title: Stereology and ultrastructure of chronic phase axonal and cell soma pathology in stretch-injured central nerve fibers.
abstract: Magnetic resonance imaging (MRI) suggests that with survival after human traumatic brain injury (TBI), there is ongoing loss of white and grey matter from the injured brain during the chronic phase. However; direct quantitative experimental evidence in support of this observation is lacking. Using the guinea pig stretch-injury optic nerve model, quantitative evidence by stereology of damage to the optic nerve and retina was sought. Stretch injury was applied to the right optic nerve of 15 adult male guinea pigs. Three animals each at 1, 2, 3, 8, or 12 weeks' survival were killed and prepared for transmission electron microscopy (TEM). The estimated number of intact and injured axons within bins of transverse diameters 0-0.5, 0.51-1.0, 1.01-1.5, 1.51-2.0, 2.01-2.5, and 2.51-3.0 μm in the middle segment of each injured optic nerve and from 5 control animals were compared across all survival time points. The estimated numbers of intact and pyknotic retinal ganglion cells from the same animals were also compared. Loss of myelinated fibers continued throughout the experimental period. The most rapid loss was of the largest fibers; loss of intermediate-sized fibers continued, but the numbers of the smallest fibers increased from 3 weeks onward. There was hypertrophy and proliferation of glial cells within the surrounding neuropil. A relatively low-grade loss of retinal ganglion cells occurred throughout the experiment, with about 60% remaining at 12 weeks' survival. We provide quantitative evidence that after traumatic axonal injury (TAI) there is a continuing loss of nerve fibers and their cell bodies from a CNS tract over a 3-month post-traumatic interval.
authors.affiliation: Department of Anatomy, College of Medicine, Veterinary Medicine and Life Sciences, Thomson Building, University of Glasgow, Glasgow, Scotland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mohammed Sulaiman
authors.forename: Nicola
authors.initials: N
authors.lastname: Denman
authors.forename: Shaun
authors.initials: S
authors.lastname: Buchanan
authors.forename: Nicola
authors.initials: N
authors.lastname: Porter
authors.forename: Sauparnika
authors.initials: S
authors.lastname: Vijay
authors.forename: Sauparnika
authors.initials: S
authors.lastname: Vesi
authors.forename: Rachel
authors.initials: R
authors.lastname: Sharpe
authors.forename: David I
authors.initials: DI
authors.lastname: Graham
authors.forename: William L
authors.initials: WL
authors.lastname: Maxwell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure*; D006168:Guinea Pigs; D008279:Magnetic Resonance Imaging; D008297:Male; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009900:Optic Nerve / Q000473:pathology* / Q000648:ultrastructure*; D020221:Optic Nerve Injuries / Q000473:pathology*; D012160:Retina / Q000473:pathology / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000648:ultrastructure