Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22468
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dc.contributor.advisorHENDRIX, Sven-
dc.contributor.advisorGOU FABREGAS, Myriam-
dc.contributor.authorMampay, Myrthe-
dc.date.accessioned2016-09-29T18:00:18Z-
dc.date.available2016-09-29T18:00:18Z-
dc.date.issued2016-
dc.identifier.urihttp://hdl.handle.net/1942/22468-
dc.description.abstractA disintegrin and metalloproteinase 17 (ADAM17) is responsible for shedding inflammatory mediators, such as TNF- and the phagocytic receptor CD36. Therefore, we hypothesize that inhibition of ADAM17 limits the production of pro-inflammatory cytokines and improves macrophage clearance of damaged tissue, leading to a better functional recovery after SCI.T-cut hemisection SCI was performed on ADAM17 hypomorphic (ADAM17ex/ex) and ADAM17 macrophage-specific knockout (ADAM17 M-KO) mice. Bone marrow-derived macrophages (BMDMs) were isolated from ADAM17ex/ex and ADAM17-overexpressing lentiviral particles were used to restore ADAM17 expression. ADAM17ex/ex mice showed an improved functional recovery after SCI and ADAM17ex/ex BMDMs produce reduced levels of sTNF-. Lentiviral-mediated overexpression of ADAM17 rescued the shedding of TNF- in ADAM17ex/ex BMDMs. ADAM17ex/ex macrophages show increased phagocytosis of spinal cord debris in vitro. However, no improvement in functional recovery was observed in ADAM17 M-KO mice compared to controls. These data indicate that ADAM17 affects functional recovery after SCI. Although ADAM17 limits BMDM phagocytic activity and stimulates sTNF- production, the observed improved functional recovery in ADAM17ex/ex mice was absent in ADAM17 M-KO mice. These results imply that the effect of ADAM17 in other phagocytic cell types, including microglia, are encouraged as they represent a promising therapeutic target to improve functional outcome after SCI.-
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dc.languagenl-
dc.publishertUL-
dc.titleA disintegrin and metalloproteinase 17 (ADAM17): an important factor to improve regeneration after CNS trauma-
dc.typeTheses and Dissertations-
local.bibliographicCitation.jcatT2-
dc.description.notesmaster in de biomedische wetenschappen-klinische moleculaire wetenschappen-
local.type.specifiedMaster thesis-
item.contributorMampay, Myrthe-
item.accessRightsOpen Access-
item.fullcitationMampay, Myrthe (2016) A disintegrin and metalloproteinase 17 (ADAM17): an important factor to improve regeneration after CNS trauma.-
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