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 early 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 inflammatory protein-1 alpha (MIP-1 alpha) in the ischemic brain tissue following middle cerebral artery occlusion (MCAo). The mRNA transcripts of MCP-1 and MIP-1 alpha were detected by Northern hybridization and reverse transcriptase polymerase chain reaction (RT/PCR), respectively, and the anatomic distribution of specific proteins was analyzed by immunohistochemistry. We found that MCP-1 mRNA was not expressed in the brains of normal rats or rats sacrificed 2 h after MCAo. 6 h after the induction of cerebral ischemia, weak expression of both mRNAs was detected 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 ischemic area, and was most intense at 48 h after MCA occlusion. Endothelial cells and macrophage-like cells expressed MCP-1 protein in the ischemic brain. The distribution and morphology of MIP-1 alpha immunoreactive cells were identical with activated astrocytes. We conclude that MCP-1 and MIP-1 alpha mRNAs and proteins are induced after cerebral ischemia 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.