Additional file 1:Â Figure S1-S14. of Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945
Creators: name: Beckmann, Nicolau
name: Giorgetti, Elisa
name: Neuhaus, Anna
name: Zurbruegg, Stefan
name: Accart, Nathalie
name: Smith, Paul
name: Perdoux, Julien
name: Perrot, Ludovic
name: Nash, Mark
name: Desrayaud, Sandrine
name: Wipfli, Peter
name: Frieauff, Wilfried
name: Shimshek, Derya
Publisher: name: figshare
Year: 2018
Subjects: subject: Space Science
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Neuroscience
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Plant Biology
subject: 60506 Virology

description: Figure S1. 5-week cuprizone intoxication leads to demyelination and neuroinflammation in the corpus callosum when compared to healthy control. Figure S2. MRI reliably detects de- and re-myelination events in the cuprizone model in the corpus callosum/external capsule (cc+ec), correlating with myelin and oligodendrocyte histology. Figure S3. BLZ945 dose-response and time-course on microglia depletion and activation in the brain. Figure S4. BLZ945 dose-response on microglia-specific gene expression and microglia depletion in the spinal cord. Figure S5. Longitudinal MRI measurements of a 2-week therapeutic treatment with BLZ945 (169 mg/kg p.o., qd) after 5-week cuprizone intoxication. Figure S6. A 2-week therapeutic treatment with BLZ945 after 5-week cuprizone intoxication period enhanced remyelination but depleted NG2-positive oligodendrocyte precursor cells. Figure S7. A 2-week therapeutic treatment with BLZ945 after a 5-week cuprizone intoxication period changed microglia morphology. Figure S8. A 2-week therapeutic treatment with BLZ945 after a 5-week cuprizone intoxication period enhanced astrogliosis. Figure S9. Therapeutic BLZ945 treatment in experimental autoimmune encephalomyelitis (EAE) mice did not alter disease progression. Microglia in the spinal cord were reduced, whereas in the cortex no reduction, but enhanced microglia proliferation could be observed. Figure S10. Longitudinal MRI measurements of prophylactic treatment with BLZ945 1 week before and during the 5-week cuprizone intoxication. Figure S11. Prophylactic treatment with BLZ945 before and during cuprizone intoxication led to axonal pathology, myelin debris and reduced NeuN-positive cells in cortex. Figure S12. Prophylactic treatment with BLZ945 before and during cuprizone intoxication showed similar levels of astrocytosis as well as increase in LAMP1 in external capsule (ec) and corpus callosum (cc). Figure S13. 5-week cuprizone intoxication in TREM2 knock-out mice led to enhanced pathology especially in the external capsule. Figure S14. Quantitative image analysis of microglia/astrocyte numbers and morphology of stained Iba1 and GFAP brain sections. (PDF 13675Â kb)