| Following injury to the central nervous system, the elevation in the levels of various cytokines is believed to act upon both native and recruited cells to alter their physical and biochemical properties. These changes in astrocyte physiology may be responsible for failed axonal regeneration through the creation of a glial scar which displays altered levels of extracellular matrix (ECM) molecules. Cytokines both singularly and in combination were able to uniquely alter the levels of the ECM molecules: tenascin, laminin, fibronectin, thrombospondin, and chondroitin sulfate proteoglycans of astrocyte cultures as examined by Western blotting. The alteration of fibronectin levels by cytokines may be through a novel, cell-specific transcriptional element within the promoter as demonstrated by electrophoretic mobility shift assays. In addition, cytokine-treated astrocyte monolayers differentially supported neurite extension which could be modulated by neutralizing antibodies to tenascin, suggesting that ECM molecules are integral to regulating axonal growth after injury.; Cytokines regulate the synthesis of the enzyme inducible nitric oxide sythase (iNOS) in multiple cells types. Once synthesized iNOS can tonically release cytotoxic levels of nitric oxide. Western blotting revealed iNOS present within 48 hours that persisted for at least 7 days following a spinal cord crush injury. Immunohistochemistry of spinal cord tissue after 3 days post-trauma demonstrates that iNOS reactivity co-localizes with macrophages along the borders of the lesion and with neurons and glia distal from the injury. Three weeks post-trauma, iNOS is still present and co-localizes with macrophages bordering areas of developing cavitation. Thus, iNOS may contribute to tissue necrosis and pharmacological treatments designed to inhibit iNOS may help attenuate overall tissue damage.; A single application of a suramin, a cytokine inhibitor, to a stab wound injury of the adult rat brain transiently attenuated various aspects of gliosis, including upregulation of glial fibrillary acidic protein, cell proliferation, and tenascin immunoreactivity. In addition, examination of the corpus callosum of saline-treated animals 30 days post-trauma revealed a disruption of the fiber tract within the lesion site, while suramin-treated animals displayed numerous fibers spanning the lesion. These results demonstrate that transient inhibition of cytokine activity may be sufficient to ameliorate subsequent tissue damage. |
