emergency departments: the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) 2001-2012. J Head Trauma Rehabil. 2015;30:185–97.CrossRefPubMedPubMedCentral
9.
Covassin T, Moran R, Elbin RJ. Sex differences in reported concussion injury rates and time loss from participation: an update of the national collegiate athletic association injury surveillance program from 2004-2005 through 2008-2009. J Athl Train. 2016;51:189–94.CrossRefPubMedPubMedCentral
10.
Giza CC, Kutcher JS, Ashwal S, Barth J, Getchius TSD, Gioia GA, et al. Summary of evidence-based guideline update: evaluation and management of concussion in sports: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80:2250–7.CrossRefPubMedPubMedCentral
11.
Herring SA, Cantu RC, Guskiewicz KM, Putukian M, Kibler WB. Concussion (mild traumatic brain injury) and the team physician. Med Sci Sports Exerc. 2011;43:2412–22.CrossRefPubMed
12.
13.
Steenerson K, Starling AJ. Pathophysiology of sports-related concussion. Neurol Clin Elsevier Inc. 2017;35:403–8.CrossRef
14.
Cantu D, Walker K, Andresen L, Taylor-Weiner A, Hampton D, Tesco G, et al. Traumatic brain injury increases cortical glutamate network activity by compromising GABAergic control. Cereb Cortex. 2015;25:2306–20.CrossRefPubMed
15.
16.
Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990;73:889–900.CrossRefPubMed
17.
Mc Fie S, Abrahams S, Patricios J, Suter J, Posthumus M, September AV. Inflammatory and apoptotic signalling pathways and concussion severity: a genetic association study. J Sports Sci Routledge. 2018;36:2226–34.CrossRef
18.
19.
Yi JH, Hazell AS. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int. 2006;48:394–403.CrossRefPubMed
20.
•• Yasen AL, Smith J, Christie AD. Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study Alia L. Yasen. J Neurophysiol. 2018;120:1318–22 One of the first studies to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mTBI in humans. Showed differences in glutamate and GABA concentration in the brain post-mTBI did not follow the pattern typically seen in the animal literature and concluded they may be region-specific and time-dependent. CrossRefPubMed
21.
Cheng G, Kong RH, Zhang LM, Zhang JN. Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies. Br J Pharmacol. 2012;167:699–719.CrossRefPubMedPubMedCentral
22.
Barkhoudarian G, Hovda DA, Giza CC. The molecular pathophysiology of concussive brain injury. Clin Sports Med Elsevier Inc. 2011;30:33–48.CrossRef
23.
Monaghan KG, Jackson CE, KuKuruga DL, Feldman GL. Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine. Am J Med Genet. 2000;94:120–4.CrossRefPubMed
24.
• McDevitt J. CNS voltage-gated calcium channel gene variation and prolonged recovery following sport-related concussion. Orthop J Sport Med. 2016;4:2325967116S0007 Showed that polymorphism of the CACNAE1 gene in humans can affect recovery time and symptom duration after concussive injuries. Provides evidence of genetic influence and variability of post-concussive injury recovery. CrossRef
25.
Gurkoff GG, Shahlaie K, Lyeth BG, Berman RF. Voltage-gated calcium channel blockers for the treatment of traumatic brain injury. New Ther Trauma Brain Inj. Elsevier; 2017.
26.
Mihalik JP, Stump JE, Collins MW, Lovell MR, Field M, Maroon JC. Posttraumatic migraine characteristics in athletes following sports-related concussion. J Neurosurg. 2005;102:850–5.CrossRefPubMed
27.
Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res. 1991;561:106–19.CrossRefPubMed
28.
Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Lactate accumulation following concussive brain injury: the role of ionic fluxes induced by excitatory amino acids. Brain Res. 1995;674:196–204.CrossRefPubMed
29.
Kalimo H, Rehncrona S, Söderfeldt B, Olsson Y, Siesjö BK. Brain lactic acidosis and ischemic cell damage: 2. Histopathol J Cereb Blood Flow Metab. 1981;1:313–27.CrossRef
30.
