CHEMOKINE MONOCYTE CHEMOATTRACTANT PROTEIN-1 IS EXPRESSED BY ASTROCYTES AFTER MECHANICAL INJURY TO THE BRAIN

By 24 h after mechanical trauma to the cerebral cortex, astroglial rea ction begins and injury sites are infiltrated by activated mononuclear phagocytes derived from blood-borne monocytes and endogenous microgli a, There is little information about cellular interactions between ast rocytes and leukocytes during this process, We previously showed that murine astrocytes produce chemokines including monocyte chemoattractan t protein-1 (MCP-1) during experimental autoimmune encephalomyelitis, In this study, we asked whether astrocytes produce MCP-1 in the absenc e of immune mediated inflammation, To address this question, we analyz ed the time course and cellular source of MCP-1 in mouse brain after p enetrating mechanical injury, with particular focus on early time poin ts before histologic detection of infiltrating mononuclear phagocytes, We observed sharply increased steady state levels of MCP-1 mRNA withi n 3 h after nitrocellulose membrane stab or implant injury to the adul t mouse brain, and MCP-1 protein elevations were documented at 12 h po stinjury, In situ hybridization combined with immunohistochemistry for the glial fibrillary acidic protein astrocyte marker showed that astr ocytes were the cellular source of MCP-1 mRNA at these early time poin ts after mechanical brain injury, Stab injury to the neonatal brain ev oked neither MCP-1 expression nor astrogliosis, These results demonstr ate that chemokine gene expression comprises one component of the astr ocyte activation program. The data are consistent with a role for MCP- 1 in the central nervous system inflammatory response to trauma.