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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Description/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-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.
| Item Type: | Article |
|---|---|
| ISSNs: | 0271-678X (print) |
| Related URLs: | |
| 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 |
| Item ID: | 56503 |
| 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) |
| Date: | March 2002 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/56503 |
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