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

View More View Less
  • 1 Departments of Neurosurgery, Bioengineering, and Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

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.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

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.
  • 1.

    Adams JH, , Doyle D, & Ford I, et al: Diffuse axonal injury in head injury: definition, diagnosis, and grading. Histopathology 15:4959, 1989 Adams 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 JH, , Doyle D, & Graham DI, et al: Diffuse axonal injury in head injuries caused by a fall. Lancet 2:14201422, 1984 Adams 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 JH, , Graham DI, & Gennarelli TA: Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl 32:1530, 1983 Adams 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 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 13:515521, 1996 Alsop 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 P, , Marmarou A, & Fatouros P, et al: Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg 87:900907, 1997 Barzó 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 PC, , Jones NR, & North JB: Diffuse axonal injury in head trauma. J Neurol Neurosurg Psychiatry 52:838841, 1989 Blumbergs 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 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 88:795801, 1998 Cecil 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 KM, , Lenkinski RE, & Meaney DF, et al: High field proton magnetic resonance spectroscopy of a swine model for axonal injury. J Neurochem 70:20382044, 1998 Cecil 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 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 58:588596, 1999 Chen 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 GL, , Kreutzer JS, & Choi SC, et al: Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury. Neurosurgery 33:3439, 1993 Clifton 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):511, 1993 Gennarelli TA: Mechanisms of brain injury. J Emerg Med 11 (Suppl 1):5–11, 1993

    • Search Google Scholar
    • Export Citation
  • 12.

    Gennarelli TA, , Thibault LE, & Adams JH, et al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:564574, 1982 Gennarelli 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 LR, , Godersky JC, & Thompson BH: Traumatic brain stem injury: MR imaging. Radiology 171:177187, 1989 Gentry LR, Godersky JC, Thompson BH: Traumatic brain stem injury: MR imaging. Radiology 171:177–187, 1989

    • Search Google Scholar
    • Export Citation
  • 14.

    Grady 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 52:143152, 1993 Grady 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 DI, , McLellan D, & Adams JH, et al: The neuropathology of the vegetative state and severe disability after non-missile head injury. Acta Neurochir Suppl 32:6567, 1983 Graham 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 CC, , Faden AI, & Bendall MR, et al: Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue. Stroke 25:843848, 1994 Hanstock 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 DS, , Weiner JM, & Marshall LF: Auditory evoked potentials in coma after closed head injury: a clinical-neurophysiologic coma scale for predicting outcome. Neurology 35:11221126, 1985 Karnaze 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 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 20:540546, 1996 Kimura 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 JC, , McCormack TM, & Grossman RI, et al: Diffuse axonal pathology detected with magnetization transfer imaging following brain trauma in the pig. Magn Reson Imaging 41:727733, 1999 McGowan 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 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 155167 Miller 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 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 15:15831589, 1994 Mittl 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 JT, , Becker DP, & Cheng CLY, et al: Axonal change in minor head injury. J Neuropathol Exp Neurol 42:225242, 1983 Povlishock 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 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 38:129130, 1994 Servadei 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 DH, , Cecil KM, & Meaney DF, et al: Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J Neurotrauma 15:665674, 1998 Smith 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 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 58:982992, 1999 Smith 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 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 56:822834, 1997 Smith 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 DM, , Sacks JJ, & Smith SM: Head injury-associated deaths in the United States from 1979 to 1986. JAMA 262:22512255, 1989 Sosin 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 DM, , Sniezek JE, & Waxweiler RJ: Trends in death associated with traumatic brain injury, 1979 through 1992. Success and failure. JAMA 273:17781780, 1995 Sosin 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 5, Sect 1.Tokyo: University of Tokyo Press, 1968, pp 132 Yoshikawa 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

Metrics

All Time Past Year Past 30 Days
Abstract Views 620 228 10
Full Text Views 305 36 1
PDF Downloads 179 27 1
EPUB Downloads 0 0 0