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. 2006 Apr 5;14(2):185–194. doi: 10.1111/j.1750-3639.2004.tb00052.x

Moderate and Severe Traumatic Brain Injury: Epidemiologic, Imaging and Neuropathologic Perspectives

David L McArthur 1,✉, Dennis J Chute 2, J Pablo Villablanca 3
PMCID: PMC8095962  PMID: 15193031

Abstract

This article examines 3 contexts in which moderate or severe traumatic brain injury can be approached. The epidemiologic background of moderate and severe traumatic brain injury is presented, with particular attention paid to new findings from the study of a national hospital inpatient database. We review aspects of neuroimaging and how new imaging modalities can reveal fine detail about traumatic brain injury. Finally we examine the current state of neuropathologic evaluation of, and recent developments in, understanding of the neural disruptions that occur following traumatic brain injury, together with cellular reactions to these disruptions.

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REFERENCES

  • 1. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR (1989) Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15:49–59. [DOI] [PubMed] [Google Scholar]
  • 2. Adekoya N, Thurman DJ, White DD, Webb KW (2002) Surveillance for traumatic brain injury deaths‐United States, 1989–1998. MMWR Surveill Summ 51:1–14. [PubMed] [Google Scholar]
  • 3. Alessandri B, Rice AC, Levasseur J, DeFord M, Hamm RJ, Bullock MR (2002) Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats. J Neurotrauma 19: 829–841. [DOI] [PubMed] [Google Scholar]
  • 4. American Academy of Pediatrics : Committee on Child Abuse and Neglect. (2001) Shaken baby syndrome: rotational cranial injuries‐technical report. Pediatrics 108:206–210. [DOI] [PubMed] [Google Scholar]
  • 5. Andersson EH, Björklund R, Emanuelson I, Stålhammar D (2003) Epidemiology of traumatic brain injury: a population based study in western Sweden. Acta Neurologica Scand 107:256–259. [DOI] [PubMed] [Google Scholar]
  • 6. Arias E, Anderson RN, Kung H‐C, Murphy SL, Kochanek KD (2003) Deaths: final data for 2001. National Vital Statistics Reports V. 52, no. 3. Hyattsville , MD : National Center for Health Statistics. [PubMed] [Google Scholar]
  • 7. Bain AC, Raghupathi R, Meaney DF (2001) Dynamic stretch correlates to both morphological abnormalities and electrophysiological impairment in a model of traumatic axonal injury. J Neurotrauma 18:499–511. [DOI] [PubMed] [Google Scholar]
  • 8. Bigler ED, Blatter DD, Johnson SC, Anderson CV, Russo AA, Gale SD, Ryser DK, MacNamara SE, Bailey BJ (1996) Traumatic brain injury, alcohol and quantitative neuroimaging: preliminary findings. Brain Inj 10:197–206. [DOI] [PubMed] [Google Scholar]
  • 9. Black IB, Woodbury D (2001) Adult rat and human bone marrow stromal stem cells differentiate into neurons. Blood Cells Mol Dis 27:632–636. [DOI] [PubMed] [Google Scholar]
  • 10. Black M, Graham DI (2002) Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol 55:44–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ (1994) Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344:1055–1056. [DOI] [PubMed] [Google Scholar]
  • 12. Buki A, Okonkwo DO, Wang KK, Povlishock JT (2000) Cytochrome c release and caspase activation in traumatic axonal injury. J Neurosci 20:2825–2834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Bureau of Injury Prevention (1997) Injury facts for New York state, Albany , NY , New York State Department of Health. [Google Scholar]
