Because of its non-invasive nature and ease of regulation, a closely monitored cryogenic method of tissue injury was used to create a degree of spinal cord injury within which there would be an extended regrowth of axons. The parameters of cooling used in the present study resulted in an injury length of 1 cm through which 3 mm of measured axonal regrowth and 8 mm of observed regrowth occurred over a 56-day period in the ascending fibers of the dorsal column of the mature rat. This was associated with the development of a cellular matrix consisting of macrophages, macroglia and Schwann cells which gradually expands within the injured area initially dominated by macrophages. It is the authors' impression that the presence of a substantial microglial component within the macrophage population may be a significant factor in the success of the axonal regrowth. Under this influence and that of the invading axons, the astrocyte, which provides the immediate cell support to the growing axon, can be maintained in a functional state that is supportive and not obstructive to the axon, presumably through the recruitment of astrocyte precursors from an indigenous stem cell population. These tissue changes indicate that adult mammalian spinal cord tissue does have the capacity to develop on its own a matrix capable of supporting the regrowth of axons.
Cryogenic injury of adult, rat spinal cord was produced under controlled non-invasive conditions to study repair and regeneration in adult, mammalian central nervous tissue in which tissue continuity and integrity are relatively preserved. Under these experimental conditions axons and myelin are destroyed, a matrix of glial cells is preserved, and regrowth of axons is apparent. Electron microscopic studies at 7, 15, 30 and 60 days post-injury demonstrate axonal structures indicative of regrowth, astrocytic structures which appear to provide support to both matrix and axons and myelination of axons by both oligodendrocytes and Schwann cells. These cellular events restore much of the normal structure within the injured area up to its junction with the Wallerian zone. In this junctional zone morphologic evidence may indicate continuing cellular activity, even at 60 days, in axons, astrocytes and myelinating cells. These studies suggest that under ideal conditions damaged axons may be capable of regeneration within the adult mammalian central nervous system and that this model provides an opportunity to define some of the mechanisms.
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