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Sanchez-Gonzalez, R. ; Koupourtidou, C. ; Lepko, T. ; Zambusi, A. ; Novoselc, K.T. ; Durovic, T. ; Aschenbroich, S. ; Schwarz, V. ; Breunig, C. ; Straka, H.* ; Huttner, H.B.* ; Irmler, M. ; Beckers, J. ; Wurst, W. ; Zwergal, A.* ; Schauer, T.* ; Straub, T.* ; Czopka, T.* ; Trümbach, D. ; Götz, M. ; Stricker, S.H. ; Ninkovic, J.

Innate immune pathways promote oligodendrocyte progenitor cell recruitment to the injury site in adult Zebrafish brain.

Cells 11:520 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brain Injury ; Brain Regeneration ; Innate Immunity Pathways ; Neurogenesis ; Oligodendrocyte Progenitors ; Reactive Gliosis ; Zebrafish; Toll-like Receptors; Neural Stem-cells; Astrocyte Scar Formation; Glial Scar; Regenerative Response; Neuronal Regeneration; Extracellular-matrix; Reactive Astrocytes; Neurite Outgrowth; Ng2 Cells
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 11, Issue: 3, Pages: , Article Number: 520 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Institute(s) Institute of Stem Cell Research (ISF)
Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Grants Deutsche Forschungsgemeinschaft
European Research Council
Helmholtz Portfolio Themen
German Science Foundation Collaborative Research Centre