An overview of the basic science of concussion and subconcussion: Where we are and where we are going

Neurosurgical Focus

Volumn 33, Issue 6, 2012, Pages

  Dashnaw, Matthew L ^a   Petraglia, Anthony L ^a   Bailes, Julian E ^b  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b NORTHSHORE UNIVERSITY HEALTHSYSTEM   (United States)

Author keywords

Chronic traumatic encephalopathy; Concussion; Pathophysiology; Subconcussion; Traumatic brain injury

Indexed keywords

ANIMAL; BIOPHYSICS; BRAIN CONCUSSION; HUMAN; INJURY SCALE; METHODOLOGY; NEUROLOGY; PATHOPHYSIOLOGY; REVIEW; SPORT INJURY;

ANIMALS; ATHLETIC INJURIES; BIOPHYSICS; BRAIN CONCUSSION; HUMANS; NEUROLOGY; TRAUMA SEVERITY INDICES;

EID: 84872846127     PISSN: None     EISSN: 10920684     Source Type: Journal    
DOI: 10.3171/2012.10.FOCUS12284     Document Type: Article

References (110)

1. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR: Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15:49-59, 1989
2. Allen GV, Gerami D, Esser MJ: Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury. Neuroscience 99:93-105, 2000
3. Andrew RD: Seizure and acute osmotic change: clinical and neurophysiological aspects. J Neurol Sci 101:7-18, 1991
4. Bayly PV, Cohen TS, Leister EP, Ajo D, Leuthardt EC, Genin GM: Deformation of the human brain induced by mild acceleration. J Neurotrauma 22:845-856, 2005
5. Bazarian JJ, Zhu T, Blyth B, Borrino A, Zhong J: Subjectspecific changes in brain white matter on diffusion tensor imaging after sports-related concussion. Magn Reson Imaging 30:171-180, 2012
6. Bennett RE, Mac Donald CL, Brody DL: Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury. Neurosci Lett 513:160-165, 2012
7. Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, et al: Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86:241-251, 1997
8. Blaylock RL, Maroon J: Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy-a unifying hypothesis. Surg Neurol Int 2:107, 2011
9. Block ML, Zecca L, Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57-69, 2007
10. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ: Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344:1055-1056, 1994
11. Breedlove EL, Robinson M, Talavage TM, Morigaki KE, Yoruk U, O'Keefe K, et al: Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high school football. J Biomech 45:1265-1272, 2012
12. Broglio SP, Eckner JT, Martini D, Sosnoff JJ, Kutcher JS, Randolph C: Cumulative head impact burden in high school football. J Neurotrauma 28:2069-2078, 2011
13. Conte V, Uryu K, Fujimoto S, Yao Y, Rokach J, Longhi L, et al: Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury. J Neurochem 90:758-764, 2004
14. Creeley CE, Wozniak DF, Bayly PV, Olney JW, Lewis LM: Multiple episodes of mild traumatic brain injury result in impaired cognitive performance in mice. Acad Emerg Med 11:809-819, 2004
15. Crisco JJ, Fiore R, Beckwith JG, Chu JJ, Brolinson PG, Duma S, et al: Frequency and location of head impact exposures in individual collegiate football players. J Athl Train 45:549-559, 2010
16. Cubon VA, Putukian M, Boyer C, Dettwiler A: A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion. J Neurotrauma 28:189-201, 2011
17. Davis GA, Iverson GL, Guskiewicz KM, Ptito A, Johnston KM: Contributions of neuroimaging, balance testing, electrophysiology and blood markers to the assessment of sport-related concussion. Br J Sports Med 43 (Suppl 1):i36-i45, 2009
18. 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 19:427-438, 2002
19. Doezema D, King JN, Tandberg D, Espinosa MC, Orrison WW: Magnetic resonance imaging in minor head injury. Ann Emerg Med 20:1281-1285, 1991
