Monocyte Chemoattractant Protein-1 Deficiency is Protective in a Murine Stroke Model

• Paula M. Hughes

  Nurin Ltd., CNS Inflammation, University of Southampton, Biomedical Science Building, Southampton

• Peter R. Allegrini

  Core Technology Area, Novartis Pharma AG, Basel, Switzerland

• Markus Rudin

  Core Technology Area, Novartis Pharma AG, Basel, Switzerland

• V. Hugh Perry

  CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton, U.K.

• Anis K. Mir

  Nervous System Research

• Christoph Wiessner

  Nervous System Research

抄録

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-1β 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.

収録刊行物

• Journal of Cerebral Blood Flow & Metabolism

  Journal of Cerebral Blood Flow & Metabolism 22 (3), 308-317, 2002-03

  SAGE Publications

キーワード

• Cardiology and Cardiovascular Medicine
• Neurology (clinical)
• Neurology

詳細情報

• CRID: 1363951794919186816
• NII論文ID: 30009335592
• DOI: 10.1097/00004647-200203000-00008
• ISSN: 15597016
• ISSN: 0271678X
• Web Site: http://journals.sagepub.com/doi/pdf/10.1097/00004647-200203000-00008
• Web Site: http://journals.sagepub.com/doi/full-xml/10.1097/00004647-200203000-00008
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