Genetic influences on cellular reactions to spinal cord injury: a wound-healing response present in normal mice is impaired in mice carrying a mutation (WldS) that causes delayed Wallerian degeneration.
Progressive tissue necrosis is a process unique to the injured mammalian spinal cord which often leads to gradually increasing cavitation and enlargement of the lesion. To evaluate the role of neuronal degeneration in initiating this response, histopathological changes were compared in C57BL and WldS (delayed Wallerian degeneration mutation) mice. The spinal cord was crushed at T8, producing a primary lesion at the site of the trauma and a secondary lesion extending rostrocaudally in the dorsal columns (where long ascending and descending fiber tracts undergo Wallerian degeneration). Cavitation was relatively mild at both sites and developed mainly at the margins of the lesions. In striking contrast to spinal cord injury in rats, progressive necrosis did not occur in mice; instead, the primary and secondary lesion sites became filled in by macrophages and fibroblasts embedded in a well-vascularized collagenous stroma. Quantitative image analysis revealed that the primary lesion decreased dramatically in size and cavitation between 2 and 3 weeks in C57BL, whereas in WldS the reduction in size and cavitation began later (at 4 weeks) and was less complete. The initial development of the secondary lesion began later and its healing was less complete in WldS than C57BL. These results are consistent with the hypothesis that neuronal damage, including Wallerian degeneration, triggers inflammatory responses leading to tissue repair. For this reason, any delay in neuronal degeneration, as in the WldS mutation, results in deficient tissue repair as reflected in the larger size of both primary and dorsal column lesions.
Zhang
Z
Z
Department of Biology, College of William and Mary, Williamsburg, Virginia 23187, USA.
Fujiki
M
M
Guth
L
L
Steward
O
O
D000818:Animals; D005069:Evaluation Studies as Topic; D005260:Female; D007091:Image Processing, Computer-Assisted; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D013045:Species Specificity; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology; D014855:Wallerian Degeneration / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics*