Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-s22k5 Total loading time: 0 Render date: 2025-01-14T13:50:25.010Z Has data issue: false hasContentIssue false

Chapter 2 - The Neuropathology of Traumatic Brain Injury

Published online by Cambridge University Press:  28 April 2020

By
David Hilton
Edited by
Peter C. Whitfield ,
Jessie Welbourne ,
Elfyn Thomas ,
Fiona Summers ,
Maggie Whyte  and
Peter J. Hutchinson
Peter C. Whitfield
Affiliation:
Derriford Hospital, Plymouth
Jessie Welbourne
Affiliation:
University Hospitals, Plymouth
Elfyn Thomas
Affiliation:
Derriford Hospital, Plymouth
Fiona Summers
Affiliation:
Aberdeen Royal Infirmary
Maggie Whyte
Affiliation:
Aberdeen Royal Infirmary
Peter J. Hutchinson
Affiliation:
Addenbrooke’s Hospital, Cambridge
Get access

Summary

The neuropathological changes associated with head injuries are dependent on a number of factors, including both the type and severity of the injury, and the former can be divided into non-missile and missile types of injury. Non-missile injury (or blunt head injury) is usually due to rapid acceleration or deceleration of the head, with or without impact, or less commonly crushing of the head, and most often occur as the result of road traffic accidents or falls. Missile injuries are due to penetration of the skull by a rapidly moving external object, for example gunshot wounds, and result in a different pattern of brain injury. The neuropathology can be separated into focal (or localised) lesions such as contusions, haemorrhages, skull fractures, or diffuse changes such as diffuse axonal injury, diffuse vascular injury, brain swelling and ischaemia (see Table 2.1).

