We recognized for the first time upregulation of type VIII collagen gene expression during the repair process in the mouse brain cold injury model. Immunohistochemical staining showed that type VIII collagen expression was around the necrotic region, where reactive astrocytes are frequently observed. Cultured astrocytes demonstrated a high expression of type VIII collagen genes. TGF-beta1 enhanced the expression of both alpha1(VIII) and alpha2(VIII) genes by astrocytes in culture. Further, we tested selected biological activities of type VIII collagen, compared with those of type I, IV, and V collagens and fibronectin. Astrocytes adhered to type VIII collagen via receptors requiring metal ions. Astrocyte migration on type VIII collagen was more stimulated than that observed on the other ECM molecules. These data indicate that type VIII collagen plays an important role in glial scar formation during the repair process by astrocytes. (C) 2004 Elsevier Inc. All rights reserved.