Tenascin is an extracellular matrix molecule synthesized and released by young astrocytes during embryonic and early postnatal development of the nervous system, and it is concentrated in boundaries around emerging functional neuronal units. In the adult nervous system, tenascin can be detected only in very low levels. Distinct spatial and temporal distributions of tenascin during developmental events suggest a role in the guidance and/or segregation of neurons and their processes within incipient functional patterns. We show here, using in situ hybridization and immunocytochemistry, that stab wounds of the adult mouse cerebellar and cerebral cortices result in an enhanced expression of tenascin in a discrete region around the lesion site that is associated with a subset of glial fibrillary acidic protein-positive astrocytes. Tenascin upregulation in the lesioned adult brain may be directly involved in failed regeneration or indirectly involved through its interactions with other glycoconjugates that either inhibit or facilitate neurite growth.Extracellular matrix (ECM) molecules may have important roles during embryonic development, possibly acting as permissive substrates that help guide cells and their processes to their targets (1). Other types of ECM molecules that have only recently been described in the central nervous system (CNS) [e.g., sulfated proteoglycans (2)] could have inhibitory functions and form barriers to growth.The tenascin molecule is an oligomeric glycoprotein constituent of the ECM that carries the carbohydrate epitope characteristic ofthe L2/HNK-1 family ofadhesion molecules (3, 4). It is referred to variously (3) as hexabrachion, glioma mesenchymal extracellular matrix protein, J1, or cytotactin. In the developing CNS, tenascin is synthesized and expressed by young astrocytes possibly mediating certain neuron-glia interactions (5). Even though the molecule is widely distributed in many different tissues during development and hyperplasia (e.g., in cartilage, regions of epithelialmesenchymal interactions, tumors) (3), in the CNS it exhibits site-restricted expression (6,7). This latter attribute of tenascin distribution prompted the designation of these regions as "boundaries," where dense accumulations of this and other glycoconjugates (i.e., glycoproteins, glycolipids, or glycosaminoglycans) cordon off emerging neuronal arrays (8). The possible biological actions of tenascin have been assayed in culture paradigms using neural (e.g., neural crest, neurons, and astrocytes) and nonneural (e.g., fibroblasts) cells, with evidence for inhibition and promotion of migration and process outgrowth (9)(10)(11)(12).The presence or absence of tenascin in or around lesion sites may have important implications for the sequelae of CNS injury. Here, we examine the effects of cerebellar and cerebral cortical lesions on tenascin expression in the adult mouse. The current study presents in situ hybridization and immunocytochemical data showing an enhanced expression of astrocytic tenascin associat...