Download PDF
Semin Neurol 2015; 35(01): 012-019
DOI: 10.1055/s-0035-1544240
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuropathology of Traumatic Brain Injury: Comparison of Penetrating, Nonpenetrating Direct Impact and Explosive Blast Etiologies

Nihal C. de Lanerolle
1   Department of Neurosurgery and Neurobiology, Yale School of Medicine, New Haven, Connecticut
,
Jung H. Kim
2   Department of Pathology, Yale School of Medicine, New Haven, Connecticut
,
Faris A. Bandak
3   Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland
› Author Affiliations
Further Information

Publication History

Publication Date:
25 February 2015 (online)

    Permissions and Reprints

Abstract

The neuropathology of traumatic brain injury (TBI) from various causes in humans is not as yet fully understood. The authors review and compare the known neuropathology in humans with severe, moderate, and mild TBI (mTBI) from nonpenetrating closed head injury (CHI) from blunt impacts and explosive blasts, as well as penetrating head injury (PHI). Penetrating head injury and CHI that are moderate to severe are more likely than mTBI to cause gross disruption of the cerebral vasculature. Axonal injury is classically exhibited as diffuse axonal injury (DAI) in severe to moderate CHI. Diffuse axonal injury is also prevalent in PHI. It is less so in mTBI. There may be a unique pattern of periventricular axonal injury in explosive blast mTBI. Neuronal injury is more prevalent in PHI and moderate to severe CHI than mTBI. Astrocyte and microglial activation and proliferation are found in all forms of animal TBI models and in severe to moderate TBI in humans. Their activation in mTBI in the human brain has not yet been studied.

Keywords

traumatic brain Injury - neuropathology - penetrating injury - closed head injury - explosive blast - concussion - microglia - astrocytes - diffuse axonal injury
 

