ACTIVATED MACROPHAGES AND THE BLOOD-BRAIN-BARRIER - INFLAMMATION AFTER CNS INJURY LEADS TO INCREASES IN PUTATIVE INHIBITORY MOLECULES

The cellular responses to spinal cord or brain injury include the prod uction of molecules that modulate wound healing. This study examined t he upregulation of chondroitin sulfate proteoglycans, a family of mole cules present in the wound healing matrix that may inhibit axon regene ration in the central nervous system (CNS) after trauma. We have demon strated increases in these putative inhibitory molecules in brain and spinal cord injury models, and we observed a close correlation between the tissue distribution of their upregulation and the presence of inf lammation and a compromised blood-brain barrier. We determined that th e presence of degenerating and dying axons injured by direct trauma do es not provide a sufficient signal to induce the increases in proteogl ycans observed after injury. Activated macrophages, their products, or other serum components that cross a compromised blood-brain barrier m ay provide a stimulus for changes in extracellular matrix molecules af ter CNS injury. While gliosis is associated with increased levels of p roteoglycans, not all reactive astrocytes are associated with augmente d amounts of these extracellular matrix molecules, which suggests a he terogeneity among glial cells that exhibit a reactive phenotype. Chond roitin sulfate also demarcates developing cavities of secondary necros is, implicating these types of boundary molecules in the protective re sponse of the CNS to trauma. (C) 1997 Academic Press.