Notice that the concentration of the AMP1 immunoreactivity at regions of cellCcell contact is similar to that observed for N-CAM
Notice that the concentration of the AMP1 immunoreactivity at regions of cellCcell contact is similar to that observed for N-CAM. as rTAPA). rTAPA is usually a member of the tetramembrane-spanning superfamily of proteins and, as with other members of this family of proteins, rTAPA is associated with the regulation of cellular interactions and mitotic activity. After an injury to the cerebral cortex, there is a dramatic increase in AMP1 immunoreactivity that is spatially restricted to the reactive astrocytes at the glial scar. This change represents an upregulation of a membrane protein, rTAPA, that is approximately equal to the increase observed for glial fibrillary acidic protein. The high levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation studies indicate that rTAPA may play a prominent role in the response of astrocytes to injury and in glial scar formation. Keywords: astrocyte, regeneration, cell adhesion, brain, reactive gliosis, injury, rat, TAPA, actinin After traumatic injury to the brain or spinal cord, a complex series of cellular responses occurs as the CNS attempts to heal itself. In many cases, one consequence of this process is usually a loss of neural function associated with damaged axonal pathways. This lack of functional regeneration Ntn1 appears to be attributable to multiple factors. As glial cells mature, there is a reduction in the expression of molecules known to promote axonal outgrowth (Smith et al., 1993). Furthermore, several molecules have been identified in the adult mammalian CNS that block or inhibit axonal growth (Caroni and Schwab, 1988; McKeon et al., 1991; Geisert and Bidanset, 1993; McKerracher et al., 1994; Mukhopadhyay et al., 1994). In addition, local factors unique to the site of injury also may Pravadoline (WIN 48098) play a role in the lack of axonal regrowth. In the immediate vicinity of the injury, astrocytes become reactive, dramatically elevating the levels of cytoskeletal elements, membrane proteins, and extracellular matrix components (Eng et al., 1971;Bignami and Dahl, 1976; Liesi and Sliver, 1988; Geisert et al., 1990;Rudge and Silver, 1990; Laywell et al., 1992; Le Gal La Salle et al., 1992). As with other healing processes, the reactive astrocytes are believed to reestablish a protective barrier, the glial limiting membrane (Reier, 1986). However, in the injured CNS, Pravadoline (WIN 48098) this barrier, a gliotic scar, is located deep within the parenchyma of the brain or spinal cord. This glial scar and its immediate environment are believed to contribute to the lack of functional axonal regeneration (Reier and Houle, 1988). The glial scar may represent a physical barrier in that it disrupts continuity of previously established axonal pathways. In addition, the molecules expressed by the reactive astrocytes may represent a molecular barrier to regenerating axons (Geisert and Stewart, 1991; McKeon et al., 1991; Laywell et al., 1992). An examination of the glial scar at the light and electron microscopic levels reveals that this astrocytic processes appear to recognize each other, running in parallel arrays to form a scar. Defining the molecules that regulate astrocyte interactions during scar formation is critical to an understanding of the role of the glial scar in CNS wound healing and its potential contribution to the lack of axonal regeneration after injury. One approach to defining the molecules regulating glial scar formation is to use cultured astrocytes as a model system. We reasoned that antibodies recognizing cell surface molecules regulating astrocyte growth might alter the function of these molecules. The antibodies then could be used to isolate and characterize membrane proteins involved in regulating astrocyte interactions during scar formation. This approach led to the monoclonal antibody AMP1, which modulates cellular interactions between astrocytes (Geisert Pravadoline (WIN 48098) et al., 1991). This antibody recognizes an astrocytic membrane protein called Target of the Anti-Proliferative Antibody (TAPA), which after injury is upregulated to the same extent as glial fibrillary acidic protein (GFAP) and which plays a role.