  • 14. Butler TL, Kassed CA, Pennypacker KR (2003) Signal transduction and neurosurvival in experimental models of brain injury. Brain Res Bull 59: 339–351. [DOI] [PubMed] [Google Scholar]
  • 15. Cameron HA, McKay R (1998) Stem cells and neurogenesis in the adult brain. Curr Opin Neurobiol 8:677–680. [DOI] [PubMed] [Google Scholar]
  • 16. Cao Q, Benton RL, Whittemore SR (2002) Stem cell repair of central nervous system injury. J Neurosci Res 68:501–510. [DOI] [PubMed] [Google Scholar]
  • 17. Chen S, Pickard JD, Harris NG (2003) Time course of cellular pathology after controlled cortical impact injury. Exp Neurol 182:87–102. [DOI] [PubMed] [Google Scholar]
  • 18. Chen XH, Iwata A, Nonaka M, Browne KD, Smith DH (2003) Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in rats. J Neurotrauma 20:623–631. [DOI] [PubMed] [Google Scholar]
  • 19. Chung RS, Vickers JC, Chuah MI, West AK (2003) Metallothionein‐IIA promotes initial neurite elongation and postinjury reactive neurite growth and facilitates healing after focal cortical brain injury. J Neurosci 23:3336–3342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Cihangirolu M, Ramsey RG, Dohrmann GJ (2002) Brain injury: Analysis of imaging modalities. Neurol Res 24:7–18. [DOI] [PubMed] [Google Scholar]
  • 21. Conti AC, Raghupathi R, Trojanowski JQ, McIntosh TK (1998) Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post‐traumatic period. J Neurosci 18:5663–5672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Contostavlos DL (1995) Isolated basilar traumatic subarachnoid hemorrhage: an observer's 25 year re‐evaluation of the pathogenetic possibilities. Forensic Sci Int 73:61–74. [DOI] [PubMed] [Google Scholar]
  • 23. Cory CZ, Jones BM (2003) Can shaking alone cause fatal brain injury? A biomechanical assessment of the Duhaime shaken baby syndrome model. Med Sci Law 43:317–333. [DOI] [PubMed] [Google Scholar]
  • 24. Denslow N, Michel ME, Temple MD, Hsu CY, Saatman K, Hayes RL (2003) Application of proteomics technology to the field of neurotrauma. J Neurotrauma 20:401–407. [DOI] [PubMed] [Google Scholar]
  • 25. DeWitt DS, Prough DS (2003) Traumatic cerebral vascular injury: the effects of concussive brain injury on the cerebral vasculature. J Neurotrauma 20:795–825. [DOI] [PubMed] [Google Scholar]
  • 26. Durkin MS, Olsen S, Barlow B, Virella A, Connolly ES Jr (1998) The epidemiology of urban pediatric neurological trauma: evaluation of, and implications for, injury prevention programs. Neurosurgery 42:300–310. [DOI] [PubMed] [Google Scholar]
  • 27. Engberg AW, Teasdale TW (2001) Traumatic brain injury in Denmark 1979–1996. A national study of incidence and mortality. Eur J Epidemiology 17:437–42. [DOI] [PubMed] [Google Scholar]
  • 28. Erb DE, Povlishock JT (1988) Axonal damage in severe traumatic brain injury: an experimental study in cat. Acta Neuropathol (Berl) 76:347–358. [DOI] [PubMed] [Google Scholar]
  • 29. Fee D, Crumbaugh A, Jacques T, Herdrich B, Sewell D, Auerbach D, Piaskowski S, Hart MN, Sandor M, Fabry Z (2003) Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J Neuroimmunol 136:54–66. [DOI] [PubMed] [Google Scholar]
  • 30. Gaetz M (2004) The neurophysiology of brain injury. Clin Neurophysiol 115:4–18. [DOI] [PubMed] [Google Scholar]
  • 31. Gean AD (1994) Imaging of head trauma. New York , Raven Press. [Google Scholar]
  • 32. Geddes JF, Vowles GH, Beer TW, Ellison DW (1997) The diagnosis of diffuse axonal injury: implications for forensic practice. Neuropathol Appl Neurobiol 23:339–347. [PubMed] [Google Scholar]