Peskind ER, Petrie EC, Cross DJ, Pagulayan K, McCraw K, Hoff D, et al. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms. Neuroimage. Elsevier B.V.; 2011;54:S76–82.
31.
Byrnes KR, Wilson CM, Brabazon F, Von Leden R, Jurgens JS, Oakes TR, et al. FDG-PET imaging in mild traumatic brain injury: a critical review. Front Neuroenerg. 2014;6:13.
32.
Vagnozzi R, Signoretti S, Cristofori L, Alessandrini F, Floris R, Isgró E, et al. Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain. 2010;133:3232–42.CrossRefPubMed
33.
34.
DeFord SM, Wilson MS, Rice AC, Clausen T, Rice LK, Barabnova A, et al. Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice. J Neurotrauma. 2002;19:427–38.CrossRefPubMed
35.
Prins ML, Hovda DA. The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats. J Neurotrauma. 2009;26:1083–93.CrossRefPubMedPubMedCentral
36.
Appelberg KS, Hovda DA, Prins ML. The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat. J Neurotrauma. 2009;26:497–506.CrossRefPubMedPubMedCentral
37.
Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, et al. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med. 2014;40:412–21.CrossRefPubMed
38.
Martin NA, Patwardhan RV, Alexander MJ, Africk CZ, Lee JH, Shalmon E, et al. Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. J Neurosurg. 1997;87:9–19.CrossRefPubMed
39.
Choe MC, Babikian T, Difiori J, Hovda DA, Giza CC. A pediatric perspective on concussion pathophysiology. Curr Opin Pediatr. 2012;24:689–95.CrossRefPubMed
40.
Clausen M, Pendergast DR, Willer B, Leddy J. Cerebral blood flow during treadmill exercise is a marker of physiological postconcussion syndrome in female athletes. J Head Trauma Rehabil. 2016;31:215–24.CrossRefPubMed
41.
• Obenaus A, Ng M, Orantes AM, Kinney-Lang E, Rashid F, Hamer M, et al. Traumatic brain injury results in acute rarefication of the vascular network. Sci Rep. 2017;7:1–14 This study provides structural evidence that may explain the hemodynamic alterations reported after TBI by demonstrating with the use of novel vessel-painting technique. Ex-vivo analysis of post TBI ratios showed that there is a reduction in vascular network and vascular complexity both at the injury site and globally. CrossRef
42.
Yamakami I, McIntosh TK. Alterations in regional cerebral blood flow following brain injury in the rat. J Cereb Blood Flow Metab. 1991;11:655–60.CrossRefPubMed
43.
• Churchill NW, Hutchison MG, Richards D, Leung G, Graham SJ, Schweizer TA. The first week after concussion: blood flow, brain function and white matter microstructure. NeuroImage Clin. 2017;14:480–9 The Authors; This study used MRI to analyze CBF and global functional connectivity (Gconn) of grey matter, along with FA and mean diffusivity (MD) of white matter in adult athletes with mTBI during their first week post-injury. They showed blood flow decreased in the frontal and temporal lobes with functional blood flow effects seen in regions involved in autonomic regulation and emotion processing (cingulum, insula, and hippocampal gyri). CrossRefPubMedPubMedCentral
44.
Thibeault CM, Thorpe S, O’Brien MJ, Canac N, Ranjbaran M, Patanam I, et al. A cross-sectional study on cerebral hemodynamics after mild traumatic brain injury in a pediatric population. Front Neurol. 2018;9:200.CrossRefPubMedPubMedCentral
45.
Wang Y, Nelson LD, LaRoche AA, Pfaller AY, Nencka AS, Koch KM, et al. Cerebral blood flow alterations in acute sport-related concussion. J Neurotrauma. 2016;33:1227–36.CrossRefPubMedPubMedCentral
46.
