ADHESIVE REPULSIVE PROPERTIES IN THE INJURED SPINAL-CORD - RELATION TO MYELIN PHAGOCYTOSIS BY INVADING MACROPHAGES/

The vigorous ingrowth of cut CNS axons into peripheral nerve grafts in dicates that the lack of neuronal regeneration within the brain and sp inal cord cannot be explained merely by CNS neurons having an inherent weak regenerative capacity. Rather, the brain and spinal cord seem to contain molecules that inhibit axonal growth and, indeed, oligodendro cyte myelin has been demonstrated to effectively block nerve fiber gro wth. Macrophages can in vitro counteract this growth prohibitorty prop erty of the CNS. In this study we have examined the recruitment of mac rophages and the removal of myelin in relation to neurite adhesive/rep ulsive properties in the injured spinal cord of adult rats. Cells immu noreactive for the macrophage-specific antibody ED1 rapidly invaded th e lesion area after an incision in the dorsal or ventral funiculus. Th e number of macrophages remained high for several weeks in the scar ti ssue formed after both these injuries. This type of scar tissue has pr eviously been reported to permit ingrowth and long-term persistence of axons. In the denervated area rostral to a dorsal funiculus transecti on, no or few ED1-immunoreactive cells were detected within the first month after the injury. However, at subsequent stages an increasing nu mber of macrophages was found in this region. Myelin was removed much more rapidly at the site of the lesion than rostral to this (in the ar ea undergoing Wallerian degeneration). In order to study adhesive/repu lsive properties in the injured spinal cord in relation to local myeli n content we employed an in vitro system in which PC12 cells were cult ured on spinal cord slices. PC12 cells failed to adhere to sections fr om the intact spinal cord as well as to sections taken rostral to a do rsal funiculus transection, whereas many cells adhered to the glial sc ar formed at the lesion. Even at 15 months after the injury, very few PC12 cells attached to sections taken rostral to the transection despi te the fact that no myelin could be detected in the denervated area at that time. These data suggest that, in addition to myelin-related gro wth inhibitory molecules, other factors may be involved in the failure of PC12 cells to adhere to the denervated spinal cord. Such factors c ould also affect axonal regrowth after spinal cord injury. The adhesio n of PC12 cells to the lesion area may be a result of a locally high c ontent of extracellular matrix molecules and/or cell adhesion molecule s, factors which are not expressed in the region undergoing Wallerian degeneration. (C) 1994 Academic Press, Inc.