Immediate coma following inertial brain injury dependent on axonal damage in the brainstem

Restricted access

Object. Immediate and prolonged coma following brain trauma has been shown to result from diffuse axonal injury (DAI). However, the relationship between the distribution of axonal damage and posttraumatic coma has not been examined. In the present study, the authors examine that relationship.

Methods. To explore potential anatomical origins of posttraumatic coma, the authors used a model of inertial brain injury in the pig. Anesthetized miniature swine were subjected to a nonimpact-induced head rotational acceleration along either the coronal or axial plane (six pigs in each group). Immediate prolonged coma was consistently produced by head axial plane rotation, but not by head coronal plane rotation. Immunohistochemical examination of the injured brains revealed that DAI was produced by head rotation along both planes in all animals. However, extensive axonal damage in the brainstem was found in the pigs injured via head axial plane rotation. In these animals, the severity of coma was found to correlate with both the extent of axonal damage in the brainstem (p < 0.01) and the applied kinetic loading conditions (p < 0.001). No relationship was found between coma and the extent of axonal damage in other brain regions.

Conclusions. These results suggest that injury to axons in the brainstem plays a major role in induction of immediate posttraumatic coma and that DAI can occur without coma.

Article Information

Contributor Notes

Address reprint requests to: Douglas H. Smith, M.D., Department of Neurosurgery, University of Pennsylvania, 3320 Smith Walk, 105 Hayden Hall, Philadelphia, Pennsylvania 19104. email: smithdou@mail.med.upenn.edu.
Headings
References
  • 1.

    Adams JHDoyle DFord Iet al: Diffuse axonal injury in head injury: definition, diagnosis, and grading. Histopathology 15:49591989Adams JH Doyle D Ford I et al: Diffuse axonal injury in head injury: definition diagnosis and grading. Histopathology 15:49–59 1989

    • Search Google Scholar
    • Export Citation
  • 2.

    Adams JHDoyle DGraham DIet al: Diffuse axonal injury in head injuries caused by a fall. Lancet 2:142014221984Adams JH Doyle D Graham DI et al: Diffuse axonal injury in head injuries caused by a fall. Lancet 2:1420–1422 1984

    • Search Google Scholar
    • Export Citation
  • 3.

    Adams JHGraham DIGennarelli TA: Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl 32:15301983Adams JH Graham DI Gennarelli TA: Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl 32:15–30 1983

    • Search Google Scholar
    • Export Citation
  • 4.

    Alsop DCMurai HDetre JAet al: Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging. J Neurotrauma 13:5155211996Alsop DC Murai H Detre JA et al: Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging. J Neurotrauma 13:515–521 1996

    • Search Google Scholar
    • Export Citation
  • 5.

    Barzó PMarmarou AFatouros Pet al: Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg 87:9009071997Barzó P Marmarou A Fatouros P et al: Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg 87:900–907 1997

    • Search Google Scholar
    • Export Citation
  • 6.

    Blumbergs PCJones NRNorth JB: Diffuse axonal injury in head trauma. J Neurol Neurosurg Psychiatry 52:8388411989Blumbergs PC Jones NR North JB: Diffuse axonal injury in head trauma. J Neurol Neurosurg Psychiatry 52:838–841 1989

    • Search Google Scholar
    • Export Citation
  • 7.

    Cecil KMHills ECSandel MEet al: Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. J Neurosurg 88:7958011998Cecil KM Hills EC Sandel ME et al: Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. J Neurosurg 88:795–801 1998

    • Search Google Scholar
    • Export Citation
  • 8.

    Cecil KMLenkinski REMeaney DFet al: High field proton magnetic resonance spectroscopy of a swine model for axonal injury. J Neurochem 70:203820441998Cecil KM Lenkinski RE Meaney DF et al: High field proton magnetic resonance spectroscopy of a swine model for axonal injury. J Neurochem 70:2038–2044 1998

    • Search Google Scholar
    • Export Citation
  • 9.

    Chen XHMeaney DFXu BNet al: Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:5885961999Chen XH Meaney DF Xu BN et al: Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:588–596 1999

    • Search Google Scholar
    • Export Citation
  • 10.

    Clifton GLKreutzer JSChoi SCet al: Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury. Neurosurgery 33:34391993Clifton GL Kreutzer JS Choi SC et al: Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury. Neurosurgery 33:34–39 1993

    • Search Google Scholar
    • Export Citation
  • 11.

    Gennarelli TA: Mechanisms of brain injury. J Emerg Med 11 (Suppl 1):5111993Gennarelli TA: Mechanisms of brain injury. J Emerg Med 11 (Suppl 1):5–11 1993

    • Search Google Scholar
    • Export Citation
  • 12.

    Gennarelli TAThibault LEAdams JHet al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:5645741982Gennarelli TA Thibault LE Adams JH et al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:564–574 1982

    • Search Google Scholar
    • Export Citation
  • 13.

    Gentry LRGodersky JCThompson BH: Traumatic brain stem injury: MR imaging. Radiology 171:1771871989Gentry LR Godersky JC Thompson BH: Traumatic brain stem injury: MR imaging. Radiology 171:177–187 1989

    • Search Google Scholar
    • Export Citation
  • 14.

    Grady SMMcLaughlin MRChristman CWet al: The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans. J Neuropathol Exp Neurol 52:1431521993Grady SM McLaughlin MR Christman CW et al: The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans. J Neuropathol Exp Neurol 52:143–152 1993

    • Search Google Scholar
    • Export Citation
  • 15.

