Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model
Hughes, Paula M., Allegrini, Peter R., Rudin, Markus, Perry, V. Hugh, Mir, Anis K. and Wiessner, Christoph (2002) Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. Journal of Cerebral Blood Flow & Metabolism, 22, (3), 308-317. (doi:10.1097/00004647-200203000-00008).
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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.
|Keywords:||MCP-1, chemokines, cytokines, neuroinflammation, focal cerebral ischemia, astrocytes, microglia|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
|Date Deposited:||07 Aug 2008|
|Last Modified:||11 Jun 2013 01:46|
|Contributors:||Hughes, Paula M. (Author)
Allegrini, Peter R. (Author)
Rudin, Markus (Author)
Perry, V. Hugh (Author)
Mir, Anis K. (Author)
Wiessner, Christoph (Author)
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