  • 33. Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW (1993. Beta‐amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 160:139–144. [DOI] [PubMed] [Google Scholar]
  • 34. Giza CC, Prins ML, Hovda DA, Herschman HR, Feldman JD (2002) Genes preferentially induced by depolarization after concussive brain injury: effects of age and injury severity. J Neurotrauma 19:387–402. [DOI] [PubMed] [Google Scholar]
  • 35. Golding EM (2002) Sequelae following traumatic brain injury. The cerebrovascular perspective. Brain Res Brain Res Rev 38:377–388. [DOI] [PubMed] [Google Scholar]
  • 36. Gómez PA, Lobato RD, De la Boto GR, Lama A, González PJ, de la Cruz J (2000) Age and outcome after severe head injury. Acta Neurochir (Wien) 142:373–381. [DOI] [PubMed] [Google Scholar]
  • 37. Graham DI, Adams JH, Nicoll JA, Maxwell WL, Gennarelli TA (1995) The nature, distribution and causes of traumatic brain injury. Brain Pathol 5: 397–406. [DOI] [PubMed] [Google Scholar]
  • 38. Graham DI, Gennarelli TA, McIntosh TK (2003) Trauma. In Graham DI, Lantos PL (eds), Greenfield's Neuropathology. 7th ed. New York , Oxford University Press, p 848. [Google Scholar]
  • 39. Guerrero DL, Thurman DJ, Sniezek JE (2000) Emergency department visits associated with traumatic brain injury: United States, 1995–1996. Brain Injury 14:181–186. [PubMed] [Google Scholar]
  • 40. Hamberger A, Huang YL, Zhu H, Bao F, Ding M, Blennow K, Olsson A, Hansson HA, Viano D, Haglid KG (2003) Redistribution of neurofilaments and accumulation of beta‐amyloid protein after brain injury by rotational acceleration of the head. J Neurotrauma 20:169–178. [DOI] [PubMed] [Google Scholar]
  • 41. Higashi K, Sakata Y, Hatano M, Abiko S, Ihara K, Katayama S, Wakuta Y, Okamura T, Ueda H, Zenke M, Aoki H (1977) Epidemiological studies on patients with a persistent vegetative state. J Neurol Neurosurg Psychiat 40:876–885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Hlatky R, Goodman JC, Valadka AB, Robertson CS (2003) Role of nitric oxide in cerebral blood flow abnormalities after traumatic brain injury. J Cereb Blood Flow Metab 23:582–588. [DOI] [PubMed] [Google Scholar]
  • 43. Hortobagyi T, Gorlach C, Benyo Z, Lacza Z, Hortobagyi S, Wahl M, Harkany T (2003) Inhibition of neuronal nitric oxide synthase‐mediated activation of poly(ADP‐ribose) polymerase in traumatic brain injury: neuroprotection by 3‐aminobenzamide. Neuroscience 121:983–990. [DOI] [PubMed] [Google Scholar]
  • 44. Howsepian AA (1996) The 1994 Multi‐Society Task Force consensus statement on the Persistent Vegetative State: a critical analysis. Issues Law Med 12:3–29. [PubMed] [Google Scholar]
  • 45. Hukkelhoven CWPM, Steyerberg EW, Rampen AJJ, Farace E, Habbema JDF, Marshall LF, Murray GD, Maas AIR (2003) Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients. J Neurosurg 99:666–673. [DOI] [PubMed] [Google Scholar]
  • 46. International Classification of Diseases 9th Revision, Clinical Modification (2001) US Department of Health and Human Services. Washington , US Government Printing Office. [Google Scholar]
  • 47. Ishibashi A, Yokokura Y (1991) Clinical analysis of traumatic subarachnoid hemorrhage. Kurume Med J 38:167–171. [DOI] [PubMed] [Google Scholar]
  • 48. Ivarsson J, Viano DC, Lovsund P, Aldman B (2000) Strain relief from the cerebral ventricles during head impact: experimental studies on natural protection of the brain. J Biomech 33: 181–189. [DOI] [PubMed] [Google Scholar]
