AXONAL AND NONNEURONAL CELL RESPONSES TO SPINAL-CORD INJURY IN MICE LACKING GLIAL FIBRILLARY ACIDIC PROTEIN

We have examined the regeneration of corticospinal tract fibers and ex pression of various extracellular matrix (ECM) molecules and intermedi ate filaments [vimentin and glial fibrillary acidic protein (GFAP)] af ter dorsal hemisection of the spinal cord of adult GFAP-null and wild- type littermate control mice. The expression of these molecules was al so examined in the uninjured spinal cord. There was no increase in axo n sprouting or long distance regeneration in GFAP-/-mice compared to t he wild type, in the uninjured spinal cord (i) GFAP was as expressed i n the wild type but not the mutant mice, while vimentin was expressed in astrocytes in the white matter of both types of mice; (ii) laminin and fibronectin immunoreactivity was localized to blood vessels and me ninges; (iii) tenascin and chondroitin sulfate proteoglycan (CSPG) lab eling was detected in astrocytes and the nodes of Ranvier in the white matter; and (iv) in addition, CSPG labeling which was generally less intense in the gray matter of mutant mice. Ten days after hemisection there was a large increase in vimentin(+) cells at the lesion site in both groups of mice. These include astrocytes as well as meningeal cel ls that migrate into the wound. The center of these lesions was filled by laminin(+)/fibronectin(+) cells, Discrete strands of tenascin-litr e immunoreactivity were seen in the core of the lesion and lining its walls, Marked increases in CSPG labeling was observed in the CNS paren chyma on either side of the lesion. These results indicate that the ab sence of GFAP in reactive astrocytes does not alter axonal, sprouting or regeneration. In addition, except for CSPG, the expression of vario us ECM molecules appears unaltered in GFAP-/-mice. (C) 1997 Academic P ress.