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Sökning: WFRF:(Degn Matilda) > (2016) > Conditional ablatio...

  • Clausen, Bettina HjelmUniversity of Southern Denmark (författare)

Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-07-07
  • Springer Science and Business Media LLC,2016

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:faf81412-47bc-4956-83c0-8645bd716430
  • https://lup.lub.lu.se/record/faf81412-47bc-4956-83c0-8645bd716430URI
  • https://doi.org/10.1038/srep29291DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Microglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNF fl/fl) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ∼93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naïve LysMcreTNF fl/fl mice demonstrating altered ERK signal transduction. Micro-PET using 18 [F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNF fl/fl mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNF fl/fl mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNF fl/fl mice compared to littermate mice, whereas no TNF + leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNF fl/fl mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Degn, MatildaCopenhagen University Hospital (författare)
  • Sivasaravanaparan, MithulaUniversity of Southern Denmark (författare)
  • Fogtmann, TorbenUniversity of Southern Denmark (författare)
  • Andersen, Maria GammelstrupUniversity of Southern Denmark (författare)
  • Trojanowsky, Michelle D.University of Miami (författare)
  • Gao, HanUniversity of Miami (författare)
  • Hvidsten, SvendOdense University Hospital (författare)
  • Baun, ChristinaOdense University Hospital (författare)
  • Deierborg, TomasLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)expb-tol (författare)
  • Finsen, BenteUniversity of Southern Denmark (författare)
  • Kristensen, Bjarne WintherOdense University Hospital,University of Southern Denmark (författare)
  • Bak, Sara ThornbyUniversity of Southern Denmark (författare)
  • Meyer, MortenUniversity of Southern Denmark (författare)
  • Lee, JaeUniversity of Miami (författare)
  • Nedospasov, Sergei A.P.N. Lebedev Physical Institute of the Russian Academy of Sciences,Lomonosov Moscow State University (författare)
  • Brambilla, RobertaUniversity of Miami (författare)
  • Lambertsen, Kate LykkeUniversity of Southern Denmark,Odense University Hospital (författare)
  • University of Southern DenmarkCopenhagen University Hospital (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Scientific Reports: Springer Science and Business Media LLC62045-2322

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