title: Post-acute alterations in the axonal cytoskeleton after traumatic axonal injury.
abstract: All previous analyses of axonal responses to traumatic axonal injury (TAI) have described the ultrastructure of changes in the cytoskeleton and axolemma within 6 h of injury. In the present study we tested the hypothesis that there are, in addition, ultrastructural pathological changes up to 1 week after injury. TAI was induced in the adult guinea pig optic nerve of nine animals. Three animals were killed at either 4 h, 24 h, or 7 days (d) after injury. Quantitative analysis of the number or proportion of axons within 0.5-micro m-wide bins showed an increase in the number of axons with a diameter of less than 0.5 micro m at 4 h, 24 h, and 7 d, the presence of lucent axons at 24 h and 7 d and that the highest number of injured axons occurred about half way along the length of the nerve. A spectrum of pathological changes occurred in injured fibers-pathology of mitochondria; dissociation of myelin lamellae but little damage to the axon; loss of linear register of the axonal cytoskeleton; differential responses between microtubules (MT) and neurofilaments (NF) in different sizes of axon; two different sites of compaction of NF; loss of both NF (with an increase in their spacing) and MT (with a reduction in their spacing); replacement of the axoplasm by a flocculent precipitate; and an increased length of the nodal gap. These provide the first ultrastructural evidence for Wallerian degeneration of nerve fibers in an animal model of TAI.
authors.affiliation: Laboratory of Human Anatomy, Division of Neuroscience, IBLS, University of Glasgow, Glasgow, United Kingdom. wmaxwell@bio.gla.ac.uk
authors.forename: William L
authors.initials: WL
authors.lastname: Maxwell
authors.forename: Aisha
authors.initials: A
authors.lastname: Domleo
authors.forename: Gillian
authors.initials: G
authors.lastname: McColl
authors.forename: Saeed S
authors.initials: SS
authors.lastname: Jafari
authors.forename: David I
authors.initials: DI
authors.lastname: Graham
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000648:ultrastructure*; D006168:Guinea Pigs; D008297:Male; D009412:Nerve Fibers / Q000473:pathology; D020221:Optic Nerve Injuries / Q000473:pathology*; D012016:Reference Values; D014855:Wallerian Degeneration / Q000473:pathology