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Impact Acceleration Injury in the Rat: Evidence for Focal Axolemmal Change and Related Neurofilament Sidearm Alteration

J. T. Povlishock PhD, A. Marmarou PhD, T. McIntosh PhD, J. Q. Trojanowski MD, PhD, J. Moroi MD
DOI: http://dx.doi.org/10.1097/00005072-199704000-00003 347-359 First published online: 1 April 1997

Abstract

Recently we reported that traumatic brain injury evokes local changes in the axolemma's permeability, in concert with local cytoskeletal changes involving neurofilament (NF) compaction and sidearm loss, all of which contribute to the genesis of reactive axonal change. Since it was of concern that these events may be either injury model- or species-specific, we sought to address these phenomena in a different but well-characterized animal model and species. Further, to provide more compelling insight into the potential for NF compaction and sidearm alteration, we also employed antibodies specific for the NF rod domains, which are readily visualized only when the NF sidearms are disturbed. Rats were subjected to impact acceleration injury. To assess the potential for altered axolemmal permeability, 5 animals received intrathecal horseradish peroxidase (HRP), normally excluded by the intact axolemma. To assess the potential for NF sidearm alteration, another 14 animals were processed for the visualization of antibodies targeting the NF rod domain at 5 minutes (min) to 24 hours (h) postinjury. All animals were evaluated at the LM and EM levels. Those animals receiving intrathecal HRP showed immediate focal alterations in the axolemma's permeability to the normally excluded tracer. Over a 2 h period, these axons demonstrated NF compaction. Antibodies targeted to the rod domains revealed focal intra-axonal immunoreactivity in sites closely correlated with those showing altered axolemmal permeability. These same sites also demonstrated evidence of NF compaction and sidearm loss/perturbation. Collectively, these findings suggest that occurrence of altered axolemmal permeability and concomitant cytoskeletal change are features common to traumatic brain injury in various animal models and species. Further, these studies underscore the utility of antibodies targeting the rod domain for the early detection of traumatically induced reactive change.

Key Words
  • Axolemmal permeability
  • Cytoskeleton
  • Immunocytochemistry
  • Rat
  • Traumatic brain injury