Type
Chapter
Information
Traumatic Brain Injury
A Multidisciplinary Approach
 , pp. 12 - 23
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Tien, HC, Tremblay, LN, Rizoli, SB, Gelberg, J, Chughtai, T, Tikuisis, P, et al. Association between alcohol and mortality in patients with severe traumatic head injury. Arch Surg 2006;141:1185–91.Google Scholar
Smith, C, Graham, DI, Murray, LS, Stewart, J, Nicoll, JA. Association of APOE e4 and cerebrovascular pathology in traumatic brain injury. J Neurol Neurosurg Psychiatry 2006;77:363–6.Google ScholarPubMed
Sorbi, S, Nacmias, B, Piacentini, S, Repice, A, Latorraca, S, Forleo, P, et al. ApoE as a prognostic factor for post-traumatic coma. Nat Med 1995;1:852.Google Scholar
Servadei, F, Ciucci, G, Morichetti, A, Pagano, F, Burzi, M, Staffa, G, et al. Skull fracture as a factor of increased risk in minor head injuries: indication for a broader use of cerebral computed tomography scanning. Surg Neurol 1988;30:364–9.CrossRefGoogle ScholarPubMed
Mendelow, AD, Teasdale, G, Jennett, B, Bryden, J, Hessett, C, Murray, G. Risks of intracranial haematoma in head injured adults. Br Med J (Clin Res Ed) 1983;287:1173–6.Google ScholarPubMed
Rivas, JJ, Lobato, RD, Sarabia, R, Cordobes, F, Cabrera, A, Gomez, P. Extradural hematoma: analysis of factors influencing the courses of 161 patients. Neurosurgery 1988;23:44–51.Google Scholar
Tokoro, K, Nakajima, F, Yamataki, A. Acute spontaneous subdural hematoma of arterial origin. Surg Neurol 1988;29:159–63.Google Scholar
Yamashima, T, Yamamoto, S. How do vessels proliferate in the capsule of a chronic subdural hematoma? Neurosurgery 1984;15:672–8.Google Scholar
Domenicucci, M, Signorini, P, Strzelecki, J, Delfini, R. Delayed post-traumatic epidural hematoma: a review. Neurosurg Rev 1995;18:109–22.Google Scholar
Coast, GC, Gee, DJ. Traumatic subarachnoid haemorrhage: an alternative source. J Clin Pathol 1984;37:1245–8.Google Scholar
Dolman, CL. Rupture of posterior inferior cerebellar artery by single blow to head. Arch Pathol Lab Med 1986;110:494–6.Google Scholar
Fujitsu, K, Kuwabara, T, Muramoto, M, Hirata, K, Mochimatsu, Y. Traumatic intraventricular hemorrhage: report of twenty-six cases and consideration of the pathogenic mechanism. Neurosurgery 1988;23:423–30.Google Scholar
Dolinak, D, Smith, C, Graham, DI. Global hypoxia per se is an unusual cause of axonal injury. Acta Neuropathol (Berl) 2000;100:553–60.Google Scholar
Dolinak, D, Smith, C, Graham, DI. Hypoglycaemia is a cause of axonal injury. Neuropathol Appl Neurobiol 2000;26:448–53.Google Scholar
Reichard, RR, Smith, C, Graham, DI. The significance of beta-APP immunoreactivity in forensic practice. Neuropathol Appl Neurobiol 2005;31:304–13.CrossRefGoogle ScholarPubMed
Gennarelli, TA, Thibault, LE, Adams, JH, Graham, DI, Thompson, CJ, Marcincin, RP. Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 1982;12:564–74.CrossRefGoogle ScholarPubMed
Graham, DI, Clark, JC, Adams, JH, Gennarelli, TA. Diffuse axonal injury caused by assault. J Clin Pathol 1992;45:840–1.Google Scholar
Pilz, P. Axonal injury in head injury. Acta Neurochir Suppl (Wien) 1983;32:119–23.Google Scholar
Adams, JH, Doyle, D, Ford, I, Gennarelli, TA, Graham, DI, McLellan, DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 1989;15:49–59.CrossRefGoogle ScholarPubMed
Strich, SJ. Diffuse degeneration of the cerebral white matter in severe dementia following head injury. J Neurol Neurosurg Psychiatry 1956;19:163–85.CrossRefGoogle ScholarPubMed
Hortobagyi, T, Wise, S, Hunt, N, Cary, N, Djurovic, V, Fegan-Earl, A, 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;33:226–37.CrossRefGoogle ScholarPubMed
Johnson, GV, Litersky, JM, Jope, RS. Degradation of microtubule-associated protein 2 and brain spectrin by calpain: a comparative study. J Neurochem 1991;56:1630–8.Google Scholar
Kampfl, A, Posmantur, R, Nixon, R, Grynspan, F, Zhao, X, Liu, SJ, et al. Mu-calpain activation and calpain-mediated cytoskeletal proteolysis following traumatic brain injury. J Neurochem 1996;67:1575–83.Google Scholar
Povlishock, JT. Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol 1992;2:1–12.Google Scholar
Maxwell, WL, Graham, DI. Loss of axonal microtubules and neurofilaments after stretch-injury to guinea pig optic nerve fibers. J Neurotrauma 1997;14:603–14.Google Scholar
Graham, DI, Ford, I, Adams, JH, Doyle, D, Lawrence, AE, McLellan, DR, et al. Fatal head injury in children. J Clin Pathol 1989;42:18–22.Google Scholar
Bouma, GJ, Muizelaar, JP, Fatouros, P. Pathogenesis of traumatic brain swelling: role of cerebral blood volume. Acta Neurochir Suppl 1998;71:272–5.Google Scholar
Geddes, JF, Hackshaw, AK, Vowles, GH, Nickols, CD, Whitwell, HL. Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Brain 2001;124:1290–8.Google Scholar
Geddes, JF, Tasker, RC, Hackshaw, AK, Nickols, CD, Adams, GG, Whitwell, HL, et al. Dural haemorrhage in non-traumatic infant deaths: does it explain the bleeding in ‘shaken baby syndrome’? Neuropathol Appl Neurobiol 2003;29:14–22.Google Scholar
Reece, RM. The evidence base for shaken baby syndrome: response to editorial from 106 doctors. BMJ 2004;328:1316–7.Google Scholar
Smith, DH, Chen, XH, Pierce, JE, 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.Google Scholar
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;7:857–62.Google Scholar