Meier TB, Bellgowan PSF, Singh R, Kuplicki R, Polanski DW, Mayer AR. Recovery of cerebral blood flow following sports-related concussion. JAMA Neurol. 2015;72:530.CrossRefPubMed
47.
Rowson S, Bland ML, Campolettano ET, Press JN, Rowson B, Smith JA, et al. Biomechanical perspectives on concussion in sport. Sports Med Arthrosc. 2016;24:100–7.CrossRefPubMedPubMedCentral
48.
Choe MC, Valino H, Fischer J, Zeiger M, Breault J, McArthur DL, et al. Targeting the epidemic: interventions and follow-up are necessary in the pediatric traumatic brain injury clinic. J Child Neurol. 2016;31:109–15.CrossRefPubMed
49.
50.
Ahmadzadeh H, Smith DH, Shenoy VB. Viscoelasticity of tau proteins leads to strain rate-dependent breaking of microtubules during axonal stretch injury: predictions from a mathematical model. Biophys J Biophysical Society. 2014;106:1123–33.
51.
Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol. Elsevier Inc. 2013;246:35–43.CrossRefPubMed
52.
Nixon RA. The regulation of neurofilament protein dynamics by phosphorylation: clues to neurofibrillary pathobiology. Brain Pathol. 1993;3:29–38.CrossRefPubMed
53.
William L, Povlishock JT, Graham DL, Al MET. A mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma. 1997;14:419–40.CrossRef
54.
Pettus EH, Christman CW, Giebel ML, Povlishock JT. Traumatically induced altered membrane permeability: its relationship to traumatically induced reactive axonal change. J Neurotrauma. 1994;11:507–22.CrossRefPubMed
55.
Tang-Schomer MD, Johnson VE, Baas PW, Stewart W, Smith DH. Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. Exp Neurol. Elsevier Inc. 2012;233:364–72.CrossRefPubMed
56.
Gultekin SH, Smith TW. Diffuse axonal injury in craniocerebral trauma. A comparative histologic and immunohistochemical study. Arch Pathol Lab Med. 1994;118:168–71.PubMed
57.
Chen XH, Johnson VE, Uryu K, Trojanowski JQ, Smith DH. A lack of amyloid β plaques despite persistent accumulation of amyloid β in axons of long-term survivors of traumatic brain injury. Brain Pathol. 2009;19:214–23.CrossRefPubMed
58.
Prins ML, Hales A, Reger M, Giza CC, Hovda DA. Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments. Dev Neurosci. 2011;32:510–8.
59.
Reeves TM, Phillips LL, Povlishock JT. Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury. Exp Neurol. 2005;196:126–37.CrossRefPubMed
60.
• Fidan E, Foley LM, New LA, Alexander H, Kochanek PM, Hitchens TK, et al. Metabolic and structural imaging at 7 tesla after repetitive mild traumatic brain injury in immature rats. ASN Neuro. 2018;10:175909141877054 This study using DTI and H-MRS showed subtle structural (APP accumulation along with the decrease in choline and lipid markers) and metabolic alterations after mTBI and rmTBI in the immature brain. These findings reinforce evidence of concussive injury damage to axonal membranes, which may be relevant to understanding the extent of disability following mTBI and rmTBI in the immature brain. CrossRef
61.
Wozniak JR, Krach L, Ward E, Mueller BA, Muetzel R, Schnoebelen S, et al. Neurocognitive and neuroimaging correlates of pediatric traumatic brain injury: a diffusion tensor imaging (DTI) study. Arch Clin Neuropsychol. 2007;22:555–68.CrossRefPubMedPubMedCentral
62.
Mayer AR, Hanlon FM, Ling JM. Gray matter abnormalities in pediatric mild traumatic brain injury. J Neurotrauma. 2015;32:723–30.CrossRefPubMed
63.
Wilde EA, McCauley SR, Hunter JV, Bigler ED, Chu Z, Wang ZJ, et al. Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology. 2008;70:948–55.CrossRefPubMed
64.
