MOESM1 of Human Skeletal Muscle Stem Cell Antiinflammatory Activity Ameliorates Clinical Outcome in Amyotrophic Lateral Sclerosis Models

Human Skeletal Muscle Stem Cell Antiinflammatory Activity Ameliorates Clinical Outcome in Amyotrophic Lateral Sclerosis Model

Additional file 6: of Characterization of the biological processes shaping the genetic structure of the Italian population

PCA of the Italian dataset using the 270 PC1-associated SNPs. Plot of the first two principal components showing that the 270 SNPs recreate the genetic latitudinal gradient observed in Italy. (PDF 73 kb

L'Écho : grand quotidien d'information du Centre Ouest

10 septembre 19381938/09/10 (A67).Appartient à l’ensemble documentaire : PoitouCh

Image_1_Spectral exponent assessment and neurofilament light chain: a comprehensive approach to describe recovery patterns in stroke.TIF

IntroductionUnderstanding the residual recovery potential in stroke patients is crucial for tailoring effective neurorehabilitation programs. We propose using EEG and plasmatic Neurofilament light chain (NfL) levels as a model to depict longitudinal patterns of stroke recovery.MethodsWe enrolled 13 patients (4 female, mean age 74.7 ± 8.8) who underwent stroke in the previous month and were hospitalized for 2-months rehabilitation. Patients underwent blood withdrawal, clinical evaluation and high-definition EEG at T1 (first week of rehabilitation) and at T2 (53 ± 10 days after). We assessed the levels of NfL and we analyzed the EEG signal extracting Spectral Exponent (SE) values. We compared our variables between the two timepoint and between cortical and non-cortical strokes.ResultsWe found a significant difference in the symmetry of SE values between cortical and non-cortical stroke at both T1 (p = 0.005) and T2 (p = 0.01). SE in the affected hemisphere showed significantly steeper values at T1 when compared with T2 (p = 0.001). EEG measures were consistently related to clinical scores, while NfL at T1 was related to the volume of ischemic lesions (r = 0.75; p = 0.003). Additionally, the combined use of NfL and SE indicated varying trends in longitudinal clinical recovery.ConclusionWe present proof of concept of a promising approach for the characterization of different recovery patterns in stroke patients.</p

mRNA expression of cytokines and trophic factors in ischemic cortex at day 1.

<p>Data are expressed as fold of induction compared to sham/PBS group (mean±SEM, n = 6). Two-way ANOVA: SDF-1α F: 97.52, p<0.0001; TGF-β1 F: 31.54, p = 0.0001; VEGF-A F: 24.14, p = 0.0004; IGF-1 F: 28.21, p = 0.0002; BDNF F: 19.34, p = 0.0009. <i>Posthoc</i> Bonferroni test: **p<0.01, ***p<0.001 vs sham/PBS; °°°p<0.001 vs isch/PBS; ### p<0.001 vs sham/NC(4 h).</p

Experimental design.

<p>NC were infused icv either 4 h (A) or 7 d (B) after ischemia. Histology, immunohistochemistry, confocal microscopy, real time PCR, behavioural test and neuronal count experiments were performed at the time points indicated.</p

Open field test and neuronal loss in ischemic brain areas at day 14.

<p> Mice receiving NC(4 h), but not those receiving NC(7 d) show a reversal of ischemia-induced impairment in number of rears and objects (A, n = 10) and a significant reduction in neuronal loss in striatum and cortex (B) compared to those receiving PBS (n = 6). Data are expressed as mean±SEM. One-way ANOVA: (A) rears F: 11.46, p<0.0001; (A) objects F: 5.38, p = 0.0056; (B) striatum F: 31.67, p<0.0001; (B) cortex F: 5.06, p = 0.0256. <i>Posthoc</i> Tukey test: °° p<0.01, °p<0.05 vs isch/PBS, ** p<0.01, * p<0.05 vs controls; §§§ p<0.001, § p<0.05 vs isch/NC(4 h).</p

Open field test and neuronal loss in ischemic brain areas at day 7.

<p>Mice receiving NC(4 h) show a reversal of ischemia-induced impairment in number of rears and objects, (A, n = 10) and a significant reduction in neuronal loss in striatum and cortex (B) compared to those receiving PBS (n = 6). Fibroblast infusion 4 h after ischemia does not significantly affect open field impairment and neuronal loss (n = 7). Data are expressed as mean±SEM. One-way ANOVA: (A) rears F: 6.122, p = 0.0002; (A) objects F: 16.10, p<0.0001; (B) striatum F: 17.67, p = 0.0002; (B) cortex F: 37.01, p<0.0001. <i>Posthoc</i> Tukey test: °° p<0.01, °p<0.05 vs isch/PBS; ** p<0.01 *p<0.05 vs controls; §§§ p<0.001 vs isch/NC(4 h).</p

Confocal analysis of immunoreactivity of NC (green) and microglia/macrophages (red).

<p>CD11b immunoreactivity signal, staining for microglia/macrophages, colocalizes with that of NC(4 h) in striatum at day 1 (A–C) and 7 (D–F). Z- stacks are shown. Bar: 25 µm.</p

Figure 4

<p>(A) Changes in extracellular pH <u>(pH_e)</u> in the PC and in mOT induced by ipsilateral MCA occlusion and reperfusion. Occlusion induced a rapid metabolic acidification of the extracellular microenviroment in PC, interrupted by a transient and mild basification (arrow) associated to the hypoxic spreading depression (HD, asterisk). No changes in extracellular [H⁺] were recorded in the mOT, that is not served by the MCA. (B) Simultaneous changes in extracellular potassium concentration ([K⁺]_o)and extracellular pH in the PC after MCA occlusion and reperfusion. An initial enhancement in [K⁺] was followed by a fast and large increase in [K⁺]_o. associated to the HD. The schematic drawing on the right illustrates the position of the two-barrel recording electrodes. The field responses (FP) recorded with the conventional extracellular barrel are also shown. The period of MCA occlusion is marked by the shaded area.</p