The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway

Fig. 1. Effect of linagliptin treatment on motor function and infarct volume. a Forepaw grip strength at Day 3 and b 3 weeks after MCAO. c Infarct volume 3 weeks after MCAO. d Photomicrographs of NeuN immunoreactivity. Dashed line outlines the area of visible ischemic damage after MCAO. Unpaired t test with Welch’s correction, mean ± SD. * and ** denote p < 0.05 and p < 0.01 respectively

Fig. 2. Effect of linagliptin treatment on active GLP-1, active GIP and active SDF-1a in serum and brain. Serum levels of active GLP-1 (a), active GIP (b) and active SDF-1α (c) after prolonged linagliptin treatment. Levels of active GLP-1 (d), active GIP (e) and active SDF-1α (f) in the brain after prolonged linagliptin treatment. Unpaired t test with Welch’s correction, mean ± SD. **, ***and **** denote p < 0.01, p < 0.001 and 0.0001 respectively

Fig. 3. Effect of AMD3100 and linagliptin on motor function and tissue damage after MCAO. a Forepaw grip strength at Day 3 after MCAO. b Ischemic volume at Day 3 after MCAO. The number of surviving neurons in the striatum (c) and cortex (d) at Day 3 after MCAO. e Representative photomicrographs of brain sections (NeuN immunostained) used in the quantitative analyses. Solid black line denotes the area of the stroke infarct volume measurement. Solid white line denotes the area of decreased neuronal density after MCAO. Dashed black line denotes the area of neuronal quantification by stereology methods. One-Way ANOVA followed Holm–Sidak’s multiple comparisons test, mean ± SD. * and ** denote p < 0.05 and p < 0.01 respectively and indicate the statistically significant difference over the vehicle group

Fig. 4. Detection of neurogranin peptides. The figure shows signal intensities, means and SD of 6 neurogranin (NEUG)-derived peptides (NEUG 53–78, NEUG 54–78, NEUG 55–78, NEUG 54–75, NEUG 59–78 and NEUG 55–69) in 16 brain samples (LS linagliptin-stroke, VS vehicle stroke, LC linagliptin control, VC vehicle control). The star marks significant differences (ROC-AUC = 1, p < 0.005) between LS and the remainder of samples. The corresponding amino acid sequence is depicted at the top of each graph

Fig. 5. Detection of myelin-basic protein (MBP). The figure shows signal intensities of peptides with means and standard deviations in each group (LS linagliptin-stroke, VS vehicle stroke, LC linagliptin control, VC vehicle control) derived an isoform of myelin basic protein (MBP). The p-value was calculated between LS and the remainder of samples. In all cases the ROC-AUC was 1 for LS