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Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke.

Ruscher, Karsten LU ; Kuric, Enida LU ; Liu, Yawei LU ; Walter, Helene L ; Issazadeh, Shohreh LU ; Englund, Elisabet LU and Wieloch, Tadeusz LU (2013) In Journal of Cerebral Blood Flow and Metabolism 33(8). p.1225-1234
Abstract
After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after... (More)
After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3(+)) and CD3(+)/CD4(+) T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 May 2013; doi:10.1038/jcbfm.2013.71. (Less)
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Contribution to journal
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published
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in
Journal of Cerebral Blood Flow and Metabolism
volume
33
issue
8
pages
1225 - 1234
publisher
Nature Publishing Group
external identifiers
  • wos:000322570000012
  • pmid:23632969
  • scopus:84881121382
  • pmid:23632969
ISSN
1559-7016
DOI
10.1038/jcbfm.2013.71
language
English
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yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Neurosurgery (013026000)
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5b306d0f-26f0-4103-87a6-8e002a5d4af2 (old id 3805105)
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http://www.ncbi.nlm.nih.gov/pubmed/23632969?dopt=Abstract
date added to LUP
2016-04-01 09:54:56
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2020-10-04 03:07:49
@article{5b306d0f-26f0-4103-87a6-8e002a5d4af2,
  abstract     = {After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3(+)) and CD3(+)/CD4(+) T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 May 2013; doi:10.1038/jcbfm.2013.71.},
  author       = {Ruscher, Karsten and Kuric, Enida and Liu, Yawei and Walter, Helene L and Issazadeh, Shohreh and Englund, Elisabet and Wieloch, Tadeusz},
  issn         = {1559-7016},
  language     = {eng},
  number       = {8},
  pages        = {1225--1234},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke.},
  url          = {http://dx.doi.org/10.1038/jcbfm.2013.71},
  doi          = {10.1038/jcbfm.2013.71},
  volume       = {33},
  year         = {2013},
}