CNS
trauma or disease induces a constellation of changes in the glia comprising the condition known as reactive
gliosis. At present, little is known regarding the nature of the injury signals and the specific consequences of their actions.
Ciliary neurotrophic factor (
CNTF) induces
acute phase proteins in liver and increases astrocytic
glial fibrillary acidic protein (GFAP) both in vitro and in vivo. The purpose of the present study was to establish whether
CNTF induces other aspects of
gliosis. Between 10 and 72 h after 100 ng of recombinant human
CNTF was administered into the adult rat neocortex, alterations were observed in a region extending several millimeters in circumference from the injection site. Microglia in this region were more apparent and astrocytes were hypertrophic. By in situ hybridization, mRNAs for GFAP,
vimentin, and
clusterin were upregulated when compared to the control hemisphere (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 GSTYp, 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 proliferation, we conclude that
CNTF is sufficient to induce multiple aspects of
gliosis. These data are consistent with a model whereby
CNTF (which is synthesized by astrocytes) would be released when the integrity of the astrocyte membrane is compromised, whereupon it would elicit an inflammatory response.