Research reportAlteration of the neurofilament sidearm and its relation to neurofilament compaction occurring with traumatic axonal injury
Introduction
In a recent communication, we have evaluated those intra-axonal events that lead to the genesis of delayed axonal swelling and disconnection associated with traumatically-induced injury 11, 12, 14. In these studies we demonstrated that the traumatic episode evokes two distinct sets of focal intra-axonal cytoskeletal change in the first minutes post injury; one involving rapid focal misalignment of the cytoskeleton, the other involving a focal compaction of the neurofilaments (NF) and concomitant microtubular (MT) loss. In the case of cytoskeletal misalignment, these changes occurred independent of any overt alterations of axolemmal permeability and the pathobiology appeared restricted to the intra-axonal domain. However, in those axons exhibiting focal NF compaction and MT loss, concomitant changes in focal axolemmal permeability occurred, suggesting that an alteration of the axoplasmic milieu via the influx of extracellular agents precipitated proteolytic cleavage of the NF sidearms.
In this scenario, we posited the loss of NF sidearms and their stearic hindrance allowed for the collapse of NF and their rapid compaction [12]. Although this scenario appeared credible and provided insight into potential mediators of the observed cytoskeletal collapse, it is noteworthy that no direct studies were performed on the NF sidearms in relation to this process of NF compaction. This shortcoming was related, in part, to the fact that such studies are labor-intensive and, moreover, rely on ultra-high magnification EM to confirm the morphology of the sidearm and its specific relation to the adjacent NF.
Appreciating that the issue of NF sidearm change should be addressed to generate a comprehensive understanding of the pathobiology of traumatically-induced axonal change, we have initiated, in the present communication, a detailed study of the NF sidearms in foci of NF compaction as well as other non-injured axonal segments. Using digitized electron micrographs generated from those axons previously evaluated for evidence of traumatically-induced axonal change and NF compaction, we reconstructed the NF sidearms via computer-assisted enlargement and assessed their morphology in relation to the observed compaction. Further quantitative analysis of sidearm height was performed to gain a better impression of their change ongoing in relation to the observed abnormalities. In the following passages we report our findings in relation to these NF sidearm changes.
Section snippets
Animal preparation and injury
The materials used in the current communication relied on electron micrographs harvested from sites of NF compaction gathered as a part of our previous communication focusing on those axolemmal and intra-axonal ultrastructural changes occurring with traumatically-induced axonal injury. To identify such injured axons our previous studies utilized extracellular macromolecules such as horseradish peroxidase (HRP) normally excluded by the intact, uninjured axolemma [11]. The premise of this
Control axons
When these images were videographically captured, digitized, and enlarged to a magnification of approximately 800 000×, fields of non-HRP-containing uninjured axons displayed cytoskeletal detail consistent with that previously described in non-injured axons (Fig. 1b). Long, straight NF (Fig. 1b) with prominent sidearms were readily identified. NF were linear with constant interfilament distances and did not move in and out of the plane of section.
Flooded axons
At a magnification of 800 000×, the NF of
Discussion
The results of the current communication show in a convincing fashion that NF compaction is associated with a change in the overall height of the sidearms but, interestingly, does not involve a complete loss or cleavage of sidearms, as we had proposed previously 11, 12. Previously, we had demonstrated that one characteristic feature of traumatically-induced axonal pathology, associated with altered axolemmal permeability, was NF compaction and MT loss. Our working assumption was that, in this
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