20. Engel S, Wehner HD, Meyermann R: Expression of microglial markers in the human CNS after closed head injury. Acta Neurochir Suppl 66:89-95, 1996
21. Faden AI, Demediuk P, Panter SS, Vink R: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:798-800, 1989
22. Farkas O, Lifshitz J, Povlishock JT: Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J Neurosci 26:3130-3140, 2006
23. Friess SH, Ichord RN, Ralston J, Ryall K, Helfaer MA, Smith C, et al: Repeated traumatic brain injury affects composite cognitive function in piglets. J Neurotrauma 26:1111-1121, 2009
24. Gentry LR, Godersky JC, Thompson B: MR imaging of head trauma: review of the distribution and radiopathologic features of traumatic lesions. AJR Am J Roentgenol 150:663-672, 1988
25. Ghirnikar RS, Lee YL, Eng LF: Inflammation in traumatic brain injury: role of cytokines and chemokines. Neurochem Res 23:329-340, 1998
26. Ginsberg MD, Zhao W, Alonso OF, Loor-Estades JY, Dietrich WD, Busto R: Uncoupling of local cerebral glucose metabolism and blood flow after acute fluid-percussion injury in rats. Am J Physiol 272:H2859-H2868, 1997
27. Guskiewicz KM, Mihalik JP, Shankar V, Marshall SW, Crowell DH, Oliaro SM, et al: Measurement of head impacts in collegiate football players: relationship between head impact biomechanics and acute clinical outcome after concussion. Neurosurgery 61:1244-1253, 2007
28. Gysland SM, Mihalik JP, Register-Mihalik JK, Trulock SC, Shields EW, Guskiewicz KM: The relationship between subconcussive impacts and concussion history on clinical measures of neurologic function in collegiate football players. Ann Biomed Eng 40:14-22, 2012
29. Henry LC, Tremblay J, Tremblay S, Lee A, Brun C, Lepore N, et al: Acute and chronic changes in diffusivity measures after sports concussion. J Neurotrauma 28:2049-2059, 2011
30. Herman ST: Epilepsy after brain insult: targeting epileptogenesis. Neurology 59 (9 Suppl 5):S21-S26, 2002
31. Hofman PA, Stapert SZ, van Kroonenburgh MJ, Jolles J, de Kruijk J, Wilmink JT: MR imaging, single-photon emission CT, and neurocognitive performance after mild traumatic brain injury. AJNR Am J Neuroradiol 22:441-449, 2001
32. Homsi S, Piaggio T, Croci N, Noble F, Plotkine M, Marchand-Leroux C, et al: Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelveweek follow-up study. J Neurotrauma 27:911-921, 2010
33. Hootman JM, Dick R, Agel J: Epidemiology of collegiate injuries for 15 sports: summary and recommendations for injury prevention initiatives. J Athl Train 42:311-319, 2007
34. Hovda DA, Yoshino A, Kawamata T, Katayama Y, Becker DP: Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study. Brain Res 567:1-10, 1991
35. Hughes DG, Jackson A, Mason DL, Berry E, Hollis S, Yates DW: Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology 46:550-558, 2004
36. Kalimo H, Rehncrona S, Söderfeldt B: The role of lactic acidosis in the ischemic nerve cell injury. Acta Neuropathol Suppl 7:20-22, 1981
37. Kanayama G, Takeda M, Niigawa H, Ikura Y, Tamii H, Taniguchi N, et al: The effects of repetitive mild brain injury on cytoskeletal protein and behavior. Methods Find Exp Clin Pharmacol 18:105-115, 1996
38. Kane MJ, Angoa-Pérez M, Briggs DI, Viano DC, Kreipke CW, Kuhn DM: A mouse model of human repetitive mild traumatic brain injury. J Neurosci Methods 203:41-49, 2012
39. 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 73:889-900, 1990
40. Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP: Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab 12:12-24, 1992
