EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND MACROPHAGE INFLAMMATORY PROTEIN-1 AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

Chemoattractant cytokines, the chemokines, play an important role in e arly events of inflammation at the site of tissue damage. We examined the expression of mRNA and the protein products of two such chemokines ; i.e. monocyte chemoattractant protein-1 (MCP-1) and macrophage infla mmatory protein-1 alpha (MIP-1 alpha) in the ischemic brain tissue fol lowing middle cerebral artery occlusion (MCAo). The mRNA transcripts o f MCP-1 and MIP-1 alpha were detected by Northern hybridization and re verse transcriptase polymerase chain reaction (RT/PCR), respectively, and the anatomic distribution of specific proteins was analyzed by imm unohistochemistry. We found that MCP-1 mRNA was not expressed in the b rains of normal rats or rats sacrificed 2 h after MCAo. 6 h after the induction of cerebral ischemia, weak expression of both mRNAs was dete cted in the ischemic tissue. mRNAs were expressed up to 48 h, and were markedly attenuated at 96 h. In the rats subjected to MCA occlusion, MCP-1 immunoreactivity was diffusely expressed and localized to the is chemic area, and was most intense at 48 h after MCA occlusion. Endothe lial cells and macrophage-like cells expressed MCP-1 protein in the is chemic brain. The distribution and morphology of MIP-1 alpha immunorea ctive cells were identical with activated astrocytes. We conclude that MCP-1 and MIP-1 alpha mRNAs and proteins are induced after cerebral i schemia in the rat. They may have a role in promoting inflammatory and /or repair processes in the ischemic brain, possibly by attracting or modulating inflammatory cells in the ischemic area.