title: Responses in the guinea pig optic nerve four hours after stretch-injury
Creators: name: Seyed Jafari, Seyed Saeed
Publisher: name: University of Glasgow
Year: 1998
Subjects: subject: Neurosciences.

description: Morphological and quantitative morphometric analysis of changes 4 hours after traumatic axonal injury (TAI) in stretch-injury to guinea pig optic nerve fibres, a model of human diffuse axonal injury (DAI), demonstrated that the response of different sizes of axons/fibres with particular respect to the axonal cytoskeleton differed. The site of maximum axonal/fibre damage was found to be in the middle rather than the prechiasmatic portion of the guinea pig optic nerve. The number of axons with a diameter &lt; 0.50 mum increased significantly after stretch-injury. Neurofilament compaction occurred in smaller axons with a diameter of less than 1.50mum. In the axons with a diameter &lt; 0.50 mum compaction of neurofilaments was associated with a reduction in both axonal calibre and the g-ratio, and associated with an increase in the number of myelin lamellae. In axons with a diameter of less than 1.00 mum neurofilament compaction was associated with a significant increase in the number of neurofilaments. The degree of neurofilament compaction decreased with increasing axonal size. In the majority of larger fibres (axonal diameter &gt; 2.00 mum) compaction of neurofilaments did not occur, but rather there was a significant increase in spacing between neighbouring, neurofilaments, referred to as "dispersion", that was associated with a significant loss of their number. In a small proportion of larger fibres, in which periaxonal space(s) occurred, there was, however, compaction of neurofilaments rather than an increase in their spacing. This was associated with a significant reduction in both axonal calibre and the g-ratio, but without any change in the number of myelin lamellae. Longitudinal thin sections revealed that there were local foci of compaction of neurofilaments along the length of some nerve fibres that were separated from regions where the appearance of the fibre was close to normal. At these foci, compaction of neurofilaments was associated with the occurrence of large holes in the axolemma, separation of the axolemma from the remnants of the cytoskeleton and loss of the close relationship of the axolemma to the myelin sheath. The myelin sheath at these foci was grossly disrupted and expanded to form a "balloon-like" appearance. The response of microtubules differed from that of neurofilaments after stretch-injury. There was an apparent increase in spacing between microtubules in fibres with an axonal diameter less than 1.50 ?im and decrease in their number in fibres with axonal diameter less than 2.00 mum, however these changes were not statistically significant. There was a significant increase in spacing between microtubules in fibres with an axonal diameter greater than 1.50 mum. There was a loss in their number in both larger fibres (diameter &gt; 2.00 mum) with dispersion of neurofilaments and those with periaxonal space(s) where compaction of neurofilaments occurred. It is hypothesised that there is a spectrum of axonal damage. At milder levels of injury there is misalignment of the cytoskeleton, at more severe levels compaction of neurofilaments, loss of microtubules and fragmentation of the axolemma. Morphological and morphometric analysis provided novel data which demonstrated that (i) the response by neurofilaments differed in different sizes of axons/fibres, (ii) that the neurofilament response differed along the length of the same axon, and (iii) the response by microtubules to stretch-injury differed from that of neurofilaments. The present study provides the first evidence that there is indeed a spectrum of pathological changes in different sizes of axons/fibres 4 hours after traumatic axonal injury to guinea pig optic nerves.