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-1-/-) 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 infarcts 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-1-/- 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 infarct size after stroke.
Hughes
Paula M
PM
Nervous System Research, Core Technology Area, Novartis Pharma AG, Basel, Switzerland.
Allegrini
Peter R
PR
Rudin
Markus
M
Perry
V Hugh
VH
Mir
Anis K
AK
Wiessner
Christoph
C
D000818:Animals; D001794:Blood Pressure; D002544:Cerebral Infarction / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003433:Crosses, Genetic; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020768:Middle Cerebral Artery; D012016:Reference Values; D020521:Stroke / Q000473:pathology / Q000517:prevention & control*; D013788:Thalamus / Q000473:pathology
D018932:Chemokine CCL2