title: Traumatically induced axonal damage: evidence for enduring changes in axolemmal permeability with associated cytoskeletal change.
abstract: Recent studies have demonstrated that delayed or secondary axotomy is a consistent feature of traumatic brain injury in both animals and man. Moreover, these studies have shown that the pathogenesis of this secondary axotomy involves various forms of initiating pathology, with the suggestion that, in some cases, only the axonal cytoskeleton is perturbed, while, in other cases, both the axonal cytoskeleton and related axolemma manifest traumatically induced perturbations. In the current communication, we continue in our investigation of the significance of these traumatically induced alterations in axolemmal permeability and their relation to any related intra-axonal cytoskeletal change. This was accomplished in cats which received intrathecal infusions of peroxidase, an agent normally excluded by the intact axolemma. These animals were subjected to traumatic brain injury, and sites showing altered axolemmal permeability to the peroxidase were assessed at the light and electron microscopic level. Through this approach, we recognized that a traumatic episode of moderate severity evoked changes in axolemmal permeability which surprising endured for up to 5 hrs postinjury. At such focal sites of altered permeability, the related cytoskeleton showed a statistically significantly neurofilament compaction, with the strong suggestion of concomitant neurofilament sidearm loss, microtubular dispersion, and mitochondrial abnormality. Over time, these events led to further disorganization of the axonal cytoskeleton which translated into impaired axoplasmic transport and secondary axotomy. Most likely, these alterations in axolemmal permeability result in either the direct or indirect effects upon the axonal cytoskeleton that precipitate the damaging sequences resulting in delayed axotomy.
authors.affiliation: Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Povlishock
authors.forename: E H
authors.initials: EH
authors.lastname: Pettus
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D001924:Brain Concussion / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000473:pathology*; D002415:Cats; D002463:Cell Membrane Permeability / Q000502:physiology*; D003599:Cytoskeleton / Q000648:ultrastructure*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008297:Male; D009454:Neurofibrils / Q000648:ultrastructure; D012183:Retrograde Degeneration / Q000502:physiology*; D013570:Synaptic Membranes / Q000648:ultrastructure
chemical_list: D006735:Horseradish Peroxidase