  • 49. Jafari SS, Maxwell WL, Neilson M, Graham DI (1997) Axonal cytoskeletal changes after non‐disruptive axonal injury. J Neurocytol 26: 207–221. [DOI] [PubMed] [Google Scholar]
  • 50. Jafari SS, Nielson M, Graham DI, Maxwell WL (1998) Axonal cytoskeletal changes after non‐disruptive axonal injury. II. Intermediate sized axons. J Neurotrauma 15:955–966. [DOI] [PubMed] [Google Scholar]
  • 51. Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1: 480–484. [DOI] [PubMed] [Google Scholar]
  • 52. Kampfl A, Schmutzhard E, Franz G, Pfausler B, Haring HP, Ulmer H, Felber S, Golaszewski S, Aichner F (1998) Prediction of recovery from post‐traumatic vegetative state with cerebral magnetic‐resonance imaging. Lancet 351:1763–1767. [DOI] [PubMed] [Google Scholar]
  • 53. Kaur B, Rutty GN, Timperley WR (1999) The possible role of hypoxia in the formation of axonal bulbs. J Clin Pathol 52:203–209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54. Keyvani K, Schallert T (2002) Plasticity‐associated molecular and structural events in the injured brain. J Neuropathol Exp Neurol 61: 831–840. [DOI] [PubMed] [Google Scholar]
  • 55. Kraus JF, McArthur DL (2003) Brain and spinal cord injury. In Nelson LM, Tanner CM, Van Den Ederen S, McGuire V (eds), Neuroepidemiology, from principles to practice. New York , Oxford University Press, pp. 254–277. [Google Scholar]
  • 56. Kraus JF, McArthur DL (1996) Epidemiology of brain injury. In Evans RW (ed), Neurology and trauma. Philadelphia , WB Saunders, pp. 3–17. [Google Scholar]
  • 57. Lambri M, Djurovic V, Kibble M, Cairns N, AlSarraj S (2001) Specificity and sensitivity of betaAPP in head injury. Clin Neuropathol 20:263–271. [PubMed] [Google Scholar]
  • 58. Leker RR, Shohami E (2002) Cerebral ischemia and trauma‐different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev 39:55–73. [DOI] [PubMed] [Google Scholar]
  • 59. Levin HS, Saydjari C, Eisenberg HM, Foulkes M, Marshall LF, Ruff RM, Jane JA, Marmarou A (1991). Vegetative state after closed‐head injury. A Traumatic Coma Data Bank Report. Arch Neurol 48:580–585. [DOI] [PubMed] [Google Scholar]
  • 60. Liang L, Korogi Y, Sugahara T, Shigematsu Y, Okuda T, Ikushima I, Takahashi M (1999) Detection of intracranial hemorrhage with susceptibility‐weighted MR sequences. AJNR Amer J Neuroradiol 20:1527–1534. [PMC free article] [PubMed] [Google Scholar]
  • 61. Lifshitz J, Friberg H, Neumar RW, Raghupathi R, Welsh FA, Janmey P, Saatman KE, Wieloch T, Grady MS, McIntosh TK (2003) Structural and functional damage sustained by mitochondria after traumatic brain injury in the rat: evidence for differentially sensitive populations in the cortex and hippocampus. J Cereb Blood Flow Metab 23:219–231. [DOI] [PubMed] [Google Scholar]
  • 62. Liou AK, Clark RS, Henshall DC, Yin XM, Chen J (2003) To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: a review on the stress‐activated signaling pathways and apoptotic pathways. Prog Neurobiol 69:103–142. [DOI] [PubMed] [Google Scholar]
  • 63. Liu AY, Maldjian JA, Bagley LJ, Sinson GP, Grossman RI. (1999) Traumatic brain injury: diffusion‐weighted MR imaging findings. AJNR Amer J Neuroradiol 20:1636–1641. [PMC free article] [PubMed] [Google Scholar]
  • 64. Long Y, Zou L, Liu H, Lu H, Yuan X, Robertson CS, Yang K (2003) Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury. J Neurosci Res 71:710–720. [DOI] [PubMed] [Google Scholar]
