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 indicates that the lack of neuronal regeneration within the brain and spinal 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, oligodendrocyte myelin has been demonstrated to effectively block nerve fiber growth. Macrophages can in vitro counteract this growth prohibitory property of the CNS. In this study we have examined the recruitment of macrophages and the removal of myelin in relation to neurite adhesive/repulsive properties in the injured spinal cord of adult rats. Cells immunoreactive for the macrophage-specific antibody ED1 rapidly invaded the lesion area after an incision in the dorsal or ventral funiculus. The number of macrophages remained high for several weeks in the scar tissue formed after both these injuries. This type of scar tissue has previously been reported to permit ingrowth and long-term persistence of axons. In the denervated area rostral to a dorsal funiculus transection, no or few ED1-immunoreactive cells were detected within the first month after the injury. However, at subsequent stages an increasing number 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 area undergoing Wallerian degeneration). In order to study adhesive/repulsive properties in the injured spinal cord in relation to local myelin content we employed an in vitro system in which PC12 cells were cultured on spinal cord slices. PC12 cells failed to adhere to sections from the intact spinal cord as well as to sections taken rostral to a dorsal funiculus transection, whereas many cells adhered to the glial scar formed at the lesion. Even at 15 months after the injury, very few PC12 cells attached to sections taken rostral to the transection despite the fact that no myelin could be detected in the denervated area at that time. These data suggest that, in addition to myelin-related growth inhibitory molecules, other factors may be involved in the failure of PC12 cells to adhere to the denervated spinal cord. Such factors could also affect axonal regrowth after spinal cord injury. The adhesion of PC12 cells to the lesion area may be a result of a locally high content of extracellular matrix molecules and/or cell adhesion molecules, factors which are not expressed in the region undergoing Wallerian degeneration.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J
J
Frisén
A
A
Haegerstrand
K
K
Fried
F
F
Piehl
S
S
Cullheim
M
M
Risling
D000818:Animals; D000906:Antibodies; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002448:Cell Adhesion; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000502:physiology*; D008297:Male; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
D000906:Antibodies; D015740:Calcitonin Gene-Related Peptide