Dennis EL, Ellis MU, Marion SD, Jin Y, Moran L, Olsen A, et al. Callosal function in pediatric traumatic brain injury linked to disrupted white matter integrity. J Neurosci. 2015;35:10202–11.CrossRefPubMedPubMedCentral
65.
•• Spader HS, Dean DC, LaFrance WC, Raukar NP, Cosgrove GR, Eyerly-Webb SA, et al. Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports. J Neurosurg. 2018;1–9. MWF at baseline was significantly higher in the bilateral basal ganglia, anterior and posterior corpora callosa, left corticospinal tract, and left anterior and superior temporal lobe in the brains of previously concussed athletes compared with the brains of controls. At 3 months after a concussive injury, MWF increase was also observed. These suggest acute/chronic MWF alterations in concussed athletes from previous injuries by theorizing possible re-myelination leading to hypermyelination.
66.
67.
Rosenzweig MR, Bennett EL. Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res. 1996;78:57–65.CrossRefPubMed
68.
Giza CC, Griesbach GS, Hovda DA. Experience-dependent behavioral plasticity is disturbed following traumatic injury to the immature brain. Behav Brain Res. 2005;157:11–22.CrossRefPubMed
69.
Aungst SL, Kabadi SV, Thompson SM, Stoica BA, Faden AI. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits. J Cereb Blood Flow Metab Nat Publ Group. 2014;34:1223–32.CrossRef
70.
Fineman I, Giza CC, Nahed BV, Lee SM, Hovda DA. Inhibition of neocortical plasticity during development by a moderate concussive brain injury. J Neurotrauma. 2000;17:739–49.CrossRefPubMed
71.
Sick TJ, Pérez-Pinzón MA, Feng ZZ. Impaired expression of long-term potentiation in hippocampal slices 4 and 48 h following mild fluid-percussion brain injury in vivo. Brain Res. 1998;785:287–92.CrossRefPubMed
72.
• White ER, Pinar C, Bostrom CA, Meconi A, Christie BR. Mild traumatic brain injury produces long-lasting deficits in synaptic plasticity in the female juvenile hippocampus. J Neurotrauma. 2017;34:1111–23 Compared to male counterparts, juvenile female rats undergoing closed-head mTBI model showed significant reduction in long-term potentiation (LTP) at 1 day which persisted to 28 days following injury. This basic science study provides evidence of gender dimorphism in the pathophysiology of mTBI. CrossRefPubMed
73.
Reeves TM, Lyeth BG, Povlishock JT. Long-term potentiation deficits and excitability changes following traumatic brain injury. Exp Brain Res. 1995;106:248–56.CrossRefPubMed
74.
Liu X, Qiu J, Alcon S, Hashim J, Meehan WP, Mannix R. Environmental enrichment mitigates deficits after repetitive mild traumatic brain injury. J Neurotrauma. 2017;34:2445–55.CrossRefPubMedPubMedCentral
75.
De Beaumont L, Tremblay S, Poirier J, Lassonde M, Théoret H. Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes. Cereb Cortex. 2012;22:112–21.CrossRefPubMed
76.
Majerske CW, Mihalik JP, Ren D, Collins MW, Reddy CC, Lovell MR, et al. Concussion in sports: postconcussive activity levels, symptoms, and neurocognitive performance. J Athl Train. 2008;43:265.CrossRefPubMedPubMedCentral
77.
• Rathbone ATL, Tharmaradinam S, Jiang S, Rathbone MP, Kumbhare DA. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: introduction of the “post-inflammatory brain syndrome” PIBS. Brain Behav Immun. 2015;46:1–16 Elsevier Inc. This review article summarizes the current evidence to support the notion of neuroinflammation in post-concussion syndrome (PCS) and the potential role systemic inflammation plays in post-concussive-like symptoms. This is the first article to introduce post-inflammatory brain syndrome (PIBS) as a unifying term to describe common outcomes of many different inflammatory insults. CrossRefPubMed
78.
