Universität zu Köln

Walter, Helene L., van der Maten, Gerlinde, Antunes, Ana Rita, Wieloch, Tadeusz ORCID: 0000-0002-7669-2520 and Ruscher, Karsten (2015). Treatment with AMD3100 attenuates the microglial response and improves outcome after experimental stroke. J. Neuroinflamm., 12. LONDON: BMC. ISSN 1742-2094

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Abstract

Background: Recovery of lost neurological function after stroke is limited and dependent on multiple mechanisms including inflammatory processes. Selective pharmacological modulation of inflammation might be a promising approach to improve stroke outcome. Methods: We used 1,1'-[1,4-phenylenebis(methylene)] bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and potential allosteric agonist to CXCR7, administered to mice twice daily from day 2 after induction of photothrombosis (PT). In addition to functional outcome, the dynamics of post-stroke microglia response were monitored in vivo by 2-photon-laser-microscopy in heterozygous transgenic CX(3)CR1-green fluorescent protein (GFP) mice (CX(3)CR1(GFP/+)) and complemented with analyses for fractalkine (FKN) and pro-inflammatory cytokines. Results: We found a significantly enhanced recovery and modified microglia activation without affecting infarct size in mice treated with AMD3100 after PT. AMD3100 treatment significantly reduced the number of microglia in the peri-infarct area accompanied by stabilization of soma size and ramified cell morphology. Within the ischemic infarct core of AMD3100 treated wild-type mice we obtained significantly reduced levels of the endogenous CX(3)CR1 ligand FKN and the pro-inflammatory cytokines interleukin (IL)-1 beta and IL-6. Interestingly, in CX(3)CR1-deficient mice (homozygous transgenic CX(3)CR1-GFP mice) subjected to PT, the levels of FKN were significantly lower compared to their wild-type littermates. Moreover, AMD3100 treatment did not induce any relevant changes of cytokine levels in CX(3)CR1 deficient mice. Conclusion: After AMD3100 treatment, attenuation of microglia activation contributes to enhanced recovery of lost neurological function in experimental stroke possibly due to a depression of FKN levels in the brain. We further hypothesize that this mechanism is dependent on a functional receptor CX(3)CR1.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walter, Helene L. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Maten, Gerlinde UNSPECIFIED UNSPECIFIED UNSPECIFIED Antunes, Ana Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieloch, Tadeusz UNSPECIFIED orcid.org/0000-0002-7669-2520 UNSPECIFIED Ruscher, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-412602
DOI:	10.1186/s12974-014-0232-1
Journal or Publication Title:	J. Neuroinflamm.
Volume:	12
Date:	2015
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1742-2094
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL CEREBRAL-ISCHEMIA; FRACTALKINE-RECEPTOR; FUNCTIONAL RECOVERY; BRAIN INFLAMMATION; MOUSE-BRAIN; NEURONS; CHEMOKINE; CX(3)CR1; EXPRESSION; INHIBITION Multiple languages Immunology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41260