  • References

  • 1 Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2 (7872) 81-84
    CrossrefPubMedGoogle Scholar
  • 2 Smith C. Review: the long-term consequences of microglial activation following acute traumatic brain injury. Neuropathol Appl Neurobiol 2013; 39 (1) 35-44
    CrossrefPubMedGoogle Scholar
  • 3 Blennow K, Hardy J, Zetterberg H. The neuropathology and neurobiology of traumatic brain injury. Neuron 2012; 76 (5) 886-899
    CrossrefPubMedGoogle Scholar
  • 4 Blumbergs PC, Reilly P, Vink R. Trauma. In: Love S, Jouis DN, Ellison DW, , eds. Greenfields Neuropathology. London, UK: Edward Arnold; 2008: 733-832
    Google Scholar
  • 5 Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ. Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 1995; 12 (4) 565-572
    CrossrefPubMedGoogle Scholar
  • 6 Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 1989; 15 (1) 49-59
    CrossrefPubMedGoogle Scholar
  • 7 Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW. Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 1993; 160 (2) 139-144
    CrossrefPubMedGoogle Scholar
  • 8 Hortobágyi T, Wise S, Hunt N , et al. Traumatic axonal damage in the brain can be detected using beta-APP immunohistochemistry within 35 min after head injury to human adults. Neuropathol Appl Neurobiol 2007; 33 (2) 226-237
    CrossrefPubMedGoogle Scholar
  • 9 Geddes JF, Whitwell HL, Graham DI. Traumatic axonal injury: practical issues for diagnosis in medicolegal cases. Neuropathol Appl Neurobiol 2000; 26 (2) 105-116
    CrossrefPubMedGoogle Scholar
  • 10 Cammermeyer J. The importance of avoiding “dark” neurons in experimental neuropathology. Acta Neuropathol 1961; 1: 245-270
    CrossrefPubMedGoogle Scholar
  • 11 Jortner BS. The return of the dark neuron. A histological artifact complicating contemporary neurotoxicologic evaluation. Neurotoxicology 2006; 27 (4) 628-634
    CrossrefPubMedGoogle Scholar
  • 12 Oehmichen M, Meissner C, König HG. Brain injury after gunshot wounding: morphometric analysis of cell destruction caused by temporary cavitation. J Neurotrauma 2000; 17 (2) 155-162
    CrossrefPubMedGoogle Scholar
  • 13 Oehmichen M, Meissner C, König HG. Brain injury after survived gunshot to the head: reactive alterations at sites remote from the missile track. Forensic Sci Int 2001; 115 (3) 189-197
    CrossrefPubMedGoogle Scholar
  • 14 Oehmichen M, Meissner C, König HG, Gehl H-B. Gunshot injuries to the head and brain caused by low-velocity handguns and rifles. A review. Forensic Sci Int 2004; 146 (2-3) 111-120
    PubMedGoogle Scholar
  • 15 Koszyca B, Blumbergs PC, Manavis J , et al. Widespread axonal injury in gunshot wounds to the head using amyloid precursor protein as a marker. J Neurotrauma 1998; 15 (9) 675-683
    CrossrefPubMedGoogle Scholar
  • 16 Bakir A, Temiz C, Umur S, Aydin V, Torun F. High-velocity gunshot wounds to the head: analysis of 135 patients. Neurol Med Chir (Tokyo) 2005; 45 (6) 281-287 , discussion 287
    CrossrefPubMedGoogle Scholar
  • 17 Adams JH, Graham DI, Scott G, Parker LS, Doyle D. Brain damage in fatal non-missile head injury. J Clin Pathol 1980; 33 (12) 1132-1145
    CrossrefPubMedGoogle Scholar
  • 18 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 1994; 344 (8929) 1055-1056
    CrossrefPubMedGoogle Scholar
  • 19 Stevens MC, Lovejoy D, Kim J, Oakes H, Kureshi I, Witt ST. Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury. Brain Imaging Behav 2012; 6 (2) 293-318
    CrossrefPubMedGoogle Scholar
  • 20 Ling G, Eklund J, Bandak FA. Blast brain injury from explosive blast: description and clinical management. In: Grafman J, Salazar AM, , eds. Handbook of Clinical Neurology. Amsterdam: Elsevier; 2015
    Google Scholar
  • 21 Cramer F, Paster S, Stephenson C. Cerebral injuries due to explosion waves, cerebral blast concussion; a pathologic, clinical, and electroencephalographic study. Archives Neurol Psychiatr 1949; 61: 1-20