79.
• Villapol S, Loane DJ, Burns MP. Sexual dimorphism in the inflammatory response to traumatic brain injury. Glia. 2017;65:1423–38 mTBI in male mice caused a rapid and pronounced cortical microglia/macrophage activation in male mice with a prominent activated phenotype with sustained peak from 1 to 7 days. In contrast, TBI promoted a weaker microglia/macrophage phenotype activation in females with biphasic pro-inflammatory peaks at 4 h and 7 days, and delayed anti-inflammatory peak at 30 days. This basic science study provides further evidence of gender dimorphism in the pathophysiology of mTBI. CrossRefPubMedPubMedCentral
80.
Redell JB, Moore AN, Grill RJ, Johnson D, Zhao J, Liu Y, et al. Analysis of functional pathways altered after mild traumatic brain injury. J Neurotrauma. 2013;30:752–64.CrossRefPubMedPubMedCentral
81.
Bélanger M, Allaman I, Magistretti PJ. Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes. J Neurochem. 2011;116:564–76.CrossRefPubMed
82.
Blaylock RL, Maroon JC. Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy—a unifying hypothesis. Surg Neurol Int. 2011;2:107.CrossRefPubMedPubMedCentral
83.
Su SH, Xu W, Li M, Zhang L, Wu YF, Yu F, et al. Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: a preliminary study. Brain Behav Immun. Elsevier Inc. 2014;38:111–7.CrossRefPubMed
84.
Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7:41–53.CrossRefPubMed
85.
Yeung D, Manias JL, Stewart DJ, Nag S. Decreased junctional adhesion molecule-a expression during blood-brain barrier breakdown. Acta Neuropathol. 2008;115:635–42.CrossRefPubMed
86.
Nag S, Manias JL, Stewart DJ. Expression of endothelial phosphorylated caveolin-1 is increased in brain injury. Neuropathol Appl Neurobiol. 2009;35:417–26.CrossRefPubMed
87.
Barzó P, Marmarou A, Fatouros P, Corwin F, Dunbar J. Magnetic resonance imaging-monitored acute blood-brain barrier changes in experimental traumatic brain injury. J Neurosurg. 1996;85:1113–21.CrossRefPubMed
88.
Habgood MD, Bye N, Dziegielewska KM, Ek CJ, Lane MA, Potter A, et al. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci. 2007;25:231–8.CrossRefPubMed
89.
Baldwin SA, Fugaccia I, Brown DR, Brown LV, Scheff SW. Blood-brain barrier breach following cortical contusion in the rat. J Neurosurg. 1996;85:476–81.CrossRefPubMed
90.
Başkaya MK, Rao AM, Doğan A, Donaldson D, Dempsey RJ. The biphasic opening of the blood-brain barrier in the cortex and hippocampus after traumatic brain injury in rats. Neurosci Lett. 1997;226:33–6.CrossRefPubMed
91.
Hay JR, Johnson VE, Young AMH, Smith DH, Stewart W. Blood-brain barrier disruption is an early event that may persist for many years after traumatic brain injury in humans. J Neuropathol Exp Neurol. 2015;74:1147–57.PubMed
92.
Johnson VE, Weber MT, Xiao R, Cullen DK, Meaney DF, Stewart W, et al. Mechanical disruption of the blood–brain barrier following experimental concussion. Acta Neuropathol. 2018;135:711–26.CrossRefPubMedPubMedCentral
93.
Raghupathi R, Conti AC, Graham DI, Krajewski S, Reed JC, Grady MS, et al. Mild traumatic brain injury induces apoptotic cell death in the cortex that is preceded by decreases in cellular Bcl-2 immunoreactivity. Neuroscience. 2002;110:605–16.CrossRefPubMed
94.
Shlosberg D, Benifla M, Kaufer D, Friedman A. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol Nature Publishing Group. 2010;6:393–403.CrossRef
95.
