Role of endothelin-1 in astrocyte responses after acute brain damage.

We examined the possibility of the involvement of endothelin (ET)-1, a potent vasoactive peptide, in the process of astrocyte proliferation after brain injury. Acute brain damage in rats was induced by cold-injury. Astrocytes changed from a differentiated state to an immature, RC-1-positive state immediately after the injury. In the injured site, the level of ET-1-like immunoreactivity in the tissue was significantly increased on the first postoperative day and was sustained at a high level for 5 days. ET(B) receptor mRNA was markedly but transiently down-regulated only on the first day after the injury. Brain extracts (BE) were prepared from the injured tissues, and their effects on the proliferative characteristics of astrocytes were examined in primary culture of astrocytes. The flat morphology, which was observed in association with cell proliferation, and DNA synthesis of astrocytes were enhanced by treatment with each of the BE from 1 (D1-BE), 3 and 5 days after the injury. A monoclonal antibody that recognizes the C-terminus of rat ET-1 and ET-3 inhibited the DNA synthesis of astrocytes induced by D1-BE. These results provide experimental evidence that ET-1 may participate in the initiation of gliosis in the acute phase of brain damage.