  • 65. Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L (2001) Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 2001 136:1118–1123. [DOI] [PubMed] [Google Scholar]
  • 66. Masson F, Thicoipe M, Aye P, Mokni T, Senjean P, Schmitt V, Dessalles P‐H, Cazaugade M, Labadens P, and The Aquitaine Group for Severe Brain Injuries Study (2001) Epidemiology of severe brain injuries: a prospective population‐based study. J Trauma 51:481–489. [DOI] [PubMed] [Google Scholar]
  • 67. Mattioli C, Beretta L, Gerevini S, Veglia F, Citerio G, Cormio M, Stocchetti N (2003) Traumatic subarachnoid hemorrhage on the computerized tomography scan obtained at admission: a multicenter assessment of the accuracy of diagnosis and the potential impact on patient outcome. J Neurosurg 98:37–42. [DOI] [PubMed] [Google Scholar]
  • 68. Matzilevich DA, Rall JM, Moore AN, Grill RJ, Dash PK (2002) High‐density microarray analysis of hippocampal gene expression following experimental brain injury. J Neurosci Res 67: 646–663. [DOI] [PubMed] [Google Scholar]
  • 69. Maxwell WL, Domleo A, McColl G, Jafari SS, Graham DI (2003) Post‐acute alterations in the axonal cytoskeleton after traumatic axonal injury. J Neurotrauma 20:151–168. [DOI] [PubMed] [Google Scholar]
  • 70. McCracken E, Hunter AJ, Patel S, Graham DI, Dewar D (1999) Calpain activation and cytoskeletal protein breakdown in the corpus callosum of head‐injured patients. J Neurotrauma 16: 749–761. [DOI] [PubMed] [Google Scholar]
  • 71. McKenzie KJ, McLellan DR, Gentleman SM, Maxwell WL, Gennarelli TA, Graham DI (1996) Is beta‐APP a marker of axonal damage in shortsurviving head injury. Acta Neuropathol (Berl) 92:608–613. [DOI] [PubMed] [Google Scholar]
  • 72. Medana IM, Esiri MM (2003) Axonal damage: a key predictor of outcome in human CNS diseases. Brain 126:515–530. [DOI] [PubMed] [Google Scholar]
  • 73. The Multi‐Society Task Force on PVS (1994) Medical aspects of the persistent vegetative state (1) and (2). N Engl J Med 330:1499–508, 1572–1579. [DOI] [PubMed] [Google Scholar]
  • 74. Niess C, Grauel U, Toennes SW, Bratzke H (2002) Incidence of axonal injury in human brain tissue. Acta Neuropathol 104:79–84. [DOI] [PubMed] [Google Scholar]
  • 75. Oehmichen M, Meissner C, Schmidt V, Pedal I, Konig HG, Saternus KS (1998) Axonal injury‐a diagnostic tool in forensic neuropathology? A review. Forensic Sci Int 95:67–83. [DOI] [PubMed] [Google Scholar]
  • 76. Oertel M, Kelly DF, McArthur D, Boscardin WJ, Glenn TC, Lee JH, Gravori T, Obukhov D, McBride DQ, Martin NA (2002) Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg 96:109–16. [DOI] [PubMed] [Google Scholar]
  • 77. Okonkwo DO, Melon DE, Pellicane AJ, Mutlu LK, Rubin DG, Stone JR, Helm GA (2003) Dose‐response of cyclosporin A in attenuating traumatic axonal injury in rat. Neuroreport 14:463–466. [DOI] [PubMed] [Google Scholar]
  • 78. Okonkwo DO, Pettus EH, Moroi J, Povlishock JT (1998) Alteration of the neurofilament sidearm and its relation to neurofilament compaction occurring with traumatic axonal injury. Brain Res 784:1–6. [DOI] [PubMed] [Google Scholar]
  • 79. Okonkwo DO, Stone JR (2003) Basic science of closed head injuries and spinal cord injuries. Clin Sports Med 22:467–481. [DOI] [PubMed] [Google Scholar]
  • 80. Ommaya AK, Goldsmith W, Thibault L (2002) Biomechanics and neuropathology of adult and paediatric head injury. Br J Neurosurg 16: 220–242. [DOI] [PubMed] [Google Scholar]