Korn A, Golan H, Melamed I, Pascual-marqui R, Friedman A. Focal cortical dysfunction and blood – brain barrier disruption in patients with postconcussion syndrome. 2005;22:1–9.
96.
Weissberg I, Veksler R, Kamintsky L, Saar-Ashkenazy R, Milikovsky DZ, Shelef I, et al. Imaging blood-brain barrier dysfunction in football players. JAMA Neurol. 2014;71:1453–5.CrossRefPubMed
97.
Livingston WS, Gill JM, Cota MR, Olivera A, O’Keefe JL, Martin C, et al. Differential gene expression associated with meningeal injury in acute mild traumatic brain injury. J Neurotrauma. 2017;34:853–60.CrossRefPubMedPubMedCentral
98.
Gurkoff GG, Giza CC, Hovda DA. Lateral fluid percussion injury in the developing rat causes an acute, mild behavioral dysfunction in the absence of significant cell death. Brain Res. 2006;1077:24–36.CrossRefPubMed
99.
Lyeth BG, Jenkins LW, Hamm RJ, Dixon CE, Phillips LL, Clifton GL, et al. Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain Res. 1990;526:249–58.CrossRefPubMed
100.
Dikranian K, Cohen R, Mac Donald C, Pan Y, Brakefield D, Bayly P, et al. Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons. Exp Neurol. 2008;211:551–60.CrossRefPubMedPubMedCentral
101.
Smith DH, Chen X-H, Pierce JES, Wolf JA, Trojanowski JQ, Graham DI, et al. Progressive atrophy and neuron death for one year following brain trauma in the rat. J Neurotrauma. 1997;14:715–27.CrossRefPubMed
102.
Pullela R, Raber J, Pfankuch T, Ferriero DM, Claus CP, Koh SE, et al. Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments. Dev Neurosci. 2006;28:396–409.CrossRefPubMed
103.
Zhou Y, Kierans A, Kenul D, Ge Y, Rath J, Reaume J, et al. Mild traumatic brain injury: longitudinal regional brain volume changes. Radiology. 2013;267:880–90.CrossRefPubMedPubMedCentral
104.
Monti JM, Voss MW, Pence A, McAuley E, Kramer AF, Cohen NJ. History of mild traumatic brain injury is associated with deficits in relational memory, reduced hippocampal volume, and less neural activity later in life. Front Aging Neurosci. 2013;5:1–9.CrossRef
105.
McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136:43–64.CrossRefPubMed
106.
Singh R, Meier TB, Kuplicki R, Savitz J, Mukai I, Cavanagh LM, et al. Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes. J Am Med Assoc. 2014;311:1883–8.CrossRef
107.
Zagorchev L, Meyer C, Stehle T, Wenzel F, Young S, Peters J, et al. Differences in regional brain volumes two months and one year after mild traumatic brain injury. J Neurotrauma. 2016;33:29–34.CrossRefPubMedPubMedCentral
108.
109.
110.
Nahum AM, Smith R, Ward CC. Intracranial pressure dynamics during head impact. Proceedings, 21st Stapp Car Crash Conf., SAE Paper No. 770922. 1977.
111.
Thibault LE, Meaney DF, Anderson BJ, Marmarou A. Biomechanical aspects of a fluid percussion model of brain injury. J Neurotrauma. 1992;9:311–22.CrossRefPubMed
112.
Prange MT, Meaney DF, Margulies SS. Defining brain mechanical properties: effects of region, direction, and species. Stapp Car Crash J. 2000;44:205–13.PubMed
113.
Adams JH, Graham DI, Murray LS, Scott G. Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases. Ann Neurol. 1982;12:557–63.CrossRefPubMed
114.
Ommaya AK, Hirsch AE, Martinez JL. The role of whiplash in cerebral concussion. Proceedings of the 10th Stapp Car Crash Conference. 1996;314–3243.
115.
