Points in time at which a difference was observed (marked by + in a grey box) between the hemisphere of tumor cell injection and the contralateral hemisphere, shown separately for each MR parameter analyzed.

<p>Points in time at which a difference was observed (marked by + in a grey box) between the hemisphere of tumor cell injection and the contralateral hemisphere, shown separately for each MR parameter analyzed.</p

Spatial heterogeneity of cerebral blood volume (CBV) and signal recovery (SR).

<p>Maps of SR (purple) were overlaid on maps of CBV (green) obtained on day 21 after injection of 100,000 C6 cells. Areas of increased CBV were mostly found at the tumor rim whereas signal recovery exceeding the baseline was mainly seen in the tumor center excluding regions which were most likely necrotic (dark on T2 weighted images). Coronally and axially oriented T2-weighted images (T2w) are shown as reference.</p

Simulated signal-intensity time curve after administration of the contrast agent.

<p>Left: schematic illustration of signal recovery (SR) and percentage of signal recovery (PSR). SR is defined as the difference between the signal intensity immediately after the first pass of the contrast agent (S_post at t_post, in humans usually 60 s after bolus arrival) and the pre-contrast (S_pre) signal intensity, while PSR is given by the difference of the signal intensity at t_post to the minimum of the signal intensity-curve (S_min) divided by the difference between pre-contrast (S_pre) and minimum (S_min) signal intensity. Right: Influence of TR and TE on the signal-intensity time curve. The stronger the T1-weighting (reduction of TR) and the weaker the T2*- weighting (reduction of TE) the higher S_min and S_post for the identical time curve of the contrast agent concentration (solid line: TR/TE = 1500/50 ms, dashed line: TR/TE = 1200/50 ms, dotted line: TR/TE = 1500/40 ms assuming T1/T2 = 1000/100 ms and r1/r2 = 4/5 l mmol^-1 s^-1).</p

Robustness of signal recovery (SR) and percentage of signal recovery (PSR) maps.

<p>In case of alteration of the bolus peak PSR maps became unusable, while SR still provided exploitable results. On the right the corresponding axially oriented T2-weighted image.</p

Time course of tumor development after intracerebral injection of 10,000 C6-glioma cells.

<p>T2-weighted images (T2w) revealed an increase in tumor mass over time which was accompanied by an increasing area of contrast enhancement (G1-T1w). At day 9 maps of percentage of signal recovery (PSR) and signal recovery (SR) indicated a higher capillary permeability in the tumor center (white ring) extending over time. Higher PSR and SR values were also seen in the region of the choroid plexus (open arrow). Higher cerebral blood volume (CBV) was mainly found at the tumor rim (white arrow and ring).</p

Cerebral blood volume (CBV) and vessel density.

<p>The highest CBV was found at the rim of the tumor which also showed the highest vessel density (bar graph) as revealed by immunohistochemistry for von Willebrand factor (vWF, lower row): (left) overview showing the position of the magnified view of the tumor rim (orange box) and tumor center (green box), upper row, left: the corresponding axially oriented T2-weighted image.</p

Additional file 2: of Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis

Axons undergoing Wallerian degeneration are at least in part myelinated in EAE lesions. No co-localization of NPY-Y1R immunoreactivity with myelin proteins, i.e., PLP (A-C), MOG (D-F), MAG (G-I), and CNPase (J-L) was observed by fluorescence double IHC in WT EAE mice, which further confirms that the antiserum against NPY-Y1R applied does not detect an antigen situated within the myelin sheath or myelin ovoids. Insets in (A-C) represent NPY-Y1R+ degenerating fiber(s) in largely intact myelinated tracts, as determined by anti-PLP IHC. Scale bars=(A-L) 200 μm; (insets A-C) 10 μm. (JPG 673 kb

Maps of signal recovery (SR), percentage of signal recovery (PSR) and cerebral blood volume (CBV) in comparison.

<p>Recovery of signal intensity at baseline level corresponds to a value of 0% on the SR map and 100% on the PSR map (black arrow). For better comparison the maps were scaled in a way that these two values marked the end of the first third of the entire value range of the respective map. Thus, with the used color coding, regions with a signal increase above baseline appeared yellow to red while those in which the signal intensity did not recover to baseline appeared blue on both maps. The signal-intensity time curve of selected regions of interest (ROI) is shown on the right, lower row. PSR and SR revealed a similar spatial distribution of regions with an increased capillary permeability, with highest level in the tumor center (blue ROI). Low PSR and SR were mostly accompanied by high CBV values (red ROI), whereas the signal intensity on the contralateral side went back to baseline (yellow ROI) within the observation time.</p

Distribution of GFP labeled SC after delivery in the cisterna magna and the spinal cord.

<p>GFP-SC (green) are detected both in the cerebellar parenchyma (A, B) and meninges (C) 7 days (A–C) after cisterna magna delivery as well as 21 days after in the proximal spinal cord (D). GFP-SCs grafted in the spinal cord parenchyma (E, F) are concentrated around blood vessels, some migrate away from the graft toward a lesion (L) identified by MOG immunostaining through white matter (E, arrows). (F) Same field illustrating GFP-SCs, inset is a higher magnification.</p

One route of SC migration: the blood vessels.

<p>SC grafted in the spinal cord parenchyma are often localized in white matter around blood vessels (asterisks), evidenced with anti-laminin antibody (blue). While at 7 days SC are present close to the blood vessel wall (A), at 21 days they are embedded in the perivascular space but remote from the vascular wall (B).</p