    PubMedGoogle Scholar
  • 22 Hirsch AE, Ommaya AK. Head injury caused by underwater explosion of a firecracker. Case report. J Neurosurg 1972; 37 (1) 95-99
    CrossrefPubMedGoogle Scholar
  • 23 Mott FW. The microscopic examination of the brains of two men dead of commotio cerebri (shell shock) without visible external injury. J R Army Med Corps 1917; 29: 662-677
    PubMedGoogle Scholar
  • 24 Murthy JM, Chopra JS, Gulati DR. Subdural hematoma in an adult following a blast injury. Case report. J Neurosurg 1979; 50 (2) 260-261
    CrossrefPubMedGoogle Scholar
  • 25 Taber KH, Warden DL, Hurley RA. Blast-related traumatic brain injury: what is known?. J Neuropsychiatry Clin Neurosci 2006; 18 (2) 141-145
    CrossrefPubMedGoogle Scholar
  • 26 Taber KH, Hurley RA. Update on mild traumatic brain injury: neuropathology and structural imaging. J Neuropsychiatry Clin Neurosci 2013; 25 (1) 1-5
    CrossrefPubMedGoogle Scholar
  • 27 Hetherington HP, Bandak A, Ling G, Bandak F. Advances in imaging explosive blast mild traumatic brain injury. In: Grafman J, Salazar AM, , eds. Handbook of Clinical Neurology. Netherlands: Elsevier; 2015. : In press
    CrossrefGoogle Scholar
  • 28 Davenport ND, Lim KO, Armstrong MT, Sponheim SR. Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury. Neuroimage 2012; 59 (3) 2017-2024
    CrossrefPubMedGoogle Scholar
  • 29 Mac Donald CL, Johnson AM, Cooper D , et al. Detection of blast-related traumatic brain injury in U.S. military personnel. N Engl J Med 2011; 364 (22) 2091-2100
    CrossrefPubMedGoogle Scholar
  • 30 Morey RA, Haswell CC, Selgrade ES , et al. Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans. Hum Brain Mapp 2013; 34 (11) 2986-2999
    CrossrefPubMedGoogle Scholar
  • 31 Peskind ER, Petrie EC, Cross DJ , et al. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms. Neuroimage 2011; 54 (Suppl. 01) S76-S82
    CrossrefPubMedGoogle Scholar
  • 32 de Lanerolle NC, Bandak F, Kang D , et al. Characteristics of an explosive blast-induced brain injury in an experimental model. J Neuropathol Exp Neurol 2011; 70 (11) 1046-1057
    CrossrefPubMedGoogle Scholar
  • 33 Maxwell WL, MacKinnon M-A, Stewart JE, Graham DI. Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow outcome score. Brain 2010; 133 (Pt 1) 139-160
    CrossrefPubMedGoogle Scholar
  • 34 Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 1993; 13 (3) 981-989
    PubMedGoogle Scholar
  • 35 Brooks WM, Friedman SD, Gasparovic C. Magnetic resonance spectroscopy in traumatic brain injury. J Head Trauma Rehabil 2001; 16 (2) 149-164
    CrossrefPubMedGoogle Scholar
  • 36 de Lanerolle NC, Hamid H, Kulas J , et al. Concussive brain injury from explosive blast. Ann Clin Transl Neurol 2014; 1 (9) 692-702
    CrossrefPubMedGoogle Scholar
  • 37 Hetherington HP, Hamid H, Kulas J , et al. MRSI of the medial temporal lobe at 7T in explosive blast mild traumatic brain injury. Magn Reson Med 2014; 71: 1358-1367 10.1002/mrm.24814
    CrossrefPubMedGoogle Scholar
  • 38 Smith C, Gentleman SM, Leclercq PD , et al. The neuroinflammatory response in humans after traumatic brain injury. Neuropathol Appl Neurobiol 2013; 39 (6) 654-666
    CrossrefPubMedGoogle Scholar
  • 39 Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics 2010; 7 (4) 366-377
    CrossrefPubMedGoogle Scholar
  • 40 Aguzzi A, Barres BA, Bennett ML. Microglia: scapegoat, saboteur, or something else?. Science 2013; 339 (6116) 156-161
    CrossrefPubMedGoogle Scholar
  • 41 Garman RH, Jenkins LW, Switzer III RCI , et al. Blast exposure in rats with body shielding is characterized primarily by diffuse axonal injury. J Neurotrauma 2011; 28 (6) 947-959
    CrossrefPubMedGoogle Scholar
  • 42 Kernie SG, Erwin TM, Parada LF. Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 2001; 66 (3) 317-326
