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

Paula M. Hughes, Peter R. Allegrini, Markus Rudin, V. Hugh Perry, Anis K. Mir, Christoph Wiessner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

270 Citations (SciVal)

Abstract

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.
Original languageEnglish
Pages (from-to)308-317
Number of pages10
JournalJournal of Cerebral Blood Flow & Metabolism
Volume22
Issue number3
DOIs
Publication statusPublished - 01 Mar 2002
Externally publishedYes

Keywords

  • Astrocytes
  • Chemokines
  • Cytokines
  • Focal cerebral ischemia
  • MCP-1
  • Microglia
  • Neuroinflammation
  • Blood Pressure
  • Cerebral Infarction/pathology
  • Mice, Inbred C57BL
  • Reference Values
  • Middle Cerebral Artery
  • Mice, Knockout
  • Magnetic Resonance Imaging
  • Chemokine CCL2/deficiency
  • Animals
  • Stroke/pathology
  • Cerebrovascular Circulation/physiology
  • Thalamus/pathology
  • Mice
  • Crosses, Genetic

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