Traumatic Axonal Injury in the Spinal Cord Evoked by Traumatic Brain Injury

J Neurotrauma. 2008 Mar;25(3):205-13. doi: 10.1089/neu.2007.0331.


Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n = 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Axons / pathology*
  • Biomarkers / analysis
  • Brain Injuries / complications
  • Brain Injuries / physiopathology*
  • Brain Stem / injuries
  • Brain Stem / pathology
  • Brain Stem / physiopathology
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Immunohistochemistry
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology*
  • Time Factors
  • Wallerian Degeneration / etiology
  • Wallerian Degeneration / pathology*
  • Wallerian Degeneration / physiopathology*


  • Amyloid beta-Peptides
  • Biomarkers
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins