title: Histopathological changes at central nodes of Ranvier after stretch-injury.
abstract: While the brain readily deforms when exposed to rotational loads as experienced in violent movements of the head, axons are able only to sustain tensile loads. Two discrete classes of axonal injury have been posited: disruptive axonal injury, where axons are physically torn or fragmented at the time of the insult, and nondisruptive axonal injury, where there is a hypothesised "perturbation" of the axolemma which leads to a cascade of pathobiological changes which result in axotomy over a period between 2 and 24 h after the initial insult. In the latter, it is posited that the node of Ranvier is that part of the axon which is the initial locus of axonal damage/ histopathological change. This paper describes the ultrastructure of nodal blebs, axolemma limited protrusions of the nodal axoplasm into the perinodal space, in which the nodal dense undercoating has been lost and aggregates of membranous profiles occur within the axoplasm. In addition, this paper provides novel data for disruption of the axonal cytoskeleton in nodes where blebs occur within 15 min of stretch-injury. The cytoskeletal disruption is visualised in thin sections as an almost total loss of microtubules together with a reduced density of neurofilaments within the nodal axoplasm. The loss of microtubules is posited to result in a disruption of fast axonal transport which results in the focal accumulation of membranous organelles in adjacent paranodal regions of the axon to form so-called "axonal swellings." Cytochemical and freeze-fracture studies provide evidence for structural reorganisation of the nodal axolemma after stretch-injury, and it is posited that these changes provide a route for uncontrolled influx of calcium which leads to loss of axonal integrity which potentiates axotomy. It is suggested that increased understanding of regulatory mechanisms that control ion channel activity will greatly increase our understanding of responses of neurones to trauma.
authors.affiliation: Laboratory of Human Anatomy, University of Glasgow, United Kingdom.
authors.forename: W L
authors.initials: WL
authors.lastname: Maxwell
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006168:Guinea Pigs; D008870:Microtubules / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D011323:Primates; D011901:Ranvier's Nodes / Q000473:pathology*; D013718:Tensile Strength
chemical_list: D016900:Neurofilament Proteins; D000252:Calcium-Transporting ATPases; D002118:Calcium