ACUTE EXPOSURE TO CNTF IN-VIVO INDUCES MULTIPLE COMPONENTS OF REACTIVE GLIOSIS

CNS trauma or disease induces a constellation of changes in the glia c omprising the condition known as reactive gliosis, At present, little is known regarding the nature of the injury signals and the specific c onsequences of their actions. Ciliary neurotrophic factor (CNTF) induc es acute phase proteins in liver and increases astrocytic glial fibril lary acidic protein (GFAP) both in vitro and in vivo. The purpose of t he present study was to establish whether CNTF induces other aspects o f gliosis. Between 10 and 72 h after 100 ng of recombinant human CNTF was administered into the adult rat neocortex, alterations were observ ed in a region extending several millimeters in circumference from the injection site. Microglia in this region were more apparent and astro cytes were hypertrophic. By in situ hybridization, mRNAs for GFAP, vim entin, and clusterin were upregulated when compared to the control hem isphere (which received heat-inactivated CNTF). By immunocytochemistry , GFAP, vimentin, glutathione-S-transferase mu, S-100, and OX-42 were elevated by 48 h. By contrast, the oligodendroglial marker GST Yp, the neuronal markers MAP-2 and NSE, the intermediate filament nestin, and the stress protein alpha B-crystallin were unchanged. In addition, a greater than twofold increase in the number of proliferating cells was observed. Since CNTF induces swelling and multiple ''gliotic'' genes in astrocytes, increases microglial number, and stimulates cell prolif eration, we conclude that CNTF is sufficient to induce multiple aspect s of gliosis. These data are consistent with a model whereby CNTF (whi ch is synthesized by astrocytes) would be released when the integrity of the astrocyte membrane is compromised, whereupon it would elicit an inflammatory response. (C) 1996 Academic Press, Inc.