41. Khuman J, Meehan WP III, Zhu X, Qiu J, Hoffmann U, Zhang J, et al: Tumor necrosis factor alpha and Fas receptor contribute to cognitive deficits independent of cell death after concussive traumatic brain injury in mice. J Cereb Blood Flow Metab 31:778-789, 2011
42. Korn A, Golan H, Melamed I, Pascual-Marqui R, Friedman A: Focal cortical dysfunction and blood-brain barrier disruption in patients with postconcussion syndrome. J Clin Neurophysiol 22:1-9, 2005
43. Laurer HL, Bareyre FM, Lee VM, Trojanowski JQ, Longhi L, Hoover R, et al: Mild head injury increasing the brain's vulnerability to a second concussive impact. J Neurosurg 95:859-870, 2001
44. Le TH, Gean AD: Neuroimaging of traumatic brain injury. Mt Sinai J Med 76:145-162, 2009
45. Lee H, Wintermark M, Gean AD, Ghajar J, Manley GT, Mukherjee P: Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 25:1049-1056, 2008
46. Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, et al: Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil 22:141-155, 2007
47. Lifshitz J, Sullivan PG, Hovda DA, Wieloch T, McIntosh TK: Mitochondrial damage and dysfunction in traumatic brain injury. Mitochondrion 4:705-713, 2004
48. Longhi L, Saatman KE, Fujimoto S, Raghupathi R, Meaney DF, Davis J, et al: Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery 56:364-374, 2005
49. Luther N, Niogi S, Kutner K, Rodeo S, Shetty T, Warren R, et al: 143 Diffusion tensor and susceptibility-weighted imaging in concussion assessment of National Football League players. Neurosurgery 71:E558, 2012
50. 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 87:9-19, 1997
51. Maruta J, Lee SW, Jacobs EF, Ghajar J: A unified science of concussion. Ann N Y Acad Sci 1208:58-66, 2010
52. Masuzawa H, Nadamura N, Hirakawa K, Sano K, Matsuno M: Experimental head injury & concussion in monkey using pure linear acceleration impact. Neurol Med Chir (Tokyo) 16:77-90, 1976
53. Maugans TA, Farley C, Altaye M, Leach J, Cecil KM: Pediatric sports-related concussion produces cerebral blood flow alterations. Pediatrics 129:28-37, 2012
54. Maxwell WL, Graham DI: Loss of axonal microtubules and neurofilaments after stretch-injury to guinea pig optic nerve fibers. J Neurotrauma 14:603-614, 1997
55. McCrory PR, Berkovic SF: Video analysis of acute motor and convulsive manifestations in sport-related concussion. Neurology 54:1488-1491, 2000
56. McCullough BJ, Jarvik JG: Diagnosis of concussion: the role of imaging now and in the future. Phys Med Rehabil Clin N Am 22:635-652, viii, 2011
57. Meehan WP III, Bachur RG: Sport-related concussion. Pediatrics 123:114-123, 2009
58. Meehan WP III, Zhang J, Mannix R, Whalen MJ: Increasing recovery time between injuries improves cognitive outcome after repetitive mild concussive brain injuries in mice. Neurosurgery 71:885-892, 2012
59. Mendez CV, Hurley RA, Lassonde M, Zhang L, Taber KH: Mild traumatic brain injury: neuroimaging of sports-related concussion. J Neuropsychiatry Clin Neurosci 17:297-303, 2005
60. Miller JR, Adamson GJ, Pink MM, Sweet JC: Comparison of preseason, midseason, and postseason neurocognitive scores in uninjured collegiate football players. Am J Sports Med 35: 1284-1288, 2007
61. Mills JD, Bailes JE, Sedney CL, Hutchins H, Sears B: Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. Laboratory investigation. J Neurosurg 114:77-84, 2011
62. Mills JD, Hadley K, Bailes JE: Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury. Neurosurgery 68:474-481, 2011
63. Muir JK, Boerschel M, Ellis EF: Continuous monitoring of posttraumatic cerebral blood flow using laser-Doppler flowmetry. J Neurotrauma 9:355-362, 1992
