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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3805105
- author
- Ruscher, Karsten
LU
; Kuric, Enida
LU
; Liu, Yawei
LU
; Walter, Helene L
; Issazadeh, Shohreh
LU
; Englund, Elisabet
LU
and Wieloch, Tadeusz
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- LU publication?
- yes
- additional info
- 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)
- id
- 5b306d0f-26f0-4103-87a6-8e002a5d4af2 (old id 3805105)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23632969?dopt=Abstract
- date added to LUP
- 2016-04-01 09:54:56
- date last changed
- 2022-05-05 08:52:37
@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}},
}