Connective tissue growth factor is expressed by a subset of reactive astrocytes in human cerebral infarction

Connective tissue growth factor (CTGF), a transforming growth factor (TGF)- beta(1) downstream mediator, is a secreted cell matrix-inducing peptide inv olved in both tissue regeneration mechanisms, such as wound repair, and als o in aberrant deposition of extracellular matrix. The present study reports CTGF expression by cells associated with matrix deposition and glial scar formation in human cerebral infarction. CTGF was localized by immunohistoch emistry in 17 brains of patients after focal infarction and in three neurop athologically normal control brains. CTGF expression was selectively locali zed to the cytoplasm of stellate reactive astrocytes. Compared to periphera l areas and brain controls without neuropathological findings, the total nu mber CTGF(+) astrocytes was significantly higher (P < 0.0001) in border zon es adjacent to the core, corresponding to the penumbra. These numbers were significantly increased at day 1 and day 3 and remained persistently elevat ed up to several months post-infarction (P < 0.0001). The restricted expres sion and accumulation of CTGF(+) reactive astrocytes adds convincing eviden ce for CTGF participation in the gliotic astrocyte CNS injury response invo lved in glial scar formation. CTGF can be considered a sensitive marker of early human astrocyte activation and a possible target for pharmacological intervention of aberrant matrix deposition.