64. Nakajima Y, Horiuchi Y, Kamata H, Yukawa M, Kuwabara M, Tsubokawa T: Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats. Tohoku J Exp Med 221:229-235, 2010
65. Nakamura Y, Takeda M, Angelides KJ, Tanaka T, Tada K, Nishimura T: Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro. Biochem Biophys Res Commun 169: 744-750, 1990
66. Nilsson P, Ronne-Engström E, Flink R, Ungerstedt U, Carlson H, Hillered L: Epileptic seizure activity in the acute phase following cortical impact trauma in rat. Brain Res 637:227-232, 1994
67. Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R, et al: Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 29: 967-973, 2008
68. Nixon RA: The regulation of neurofilament protein dynamics by phosphorylation: clues to neurofibrillary pathobiology. Brain Pathol 3:29-38, 1993
69. Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH: Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 57:128-134, 2005
70. Ommaya AK, Corrao P, Letcher FS: Head injury in the chimpanzee. 1. Biodynamics of traumatic unconsciousness. J Neurosurg 39:152-166, 1973
71. Ommaya AK, Hirsch AE: Tolerances for cerebral concussion from head impact and whiplash in primates. J Biomech 4:13-21, 1971
72. Oppenheimer DR: Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiatry 31:299-306, 1968
73. Pellman EJ, Viano DC, Tucker AM, Casson IR, Waeckerle JF: Concussion in professional football: reconstruction of game impacts and injuries. Neurosurgery 53:799-814, 2003
74. Povlishock JT, Becker DP, Cheng CL, Vaughan GW: Axonal change in minor head injury. J Neuropathol Exp Neurol 42:225-242, 1983
75. Povlishock JT, Christman CW: The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J Neurotrauma 12:555-564, 1995
76. Raghupathi R, Mehr MF, Helfaer MA, Margulies SS: Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig. J Neurotrauma 21:307-316, 2004
77. Rancan M, Otto VI, Hans VH, Gerlach I, Jork R, Trentz O, et al: Upregulation of ICAM-1 and MCP-1 but not of MIP-2 and sensorimotor deficit in response to traumatic axonal injury in rats. J Neurosci Res 63:438-446, 2001
78. Ransohoff RM, Perry VH: Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119-145, 2009
79. Rhodes JKJ, Sharkey J, Andrews PJD: The temporal expression, cellular localization, and inhibition of the chemokines MIP-2 and MCP-1 after traumatic brain injury in the rat. J Neurotrauma 26:507-525, 2009
80. Robertson CL, Saraswati M, Fiskum G: Mitochondrial dysfunction early after traumatic brain injury in immature rats. J Neurochem 101:1248-1257, 2007
81. Rosen AS, Andrew RD: Osmotic effects upon excitability in rat neocortical slices. Neuroscience 38:579-590, 1990
82. 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 40:1-13, 2012
83. Saatman KE, Abai B, Grosvenor A, Vorwerk CK, Smith DH, Meaney DF: Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice. J Cereb Blood Flow Metab 23:34-42, 2003
84. Saly V, Andrew RD: CA3 neuron excitation and epileptiform discharge are sensitive to osmolality. J Neurophysiol 69: 2200-2208, 1993
85. Sass DJ, Corrao P, Ommaya AK: Brain motion during vibration of water immersed rhesus monkeys. J Biomech 4:331-334, 1971
86. Scheid R, Walther K, Guthke T, Preul C, von Cramon DY: Cognitive sequelae of diffuse axonal injury. Arch Neurol 63: 418-424, 2006
87. Schnebel B, Gwin JT, Anderson S, Gatlin R: In vivo study of head impacts in football: a comparison of National Collegiate Athletic Association Division I versus high school impacts. Neurosurgery 60:490-496, 2007
