Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model

Inflammatory processes have been implicated in the pathogenesis of brain damage after stroke. In rodent stroke models, focal ischemia induces several proinflammatory chemokines. including monocyte chemoattractant protein-1 (MCP-1) The individual contribution to ischemic tissue damage, however, is largely unknown. To address this question, the authors subjected MCP-1-deficient mice (MCP-l(-/-)) to permanent middle cerebral artery occlusion (MCAO). Measurement of basal blood pressure, cerebral blood flow, and blood volume revealed no differences between wild-type (wt) and MCP-1(-/-) mice. MCAO led to similar cerebral perfusion deficits in wt and MCP-1(-/-) mice, excluding differences in the MCA supply territory and collaterals. However, compared with wt mice, the mean infarct volume was 29% smaller in MCP-1(-/-) mice 24 hours after MCAO (P = 0.022). Immunostaining showed a reduction of phagocytic macrophage accumulation within infarets and the infarct border in MCP-1(-/-) mice 2 weeks after MCAO. At the same time point, the authors found an attenuation of astrocytic hypertrophy in the infarct border and thalamus in MCP-1(-/-) mice. However, these effects on macrophages and astrocytes in MCP-l(-/-) mice occurred too late to suggest a protective role in acute infarct growth. Of note: at 6 hours after MCAO, MCP-1(-/-) mice produced significantly less interleukin-1beta in ischemic tissue: this might be related to tissue protection. The results of this study indicate that inhibition of MCP-1 signaling could be a new acute treatment approach to limit infaret size after stroke.