Post-stroke Treatment with GDNF Enhances Neurogenesis in the SVZ, but MANF Promotes Migration of DCX+ Cells toward the Infarction Area
(A) Timeline of treatment. (B) Representative photomicrographs of infarction areas in different groups. (C) Infarction area was similar between groups. Nissl− area expressed as % of the whole area of the hemisphere. (D) Representative photomicrographs of BrdU immunoreactivity in the SVZ. (E) The number of BrdU-stained cells was increased in ipsilateral SVZ of stroke rats receiving three intraventricular injections of GDNF compared to vehicle or MANF treated (dose of 10 μg, n = 5 to 6, one-way ANOVA p < 0.01, *p < 0.05, ***p < 0.001 LSD. (F) Representative photomicrographs of DCX immunoreactivity in the SVZ. (G) GDNF injections increased DCX+ immunoreactivity in the right SVZ compared to the MANF- or vehicle-treated groups by almost 3-fold (one-way ANOVA p < 0.001, ***p < 0.001 TK). (H) Representative photomicrographs of DCX immunoreactivity in the striatum. (I) GDNF or MANF injections increased the recruitment of neuroblasts (DCX+ cells) into the striatum after stroke compared to vehicle by 4- and 2-fold, respectively (one-way ANOVA p < 0.05, *p < 0.05 TK). (J and L) Representative photomicrographs of DCX immunoreactivity in the corpus callosum (J) and infarction zone (L). (K and M) MANF promoted the migration of DCX+ cells toward the right corpus callosum by 3-fold (K; one-way ANOVA p < 0.001, **p < 0.01 TK) and the infarct area of the neocortex by 3-fold (M; one-way ANOVA p < 0.01, **p < 0.01 TK). No effect was observed with GDNF. Scale bars, 2,000 μm (B) and 50 μm (D–L). LSD, Fisher’s LSD post hoc test; TK, Tukey’s post hoc test. Data are presented as mean ± SEM.