Dubois-Dalcq M , Williams A , Stadelmann C , Stankoff B , Zalc B , Lubetzki C .

Z99 NS999999 Intramural NIH HHS

	Fig. 1. Time-lapse recording and OPC ablation experiment in transgenic olig2 EGFP zebrafish larva (at 60 h post fertilization) which expresses EGFP both in axons and OPCs. Image of spinal cord (dorsal side up) before and after laser ablation. Membrane bound GFP + oligodendrocyte-lineage cells which had migrated dorsally were targeted by their fluorescence and ablated using approximately five pulses of 440 nm light generated by a Photonics Micropoint Laser System. At time zero after ablation, the oligodendrocyte (arrow) extends new processes into the area vacated by the ablated cell (arrowhead) and later starts to enwrap axons between 3 and 8 h. The larvae were anaesthesized during both ablation and time lapse and then placed on their side on glass-bottomed 35 mm Petri dishes. The time lapse images were captured using 40 × oil-immersion objectives mounted on a motorized Zeiss Axiovert 200 microscope equipped with a Perkin Elmer ERS spinning disk confocal system with a heated stage and chamber to maintain embryos at 28.5oC (Kirby et al., 2006). Figure and Methodology: Courtesy of Norio Takada and Bruce Appel, Vanderbilt University, Tennessee, USA. Scale bar: 24 µm.
	Fig. 2. Early remyelination of a demyelinated lesion with abundant inflammation in a brain biopsy from an MS patient. Pictures were taken from adjacent, sequential sections; the first section (A) was stained with luxol fast blue for myelin and PAS (nuclei are stained blue by hematoxylin) while all other sections were stained by peroxidase immunolabelling for different antigens (B–F). (A) Extensive demyelination with scarce, thin and irregular remyelinated fibres in light blue (arrows). (B) Proteolipid protein antibody stains abundant thin, apparently newly formed myelin sheaths. (C) Oligodendrocytes in the lesion are strongly immunolabelled (in brown) for TPPP/p25, the brain-specific tubulin polymerization promoting protein (Kovacs et al., 2004). Source: Antibody kindly provided by Poul H. Jensen, Aarhus, Denmark. (D–F) Abundant immune cells are detected in the same remyelinating lesion and identified as foamy macrophages (KiM1P in D) as well as T cells stained for CD3 (E) and CD8 (F). Scale bar: 50 µm.
	Fig. 3. The Congo Red derivative BMB is a myelin marker on brain sections (A, B) and is suitable for PET imaging (C). (A) When injected into mice intraperitoneally (40 mg/g), BMB crosses the blood brain barrier and stains the cerebellar white matter (green fluorescence, arrows). (B) When 1 mM of BMB was incubated in vitro on MS brains sections a clear fluorescent staining of the normal appearing white matter (NAWM) was obtained. The demyelinated area (‘Dem’ delineated by dotted line in the upper left corner) was visualized as a lack of staining. In the shadow plaque area (‘Rem’ surrounded by arrowheads), BMB staining is of intermediate intensity between that observed in demyelinated plaques (‘Dem’) and normal appearing white matter (NAWM). (C) CNS PET imaging using [11C]-BMB (about 100 MBq) injected intravenously in an anaesthetized baboon. This 110 min PET examination was performed using an ECAT HR+ camera. The axial slice from PET imaging was co-registered with a corresponding slice of the brain MRI scan. Source: (A) and (B) are Figs 4A and 5F reproduced with ‘Copyright (2006) National Academy of Sciences, USA’ (Stankoff et al., 2006). Scale bar in (A) 300 µm, in (B) 150 µm and in (C) 12 mm.

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