  • 81. Onaya M (2002) Neuropathological investigation of cerebral white matter lesions caused by closed head injury. Neuropathology 22:243–251. [DOI] [PubMed] [Google Scholar]
  • 82. Pagni CA, Giovanelli M, Tomei G, Zavanone M, Signoroni G, Cappricci E (1977) Long‐term results in 62 cases of post‐traumatic complete apallic syndrome. Acta Neurochir(Wien) 36:37–45. [DOI] [PubMed] [Google Scholar]
  • 83. Petrov T, Rafols JA (2001) Acute alterations of endothelin‐1 and iNOS expression and control of the brain microcirculation after head trauma. Neurol Res 23:139–143. [DOI] [PubMed] [Google Scholar]
  • 84. Pettus EH, Povlishock JT (1996) Characterization of a distinct set of intra‐axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability. Brain Res 722:1–11. [DOI] [PubMed] [Google Scholar]
  • 85. Philip S, Armstead WM (2003) Differential role of PTK, ERK and p38 MAPK in superoxide impairment of NMDA cerebrovasodilation. Brain Res 979:98–103. [DOI] [PubMed] [Google Scholar]
  • 86. Phillis JW, O'Regan MH (2003) The role of phospholipases, cyclooxygenases, and lipoxygenases in cerebral ischemic/traumatic injuries. Crit Rev Neurobiol 15:61–90. [DOI] [PubMed] [Google Scholar]
  • 87. Pilitsis JG, Coplin WM, O'Regan MH, Wellwood JM, Diaz FG, Fairfax MR, Michael DB, Phillis JW (2003) Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury. Neuro sci Lett 349:136–138. [DOI] [PubMed] [Google Scholar]
  • 88. Pittella JE, Gusmao SN (2003) Diffuse vascular injury in fatal road traffic accident victims: its relationship to diffuse axonal injury. J Forensic Sci 48:626–630. [PubMed] [Google Scholar]
  • 89. Povlishock JT, Becker DP, Cheng CL, Vaughan GW (1983) Axonal change in minor head injury. J Neuropathol Exp Neurol 42:225–242. [DOI] [PubMed] [Google Scholar]
  • 90. Price M, Lang MG, Frank AT, Goetting‐Minesky MP, Patel SP, Silviera ML, Krady JK, Milner RJ, Ewing AG, Day JR (2003) Seven cDNAs enriched following hippocampal lesion: possible roles in neuronal responses to injury. Mol Brain Res 117: 58–67. [DOI] [PubMed] [Google Scholar]
  • 91. Raabe A, Kopetsch O, Woszczyk A, Lang J, Gerlach R, Zimmermann M, Seifert V (2003) Serum S‐100B protein as a molecular marker in severe traumatic brain injury. Restor Neurol Neurosci 21: 159–169. [PubMed] [Google Scholar]
  • 92. Raghavendra Rao VL, Dhodda VK, Song G, Bowen KK, Dempsey RJ (2003) Traumatic brain injury‐induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis. J Neurosci Res 71:208–219. [DOI] [PubMed] [Google Scholar]
  • 93. Raghupathi R, Strauss KI, Zhang C, Krajewski S, Reed JC, McIntosh TK (2003) Temporal alterations in cellular Bax:Bcl‐2 ratio following traumatic brain injury in the rat. J Neurotrauma 20:421–435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94. Rall JM, Matzilevich DA, Dash PK (2003) Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury. Neuropathol Appl Neurobiol 29:118–131. [DOI] [PubMed] [Google Scholar]
  • 95. Roof RL, Duvdevani R, Braswell L, Stein DG (1994) Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Exp Neurol 129:64–69. [DOI] [PubMed] [Google Scholar]
  • 96. Roof RL, Duvdevani R, Heyburn JW, Stein DG (1996) Progesterone rapidly decreases brain edema: treatment delayed up to 24 hours is still effective. Exp Neurol 138:246–251. [DOI] [PubMed] [Google Scholar]
  • 97. Scheff SW, Sullivan PG (1999) Cyclosporin A significantly ameliorates cortical damage following experimental traumatic brain injury in rodents. J Neurotrauma 16:783–792. [DOI] [PubMed] [Google Scholar]
