000273922 001__ 273922
000273922 005__ 20241215000113.0
000273922 0247_ $$2doi$$a10.3389/fimmu.2024.1443940
000273922 0247_ $$2pmid$$apmid:39635532
000273922 0247_ $$2pmc$$apmc:PMC11614719
000273922 0247_ $$2altmetric$$aaltmetric:170930407
000273922 037__ $$aDZNE-2024-01396
000273922 041__ $$aEnglish
000273922 082__ $$a610
000273922 1001_ $$aRehman, Rida$$b0
000273922 245__ $$aThe FGFR inhibitor Rogaratinib reduces microglia reactivity and synaptic loss in TBI.
000273922 260__ $$aLausanne$$bFrontiers Media$$c2024
000273922 3367_ $$2DRIVER$$aarticle
000273922 3367_ $$2DataCite$$aOutput Types/Journal article
000273922 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1733823757_31710
000273922 3367_ $$2BibTeX$$aARTICLE
000273922 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000273922 3367_ $$00$$2EndNote$$aJournal Article
000273922 520__ $$aTraumatic brain injury (TBI) induces an acute reactive state of microglia, which contribute to secondary injury processes through phagocytic activity and release of cytokines. Several receptor tyrosine kinases (RTK) are activated in microglia upon TBI, and their blockade may reduce the acute inflammation and decrease the secondary loss of neurons; thus, RTKs are potential therapeutic targets. We have previously demonstrated that several members of the Fibroblast Growth Factor Receptor (FGFR) family are transiently phosporylated upon TBI; the availability for drug repurposing of FGFR inhibitors makes worthwhile the elucidation of the role of FGFR in the acute phases of the response to TBI and the effect of FGFR inhibition.A closed, blunt, weight-drop mild TBI protocol was employed. The pan-FGFR inhibitor Rogaratinib was administered to mice 30min after the TBI and daily up to 7 days post injury. Phosphor-RTK Arrays and proteomic antibody arrays were used to determine target engagement and large-scale impact of the FGFR inhibitor. pFGFR1 and pFGFR3 immunostaining were employed for validation. As outcome parameters of the TBI injury immunostainings for NeuN, VGLUT1, VGAT at 7dpi were considered.Inhibition of FGFR during TBI restricted phosphorylation of FGFR1, FGFR3, FGFR4 and ErbB4. Phosphorylation of FGFR1 and FGFR3 during TBI was traced back to Iba1+ microglia. Rogaratinib substantially dowregulated the proteomic signature of the neuroimmunological response to trauma, including the expression of CD40L, CXCR3, CCL4, CCR4, ILR6, MMP3 and OPG. Prolonged Rogaratinib treatment reduced neuronal loss upon TBI and prevented the loss of excitatory (vGLUT+) synapses.The FGFR family is involved in the early induction of reactive microglia in TBI. FGFR inhibition selectively prevented FGFR phosphorylation in the microglia, dampened the overall neuroimmunological response and enhanced the preservation of neuronal and synaptic integrity. Thus, FGFR inhibitors may be relevant targets for drug repurposing aimed at modulating microglial reactivity in TBI.
000273922 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000273922 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000273922 650_7 $$2Other$$aproteomics
000273922 650_7 $$2Other$$areactive microglia
000273922 650_7 $$2Other$$areceptor tyrosine kinase
000273922 650_7 $$2Other$$asynapses
000273922 650_7 $$2Other$$atraumatic brain injury
000273922 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, Fibroblast Growth Factor, Type 1
000273922 650_7 $$2NLM Chemicals$$aProtein Kinase Inhibitors
000273922 650_2 $$2MeSH$$aAnimals
000273922 650_2 $$2MeSH$$aMicroglia: drug effects
000273922 650_2 $$2MeSH$$aMicroglia: metabolism
000273922 650_2 $$2MeSH$$aBrain Injuries, Traumatic: drug therapy
000273922 650_2 $$2MeSH$$aBrain Injuries, Traumatic: metabolism
000273922 650_2 $$2MeSH$$aBrain Injuries, Traumatic: immunology
000273922 650_2 $$2MeSH$$aMice
000273922 650_2 $$2MeSH$$aMale
000273922 650_2 $$2MeSH$$aSynapses: drug effects
000273922 650_2 $$2MeSH$$aSynapses: metabolism
000273922 650_2 $$2MeSH$$aMice, Inbred C57BL
000273922 650_2 $$2MeSH$$aPhosphorylation: drug effects
000273922 650_2 $$2MeSH$$aDisease Models, Animal
000273922 650_2 $$2MeSH$$aReceptor, Fibroblast Growth Factor, Type 1: antagonists & inhibitors
000273922 650_2 $$2MeSH$$aReceptor, Fibroblast Growth Factor, Type 1: metabolism
000273922 650_2 $$2MeSH$$aProtein Kinase Inhibitors: pharmacology
000273922 650_2 $$2MeSH$$aProtein Kinase Inhibitors: therapeutic use
000273922 7001_ $$aFroehlich, Albrecht$$b1
000273922 7001_ $$aOlde Heuvel, Florian$$b2
000273922 7001_ $$aElsayed, Lobna$$b3
000273922 7001_ $$0P:(DE-2719)2812855$$aBoeckers, Tobias$$b4$$udzne
000273922 7001_ $$aHuber-Lang, Markus$$b5
000273922 7001_ $$aMorganti-Kossmann, Cristina$$b6
000273922 7001_ $$0P:(DE-2719)2812851$$aRoselli, Francesco$$b7$$eLast author$$udzne
000273922 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2024.1443940$$gVol. 15, p. 1443940$$p1443940$$tFrontiers in immunology$$v15$$x1664-3224$$y2024
000273922 8564_ $$uhttps://pub.dzne.de/record/273922/files/DZNE-2024-01396.pdf$$yOpenAccess
000273922 8564_ $$uhttps://pub.dzne.de/record/273922/files/DZNE-2024-01396.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000273922 909CO $$ooai:pub.dzne.de:273922$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000273922 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812855$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000273922 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812851$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b7$$kDZNE
000273922 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000273922 9141_ $$y2024
000273922 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-26
000273922 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000273922 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFRONT IMMUNOL : 2022$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-05-11T10:28:02Z
000273922 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-05-11T10:28:02Z
000273922 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000273922 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2021-05-11T10:28:02Z
000273922 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bFRONT IMMUNOL : 2022$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-26
000273922 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-26
000273922 9201_ $$0I:(DE-2719)1910001$$kAG Roselli$$lMetabolic Changes in Neurodegeneration$$x0
000273922 9201_ $$0I:(DE-2719)1910002$$kAG Böckers$$lTranslational Protein Biochemistry$$x1
000273922 980__ $$ajournal
000273922 980__ $$aVDB
000273922 980__ $$aUNRESTRICTED
000273922 980__ $$aI:(DE-2719)1910001
000273922 980__ $$aI:(DE-2719)1910002
000273922 9801_ $$aFullTexts