Maroon, JC, Winkelman, R, Bost, J, Amos, A, Mathyssek, C, Miele, V. Chronic traumatic encephalopathy in contact sports: a systematic review of all reported pathological cases. PloS ONE 2015;10:e0117338.Google Scholar
Roberts, GW, Gentleman, SM, Lynch, A, Graham, DI. Beta A4 amyloid protein deposition in brain after head trauma. Lancet 1991;338:1422–3.Google Scholar
Nicoll, JA, Roberts, GW, Graham, DI. Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1995;1:135–7.Google Scholar
Geddes, JF, Vowles, GH, Robinson, SF, Sutcliffe, JC. Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 1996;22:12–16.CrossRefGoogle ScholarPubMed
Nilsson, P, Hillered, L, Ponten, U, Ungerstedt, U. Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 1990;10:631–7.Google Scholar
Zhang, H, Zhang, X, Zhang, T, Chen, L. Excitatory amino acids in cerebrospinal fluid of patients with acute head injuries. Clin Chem 2001;47:1458–62.Google ScholarPubMed
Fineman, I, Hovda, DA, Smith, M, Yoshino, A, Becker, DP. Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Res 1993;624:94–102.CrossRefGoogle ScholarPubMed
Olney, JW, Rhee, V, Ho, OL. Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 1974;77:507–12.Google Scholar
Olney, JW, Ho, OL, Rhee, V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res 1971;14:61–76.Google Scholar
Ikonomidou, C, Mosinger, JL, Salles, KS, Labruyere, J, Olney, JW. Sensitivity of the developing rat brain to hypobaric/ischaemic damage parallels sensitivity to N-methyl-aspartate neurotoxicity. J Neurosci 1989;8:2809–18.Google Scholar
Shohami, E, Shapira, Y, Yadid, G, Reisfeld, N, Yedgar, S. Brain phospholipase A2 is activated after experimental closed head injury in the rat. J Neurochem 1989;53:1541–6.CrossRefGoogle ScholarPubMed
Dhillon, HS, Donaldson, D, Dempsey, RJ, Prasad, MR. Regional levels of free fatty acids and Evans blue extravasation after experimental brain injury. J Neurotrauma 1994;11:405–15.Google Scholar
Dugan, LL, Choi, DW. Excitotoxicity, free radicals, and cell membrane changes. Ann Neurol 1994;35 Suppl:S17–S21.Google Scholar
Fee, D, Crumbaugh, A, Jacques, T, Herdrich, B, Sewell, D, Auerbach, D, et al. Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J Neuroimmunol 2003;136:54–66.Google Scholar
Feuerstein, GZ, Wang, X, Barone, FC. Inflammatory gene expression in cerebral ischemia and trauma: potential new therapeutic targets. Ann N Y Acad Sci 1997;825:179–93.Google Scholar
Bruce, AJ, Boling, W, Kindy, MS, Peschon, J, Kraemer, PJ, Carpenter, MK, et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 1996;2:788–94.Google Scholar
Cheng, B, Christakos, S, Mattson, MP. Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis. Neuron 1994;12:139–53.CrossRefGoogle ScholarPubMed
DeKosky, ST, Styren, SD, O’Malley, ME, Goss, JR, Kochanek, P, Marion, D, et al. Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain. Ann Neurol 1996;39:123–7.Google Scholar
Mattson, MP, Goodman, Y, Luo, H, Fu, W, Furukawa, K. Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J Neurosci Res 1997;49:681–97.Google Scholar
Griffin, WS, Sheng, JG, Royston, MC, Gentleman, SM, McKenzie, JE, Graham, DI, et al. Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 1998;1:65–72.CrossRefGoogle Scholar
Huang, Z, Huang, PL, Ma, J, Meng, W, Ayata, C, Fishman, MC, et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab 1996;16:981–7.Google Scholar
Dewitt, DS, Smith, TG, Deyo, DJ, Miller, KR, Uchida, T, Prough, DS. L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury. J Neurotrauma 1997;14:223–33.Google Scholar
Schulz, JB, Matthews, RT, Jenkins, BG, Ferrante, RJ, Siwek, D, Henshaw, DR, et al. Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo. J Neurosci 1995;15:8419–29.Google Scholar
Sinz, EH, Kochanek, PM, Dixon, CE, Clark, RS, Carcillo, JA, Schiding, JK, et al. Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice. J Clin Invest 1999;104:647–56.Google Scholar
Lipton, SA, Choi, YB, Pan, ZH, Lei, SZ, Chen, HS, Sucher, NJ, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 1993;364:626–32.Google Scholar
Beckman, JS, Beckman, TW, Chen, J, Marshall, PA, Freeman, BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 1990;87(4):1620–4.Google Scholar
Kim, YM, Talanian, RV, Billiar, TR. Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms. J Biol Chem 1997;272:31138–48.Google Scholar
Garry, PS, Ezra, M, Rowland, MJ, Westbrook, J, Pattinson, KTS. The role of nitric oxide pathway in brain injury and its treatment – from bench to bedside. Exp Neurol 2015;263:235–43.Google Scholar
Newcomb, JK, Zhao, X, Pike, BR, Hayes, RL. Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat. Exp Neurol 1999;158:76–88.Google Scholar
Nakamura, M, Raghupathi, R, Merry, DE, Scherbel, U, Saatman, KE, McIntosh, TK. Overexpression of Bcl-2 is neuroprotective after experimental brain injury in transgenic mice. J Comp Neurol 1999;412:681–92.Google Scholar
Eldadah, BA, Faden, AI. Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma 2000;17:811–29.Google Scholar
Aikman, J, O’Steen, B, Silver, X, Torres, R, Boslaugh, S, Blackband, S, et al. Alpha-II-spectrin after controlled cortical impact in the immature rat brain. Dev Neurosci 2006;28:457–65.Google Scholar
Liu, X, Zou, H, Slaughter, C, Wang, X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 1997;89:175–84.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×