    Graham DIMcLellan DAdams JHet al: The neuropathology of the vegetative state and severe disability after non-missile head injury. Acta Neurochir Suppl 32:65671983Graham DI McLellan D Adams JH et al: The neuropathology of the vegetative state and severe disability after non-missile head injury. Acta Neurochir Suppl 32:65–67 1983

    • Search Google Scholar
    • Export Citation
  • 16.

    Hanstock CCFaden AIBendall MRet al: Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue. Stroke 25:8438481994Hanstock CC Faden AI Bendall MR et al: Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue. Stroke 25:843–848 1994

    • Search Google Scholar
    • Export Citation
  • 17.

    Karnaze DSWeiner JMMarshall LF: Auditory evoked potentials in coma after closed head injury: a clinical-neurophysiologic coma scale for predicting outcome. Neurology 35:112211261985Karnaze DS Weiner JM Marshall LF: Auditory evoked potentials in coma after closed head injury: a clinical-neurophysiologic coma scale for predicting outcome. Neurology 35:1122–1126 1985

    • Search Google Scholar
    • Export Citation
  • 18.

    Kimura HMeaney DFMcGowan JCet al: Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation. J Comput Assist Tomogr 20:5405461996Kimura H Meaney DF McGowan JC et al: Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation. J Comput Assist Tomogr 20:540–546 1996

    • Search Google Scholar
    • Export Citation
  • 19.

    McGowan JCMcCormack TMGrossman RIet al: Diffuse axonal pathology detected with magnetization transfer imaging following brain trauma in the pig. Magn Reson Imaging 41:7277331999McGowan JC McCormack TM Grossman RI et al: Diffuse axonal pathology detected with magnetization transfer imaging following brain trauma in the pig. Magn Reson Imaging 41:727–733 1999

    • Search Google Scholar
    • Export Citation
  • 20.

    Miller RTMargulies SSLeoni Met al: Finite element modeling approaches for predicting injury in an experimental model of severe diffuse axonal injury in Society of Automotive Engineers (ed): 42nd Stapp Car Crash Conference Proceedings (P-337). SAE Tehnical Paper Series 983154. Warrandale, PA: Society of Automotive Engineers1998 pp 155167Miller RT Margulies SS Leoni M et al: Finite element modeling approaches for predicting injury in an experimental model of severe diffuse axonal injury in Society of Automotive Engineers (ed):42nd Stapp Car Crash Conference Proceedings (P-337). SAE Tehnical Paper Series 983154. Warrandale PA: Society of Automotive Engineers 1998 pp 155–167

    • Search Google Scholar
    • Export Citation
  • 21.

    Mittl RLGrossman RIHiehle JFet al: Prevalence of MR evidence of diffuse axonal injury in patients head injury and normal head CT findings. AJNR 15:158315891994Mittl RL Grossman RI Hiehle JF et al: Prevalence of MR evidence of diffuse axonal injury in patients head injury and normal head CT findings. AJNR 15:1583–1589 1994

    • Search Google Scholar
    • Export Citation
  • 22.

    Povlishock JTBecker DPCheng CLYet al: Axonal change in minor head injury. J Neuropathol Exp Neurol 42:2252421983Povlishock JT Becker DP Cheng CLY et al: Axonal change in minor head injury. J Neuropathol Exp Neurol 42:225–242 1983

    • Search Google Scholar
    • Export Citation
  • 23.

    Servadei PVergoni GPasini Aet al: Diffuse axonal injury with brainstem localisation: report of a case in a mild head injured patient. J Neurosurg Sci 38:1291301994Servadei P Vergoni G Pasini A et al: Diffuse axonal injury with brainstem localisation: report of a case in a mild head injured patient. J Neurosurg Sci 38:129–130 1994

    • Search Google Scholar
    • Export Citation
  • 24.

    Smith DHCecil KMMeaney DFet al: Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J Neurotrauma 15:6656741998Smith DH Cecil KM Meaney DF et al: Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J Neurotrauma 15:665–674 1998

    • Search Google Scholar
    • Export Citation
  • 25.

    Smith DHChen XHNonaka Met al: Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:9829921999Smith DH Chen XH Nonaka M et al: Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:982–992 1999

    • Search Google Scholar
    • Export Citation
  • 26.

    Smith DHChen XHXu BNet al: Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig. J Neuropathol Exp Neurol 56:8228341997Smith DH Chen XH Xu BN et al: Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig. J Neuropathol Exp Neurol 56:822–834 1997

    • Search Google Scholar
    • Export Citation
  • 27.

    Sosin DMSacks JJSmith SM: Head injury-associated deaths in the United States from 1979 to 1986. JAMA 262:225122551989Sosin DM Sacks JJ Smith SM: Head injury-associated deaths in the United States from 1979 to 1986. JAMA 262:2251–2255 1989

    • Search Google Scholar
    • Export Citation
  • 28.

    Sosin DMSniezek JEWaxweiler RJ: Trends in death associated with traumatic brain injury, 1979 through 1992. Success and failure. JAMA 273:177817801995Sosin DM Sniezek JE Waxweiler RJ: Trends in death associated with traumatic brain injury 1979 through 1992. Success and failure. JAMA 273:1778–1780 1995

    • Search Google Scholar
    • Export Citation
  • 29.

    Yoshikawa T: The Brain of the Pig. Atlas of the Brains of Domestic Animals Vol 5Sect 1.Tokyo: University of Tokyo Press1968 pp 132Yoshikawa T: The Brain of the Pig. Atlas of the Brains of Domestic Animals Vol 5 Sect 1. Tokyo: University of Tokyo Press 1968 pp 1–32

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 451 419 16
Full Text Views 285 129 5
PDF Downloads 167 59 4
EPUB Downloads 0 0 0
PubMed
Google Scholar