title: Extracellular matrix alterations, accelerated leukocyte infiltration and enhanced axonal sprouting after spinal cord hemisection in tenascin-C-deficient mice.
abstract: The extracellular matrix glycoprotein tenascin-C has been implicated in wound repair and axonal growth. Its role in mammalian spinal cord injury is largely unknown. In vitro it can be both neurite-outgrowth promoting and repellent. To assess its effects on glial reactions, extracellular matrix formation, and axonal regrowth/sprouting in vivo, 20 tenascin-C-deficient and 20 wild type control mice underwent lumbar spinal cord hemisection. One, three, seven and fourteen days post-surgery, cryostat sections of the spinal cord were examined by conventional histology and by immunohistochemistry using antibodies against F4/80 (microglia/macrophage), GFAP (astroglia), neurofilament, fibronectin, laminin and collagen type IV. Fibronectin immunoreactivity was significantly down-regulated in tenascin-C-deficient mice. Moreover, fourteen days after injury, immunodensity of neurofilament-positive fibers was two orders of magnitude higher along the incision edges of tenascin-C-deficient mice as compared to control mice. In addition, lymphocyte infiltration was seen two days earlier in tenascin-C-deficient mice than in control mice and neutrophil infiltration was increased seven days after injury. The increase in thin neurofilament positive fibers in tenascin-C-deficient mice indicates that lack of tenascin-C alters the inflammatory reaction and extracellular matrix composition in a way that penetration of axonal fibers into spinal cord scar tissue may be facilitated.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Center for Experimental Medicine, Department of Anatomy and Experimental Morphology, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Schreiber
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Dietrich Ernst
authors.initials: DE
authors.lastname: Lorke
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013116:Spinal Cord / Q000601:surgery*; D019063:Tenascin / Q000172:deficiency* / Q000378:metabolism
chemical_list: D019063:Tenascin; C477504:tenascin-N protein, mouse
keywords: Astrocytes; CNS; CST; Collagen; ECM; Fibronectin; GFAP; H&E; IOD; Laminin; Microglia; Mouse; NF; Neurofilament; PBS; PFA; TNC; TNC+/+; TNC−/−; U; arbitrary unit; central nervous system; corticospinal tract; extracellular matrix; glial fibrillary acidic protein; hematoxylin and eosin; integrated optical density; neurofilament; paraformaldehyde; phosphate buffered saline; tenascin-C; tenascin-C wild type; tenascin-C-deficient