    CrossrefPubMedGoogle Scholar
  • 43 Armonda RA, Bell RS, Vo AH , et al. Wartime traumatic cerebral vasospasm: recent review of combat casualties. Neurosurgery 2006; 59 (6) 1215-1225 , discussion 1225
    PubMedGoogle Scholar
  • 44 Ling G, Bandak F, Armonda R, Grant G, Ecklund J. Explosive blast neurotrauma. J Neurotrauma 2009; 26 (6) 815-825
    CrossrefPubMedGoogle Scholar
  • 45 Graham DI, Ford I, Adams JH , et al. Ischaemic brain damage is still common in fatal non-missile head injury. J Neurol Neurosurg Psychiatry 1989; 52 (3) 346-350
    CrossrefPubMedGoogle Scholar
  • 46 Blissitt PA. Care of the critically ill patient with penetrating head injury. Crit Care Nurs Clin North Am 2006; 18 (3) 321-332
    CrossrefPubMedGoogle Scholar
  • 47 Bigler ED, Maxwell WL. Neuropathology of mild traumatic brain injury: relationship to neuroimaging findings. Brain Imaging Behav 2012; 6 (2) 108-136
    CrossrefPubMedGoogle Scholar
  • 48 Iverson GL, Lovell MR, Smith S, Franzen MD. Prevalence of abnormal CT-scans following mild head injury. Brain Inj 2000; 14 (12) 1057-1061
    CrossrefPubMedGoogle Scholar
  • 49 Smits M, Hunink MG, van Rijssel DA , et al. Outcome after complicated minor head injury. AJNR Am J Neuroradiol 2008; 29 (3) 506-513
    CrossrefPubMedGoogle Scholar
  • 50 Orrison WW, Hanson EH, Alamo T , et al. Traumatic brain injury: a review and high-field MRI findings in 100 unarmed combatants using a literature-based checklist approach. J Neurotrauma 2009; 26 (5) 689-701
    CrossrefPubMedGoogle Scholar
  • 51 Maxwell WL, Whitfield PC, Suzen B , et al. The cerebrovascular response to experimental lateral head acceleration. Acta Neuropathol 1992; 84 (3) 289-296
    PubMedGoogle Scholar
  • 52 Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 2003; 74 (7) 857-862
    CrossrefPubMedGoogle Scholar
  • 53 Guo Z, Cupples LA, Kurz A , et al. Head injury and the risk of AD in the MIRAGE study. Neurology 2000; 54 (6) 1316-1323
    CrossrefPubMedGoogle Scholar
  • 54 Plassman BL, Havlik RJ, Steffens DC , et al. Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 2000; 55 (8) 1158-1166
    CrossrefPubMedGoogle Scholar
  • 55 Miller G. Neuropathology. Blast injuries linked to neurodegeneration in veterans. Science 2012; 336 (6083) 790-791
    CrossrefPubMedGoogle Scholar
  • 56 Lakis N, Corona RJ, Toshkezi G, Chin LS. Chronic traumatic encephalopathy - neuropathology in athletes and war veterans. Neurol Res 2013; 35 (3) 290-299
    CrossrefPubMedGoogle Scholar
  • 57 McKee AC, Cantu RC, Nowinski CJ , et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009; 68 (7) 709-735
    CrossrefPubMedGoogle Scholar
  • 58 Schmidt ML, Zhukareva V, Newell KL, Lee VM, Trojanowski JQ. Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease. Acta Neuropathol 2001; 101 (5) 518-524
    CrossrefPubMedGoogle Scholar
  • 59 Hof PR, Delacourte A, Bouras C. Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. Acta Neuropathol 1992; 84 (1) 45-51
    CrossrefPubMedGoogle Scholar
  • 60 Goldstein LE, Fisher AM, Tagge CA , et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 2012; 4 (134) 134ra60
    CrossrefPubMedGoogle Scholar
  • 61 Tsao JW. Comment on “chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model”. Sci Transl Med 2012; 4 (157) 157le7 , author reply 157lr5
    PubMedGoogle Scholar
  • 62 Campbell GA. The pathology of penetrating wounds of the brain and its enclosures. In: Aarabi B, Kaufman HH, , eds. Missile wounds of the head and neck. Park Ridge, IL: American Association of Neurological Surgeons; 1999: 73-89
    Google Scholar
  • 63 Ahmed F, Gyorgy A, Kamnaksh A , et al. Time-dependent changes of protein biomarker levels in the cerebrospinal fluid after blast traumatic brain injury. Electrophoresis 2012; 33 (24) 3705-3711
    CrossrefPubMedGoogle Scholar