88. Schwartzkroin PA, Baraban SC, Hochman DW: Osmolarity, ionic flux, and changes in brain excitability. Epilepsy Res 32:275-285, 1998
89. Sekino H, Nakamura N, Kanda R, Yasue M, Masuzawa H, Aoyagi N, et al: [Experimental head injury in monkeys using rotational acceleration impact (author's transl).] Neurol Med Chir (Tokyo) 20:127-136, 1980 (Jpn)
90. Shapira Y, Setton D, Artru AA, Shohami E: Blood-brain barrier permeability, cerebral edema, and neurologic function after closed head injury in rats. Anesth Analg 77:141-148, 1993
91. Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, Rathi Y, et al: A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging Behav 6:137-192, 2012
92. Shitaka Y, Tran HT, Bennett RE, Sanchez L, Levy MA, Dikranian K, et al: Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J Neuropathol Exp Neurol 70:551-567, 2011
93. Shlosberg D, Benifla M, Kaufer D, Friedman A: Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Nephrol 6:393-403, 2010
94. Shultz SR, MacFabe DF, Foley KA, Taylor R, Cain DP: Subconcussive brain injury in the Long-Evans rat induces acute neuroinflammation in the absence of behavioral impairments. Behav Brain Res 229:145-152, 2012
95. Smith DH, Meaney DF, Shull WH: Diffuse axonal injury in head trauma. J Head Trauma Rehabil 18:307-316, 2003
96. Smith DW, Bailes JE, Fisher JA, Robles J, Turner RC, Mills JD: Internal jugular vein compression mitigates traumatic axonal injury in a rat model by reducing the intracranial slosh effect. Neurosurgery 70:740-746, 2012
97. Spain A, Daumas S, Lifshitz J, Rhodes J, Andrews PJD, Horsburgh K, et al: Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury. J Neurotrauma 27: 1429-1438, 2010
98. Sternberger LA, Sternberger NH: Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A 80:6126-6130, 1983
99. Suwanwela C, Suwanwela N: Intracranial arterial narrowing and spasm in acute head injury. J Neurosurg 36:314-323, 1972
100. Talavage TM, Nauman E, Breedlove EL, Yoruk U, Dye AE, Morigaki K, et al: Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion. J Neurotrauma [epub ahead of print], 2010
101. Uryu K, Laurer H, McIntosh T, Praticò D, Martinez D, Leight S, et al: Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J Neurosci 22:446-454, 2002
102. Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP: Mitochondrial dysfunction after experimental and human brain injury and its possible reversal with a selective N-type calcium channel antagonist (SNX-111). Neurol Res 19:334-339, 1997
103. Voller B, Benke T, Benedetto K, Schnider P, Auff E, Aichner F: Neuropsychological, MRI and EEG findings after very mild traumatic brain injury. Brain Inj 13:821-827, 1999
104. Weber JT: Experimental models of repetitive brain injuries. Prog Brain Res 161:253-261, 2007
105. Xiong Y, Gu Q, Peterson PL, Muizelaar JP, Lee CP: Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma 14:23-34, 1997
106. Yamakami I, McIntosh TK: Effects of traumatic brain injury on regional cerebral blood flow in rats as measured withradio labeled microspheres. J Cereb Blood Flow Metab 9: 117-124, 1989
107. Yarnell P, Ommaya AK: Experimental cerebral concussion in the rhesus monkey. Bull N Y Acad Med 45:39-45, 1969
108. 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 561:106-119, 1991
109. Yoshiyama Y, Uryu K, Higuchi M, Longhi L, Hoover R, Fujimoto S, et al: Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. J Neurotrauma 22:1134-1141, 2005
110. Zhang K, Johnson B, Pennell D, Ray W, Sebastianelli W, Slobounov S: Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study. Exp Brain Res 204:57-70, 201