Intranasal delivery of the CM derived from hPSC-EMSCs promotes brain functional recovery in HIE rats. A) Representative immunofluorescent staining images of DCX, p-ERK and p-CREB in HIE rats in the dentate gyrus (DG). Focused area in the DG is shown with a magnified view (inset) demonstrating DCX/p-ERK or DCX/p-CREB double positive cells (arrowhead). The average intensity was measured in three consecutive coronal sections (bregma -2.0 mm), scale bar: 100 µm. Quantification data represent mean ± SEM, (sham: n = 6, PBS: n = 6, EMSC-CM: n = 6). *, *** and **** represent p < 0.05, 0.001 and 0.0001 respectively by Tukey's post-hoc test when statistical significance by One-way ANOVA (p < 0.05) was obtained; B-D) Assessment of learning and memory function by Morris water maze. sham: n = 8, PBS: n = 6, EMSC-CM: n = 8; B) No difference in escape latency was observed for all rat groups during visible platform conditioning trial; C) EMSC-CM- transplanted rats performed significantly better in learning than PBS - transplanted rats, which was comparable to the normal rats during invisible platform learning trials. *, ** represent p < 0.05 and 0.01 respectively compared to PBS group by Tukey's post-hoc test when statistical significance by Two-way ANOVA (p <0.05) was obtained; D) EMSC-CM- transplanted rats performed significantly better in memory retention than PBS - transplanted rats. *, ** represent p< 0.05 and 0.01by Tukey's post-hoc test when statistical significance by One-way ANOVA (p < 0.05) was obtained.