Blood brain barrier BCAN Brevican BDNF Brain-derived neurotrophic factor C3 Complement C3 Caspr Contactin-associated protein Cdk Cyclin-dependent protein kinase CHI3L1 Chitinase 3 like 1 CNP 2',3'-cyclic nucleotide 3'-phosphodiesterase CNS Central nervous system CNTN1 Contactin 1 CO-IP Co-Immunoprecipitation CSF2 Colony stimulating factor 2 CSPG Chondroitin sulfate proteoglycans CXCL10 C-X-C motif chemokine ligand 10 CXCL2 C-X-C motif chemokine ligand 2 DRG Dorsal root ganglion EAE Experimental

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... autoimmune encephalomyelitis ECM Extracellular matrix FGF Fibroblast growth factor LIST OF ABBREVIATIONS GBP2 Guanylate binding protein 2 GFAP Glial fibrillary acidic protein GS Glutamine synthetase SUMMARY ously, some of which aid myelin homeostasis and some of which hinder it; several of these are discussed in this work. Overall, reactive astrocytes play a dual role, and concerning myelination the dominant harmful role could be determined by the interplay of secreted molecules with the surrounding extracellular milieu or the state of OPCs/OLs. In summary, a valuable workflow to study the steps of myelination in a reliable and automated manner in vitro was established. Moreover, this work provides important insights into the conserved spectrum of astrocyte-derived secretion cues as well as the alterations in protein and lipid efflux caused by astrocyte reactivity. Furthermore, brevican was introduced as a new relevant factor that regulates CNS myelination. Future work on the complex crosstalk between the ECM, astrocytes and myelination in the brain will yield a better understanding of the mechanistic cascade connecting brevican to myelin regulation in health and disease. Finally, these results may open new avenues for future relevant astrocyte-specific therapies that directly target remyelination.