title: Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury.
abstract: Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal axolemma. By 4 h, there was novel labeling for Ca-ATPase membrane pump activity at the same site. There was loss of IMPs from the nodal axolemma extending over several hours after injury. There was loss of both membrane pump Ca-ATPase and p-nitro-phenylphosphatase (p-NPPase) activity of the node. There was loss of ecto-Ca-ATPase activity but increased labeling for p-NPPase activity at sites of dissociation of compacted myelin. Quantitative freeze-fracture demonstrated statistically significant changes in membrane structure. We provide support for the hypothesis that structural and functional changes occur in the axolemma and myelin sheath at nondisruptive axonal injury.
authors.affiliation: Laboratory of Human Anatomy, University of Glasgow, U.K.
authors.forename: W L
authors.initials: WL
authors.lastname: Maxwell
authors.forename: R
authors.initials: R
authors.lastname: Kosanlavit
authors.forename: B J
authors.initials: BJ
authors.lastname: McCreath
authors.forename: O
authors.initials: O
authors.lastname: Reid
authors.forename: D I
authors.initials: DI
authors.lastname: Graham
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D018450:Disease Progression; D005614:Freeze Fracturing; D006168:Guinea Pigs; D006706:Homeostasis; D008297:Male; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009900:Optic Nerve / Q000378:metabolism / Q000648:ultrastructure; D020221:Optic Nerve Injuries; D011901:Ranvier's Nodes / Q000378:metabolism / Q000648:ultrastructure; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D009597:4-Nitrophenylphosphatase; D000252:Calcium-Transporting ATPases