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- Title
The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury.
- Authors
McPhail, Lowell T.; Stirling, David P.; Tetzlaff, Wolfram; Kwiecien, Jacek M.; Ramer, Matt S.
- Abstract
Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long–Evans Shaker rat is a naturally occurring dysmyelinated mutant, which although able to express the components of myelin lacks functional myelin in adulthood. Given that myelin breakdown exposes axons to molecules that are inhibitory to regeneration, we sought to determine whether injured dorsal column axons in a Shaker rat would exhibit a regenerative response absent in normally myelinated Long–Evans (control) rats. Although Shaker rat axons did not regenerate beyond the lesion, they remained at the caudal end of the crush site. Control rat axons, in contrast, retracted and died back from the edge of the crush. The absence of retraction/dieback in Shaker rats was associated with a reduced phagocytic reaction to dorsal column crush around the caudal edge of the lesion. Systemic injection of minocycline, a tetracycline derivative, in control rats reduced both the macrophage response and axonal retraction/dieback following dorsal column injury. In contrast, increasing macrophage activation by spinal injection of the yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker rats. Schwann cell invasion was reduced in minocycline-treated control rats compared with untreated control rats, and was almost undetectable in Shaker rats, suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration is dependent upon macrophage-mediated myelin degeneration. These results indicate that following spinal cord injury the phagocyte-mediated degeneration of myelin and subsequent exposure of inhibitory molecules to the injured axons contributes to their retraction/dieback.
- Subjects
PHAGOCYTES; MYELIN proteins; AXONS; LABORATORY rats; CENTRAL nervous system; TETRACYCLINE
- Publication
European Journal of Neuroscience, 2004, Vol 20, Issue 8, p1984
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2004.03662.x