  • 98. Schweitzer JB, Park MR, Einhaus SL, Robertson JT (1993) Ubiquitin marks the reactive swellings of diffuse axonal injury. Acta Neuropathol (Berl) 85:503–507. [DOI] [PubMed] [Google Scholar]
  • 99. Sosin DM, Sniesek JE, Waxweiler RJ (1995) Trends in death associated with traumatic brain injury, 1979 through 1992: success and failure. JAMA 273:1778–1780. [PubMed] [Google Scholar]
  • 100. Steiner C, Elixhauser A, Schnaier J (2002) The healthcare cost and utilization project: an overview. Effective Clinical Practice 5:143–151. [PubMed] [Google Scholar]
  • 101. Stone JR, Singleton RH, Povlishock JT (2000) Antibodies to the C‐terminus of the beta‐amyloid precursor protein (APP): a site specific marker for the detection of traumatic axonal injury. Brain Res 871:288–302. [DOI] [PubMed] [Google Scholar]
  • 102. Stone JR, Singleton RH, Povlishock JT (2001) Intra‐axonal neurofilament compaction does not evoke local axonal swelling in all traumatically injured axons. Exp Neurol 172:320–331. [DOI] [PubMed] [Google Scholar]
  • 103. Stone JR, Walker SA, Povlishock JT (1999) The visualization of a new class of traumatically injured axons through the use of a modified method of microwave antigen retrieval. Acta Neuropathol (Berl) 97:335–345. [DOI] [PubMed] [Google Scholar]
  • 104. Sullivan PG, Thompson MB, Scheff SW (1999) Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury. Exp Neurol 160:226–234. [DOI] [PubMed] [Google Scholar]
  • 105. Tandon PN (2001) Acute subdural haematoma:a reappraisal. Neurol India 49:3–10. [PubMed] [Google Scholar]
  • 106. Taoka T, Iwasaki S, Nakagawa H, Fukusumi A, Kitano S, Yoshioka T, Ohishi H, Uchida H, Nakani‐shi S, Hirai A (1996) Fast fluid‐attenuated inversion recovery (FAST‐FLAIR) of ischemic lesions in the brain: comparison with T2‐weighted turbo SE. Radiat Med 14:127–131. [PubMed] [Google Scholar]
  • 107. Thurman DJ, Alverson CA, Dunn KA, Guerrero J, Sniezek JE (1999) Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehab 14:602–615. [DOI] [PubMed] [Google Scholar]
  • 108. Varma S, Janesko KL, Wisniewski SR, Bayir H, Adelson PD, Thomas NJ, Kochanek PM (2003) F2‐isoprostane and neuron‐specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children. J Neurotrauma 20: 781–786. [DOI] [PubMed] [Google Scholar]
  • 109. Wilkinson AE, Bridges LR, Sivaloganathan S (1999) Correlation of survival time with size of axonal swellings in diffuse axonal injury. Acta Neuropathol (Berl) 98:197–202. [DOI] [PubMed] [Google Scholar]
  • 110. Willinger R, Ryan GA, McLean AJ, Kopp CM (1994) Mechanisms of brain injury related to mathematical modelling and epidemiological data. AccidAnal Prev 26:767–779. [DOI] [PubMed] [Google Scholar]
  • 111. Winter CD, Pringle AK, Clough GF, Church MK (2004) Raised parenchymal interleukin‐6 levels correlate with improved outcome after traumatic brain injury. Brain 127:315–320. [DOI] [PubMed] [Google Scholar]
  • 112. Yoshiya K, Tanaka H, Kasai K, Irisawa T, Shiozaki T, Sugimoto H (2003) Profile of gene expression in the subventricular zone after traumatic brain injury. J Neurotrauma 20:1147–1162. [DOI] [PubMed] [Google Scholar]
  • 113. Zhang L, Yang KH, King AI (2001) Biomechanics of neurotrauma. Neurol Res 23:144–156. [DOI] [PubMed] [Google Scholar]
  • 114. Zhang Y, Zou Y, Xu M, Zhu P, Wang Z (2000) Effect of endothelin and endothelin A receptors on regional cerebral blood flow after traumatic brain injury in rabbits. Chin J Traumatol 3:185–188. [PubMed] [Google Scholar]

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