Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats

Chemokines have been shown to play an important role in leukocyte infiltrat ion into ischemic lesions. Recently, the increased expression of monocyte c hemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemo attr actant (CINC) Tvas observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein lev el and time course of these chemokines have not been fully elucidated. Ther efore, we analyzed the time-dependent production of MCP-1 and CINC iu the r at brain after transient middle cerebral artery occlusion (MCAO) by means o f specific enzyme-linked immunosorbent assay systems, The MCP-1 levels in t he ipsilateral hemispheres increased from 6 h, peaked at 2 days, and therea fter gradually decreased. The peak MCP-1 concentration tvas 89.2 +/- 28.2 n g/g tissue wet weight (mean +/- SEM, n = 5, 49.3-fold greater than the cont ralateral value at the same time, P < 0.05), which is supposed to be high e nough to exert its biological effects. In contrast, the maximum CINC concen tration that corresponded to 2.9 +/- 0.7 ng/g tissue wet weight (mean +/- S EM, n = 5, 55.0-fold greater than the contralateral value at the same time, P < 0.05), Tvas observed at 6 h, In addition, we confirmed the temporal pr ofile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1-3 days), followed by m assive infiltration of macrophages at later stages (2-7 days). These studie s suggest that MCP-1 iu cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of in filtrated leukocyte subtypes.