Kimpara H, Iwamoto M. Mild traumatic brain injury predictors based on angular accelerations during impacts. Ann Biomed Eng. 2012;40:114–26.CrossRefPubMed
116.
Rowson S, Duma SM, Beckwith JG, Chu JJ, Greenwald RM, Crisco JJ, et al. Rotational head kinematics in football impacts: an injury risk function for concussion. Ann Biomed Eng. 2012;40:1–13.CrossRefPubMed
117.
Post A, Blaine HT. Rotational acceleration, brain tissue strain, and the relationship to concussion. J Biomech Eng. 2015;137:030801.CrossRef
118.
Kerr ZY, Roos KG, Djoko A, Dalton SL, Broglio SP, Marshall SW, et al. Epidemiologic measures for quantifying the incidence of concussion in national collegiate athletic association sports. J Athl Train. 2017;52:167–74.CrossRefPubMedPubMedCentral
119.
Cobb BR, Urban JE, Davenport EM, Rowson S, Duma SM, Maldjian JA, et al. Head impact exposure in youth football: elementary school ages 9–12 years and the effect of practice structure. Ann Biomed Eng. 2013;41:2463–73.CrossRefPubMedPubMedCentral
120.
Manoogian S, McNeely D, Duma S, Brolinson G, Greenwald R. Head acceleration is less than 10 percent of helmet acceleration in football impacts. Biomed Sci Instrum. 2006;42:383–8.PubMed
121.
Wu LC, Nangia V, Bui K, Hammoor B, Kurt M, Hernandez F, et al. In vivo evaluation of wearable head impact sensors. Ann Biomed Eng. 2016;44:1234–45.CrossRefPubMed
122.
Press JN, Rowson S. Quantifying head impact exposure in collegiate women’s soccer. Clin J Sport Med. 2017;27:104–10.CrossRefPubMed
123.
McCrory P, Feddermann-Demont N, Dvořák J, Cassidy JD, McIntosh A, Vos PE, et al. What is the definition of sports-related concussion: a systematic review. Br J Sports Med. 2017;51:877–87.CrossRefPubMed
124.
Brennan JH, Mitra B, Synnot A, McKenzie J, Willmott C, McIntosh AS, et al. Accelerometers for the assessment of concussion in male athletes: a systematic review and meta-analysis. Sport Med Springer International Publishing. 2017;47:469–78.
125.
Beckwith JG, Greenwald RM, Chu JJ, Crisco JJ, Rowson S, Duma SM, et al. Timing of concussion diagnosis is related to head impact exposure prior to injury. Med Sci Sports Exerc. 2013;45:747–54.CrossRefPubMedPubMedCentral
126.
•• Rowson S, Duma SM, Stemper BD, Shah A, Mihalik JP, Harezlak J, et al. Correlation of concussion symptom profile with head impact biomechanics: a case for individual-specific injury tolerance. J Neurotrauma. 2018;35:681–90 This study showed no link between biomechanical input and symptom presentation (by measure of SCAT3 and symptom resolution time) for concussed subjects. Authors also found concussive impacts were among the most severe for each individual player. This study is one of the first to theorize an individual-specific tolerance to head acceleration, suggesting similar biomechanical inputs can produce different injury presentations. CrossRefPubMed
127.
128.
Caccese JB, Buckley TA, Tierney RT, Arbogast KB, Rose WC, Glutting JJ, et al. Head and neck size and neck strength predict linear and rotational acceleration during purposeful soccer heading. Sport Biomech Routledge. 2017;3141:1–15.
Metadata
Title
Concussion Pathophysiology and Injury Biomechanics
Authors
Rafael Romeu-Mejia
Christopher C. Giza
Joshua T. Goldman
Publication date
01-06-2019
Publisher
Springer US
Published in
Current Reviews in Musculoskeletal Medicine / Issue 2/2019
Electronic ISSN: 1935-9748
DOI
https://doi.org/10.1007/s12178-019-09536-8

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