Figure 9. Mild maternal hypothermia mitigated neurodevelopmental damages.

(A) A sham operation (Control) or maternal uterine artery occlusion (Occluded and Hypothermia) was performed at E16.5. During the occlusion period, the dam was maintained on a warmer set at a temperature of 37.5°C (Occluded) or 25.5°C (Hypothermia). Brains were analyzed 12 hours after occlusion. Sections were immunostained with anti-PH3 antibody. Scale bar: 200 μm. (B) The numbers of PH3-positive cells in the VZ and SVZ are shown (n = 7, respectively). **P < 0.01, ***P < 0.001, Tukey-Kramer test. (C) GFP plasmid was transfected at E16.5 and immediately followed by performance of a sham operation (Control) or maternal uterine artery occlusion (Occluded and Hypothermia). During the occlusion period, the dam was maintained on a warmer set at a temperature of 37.5°C (Occluded) or 25.5°C (Hypothermia) as in A. Brains were analyzed at P3.5. Sections were counterstained with DAPI (blue). Scale bar: 200 μm. (D) Cell distribution was evaluated by bin analysis. (E) Relative migration distances (%) from the ventricle are shown (n = 7, each). ***P < 0.001, Tukey-Kramer test. (F) Performance in the novel object recognition test (NORT). Top: exploratory index. Bottom: total exploration time. Values are mean ± SEM (n = 11 each). ***P < 0.001, repeated-measures ANOVA followed by Bonferroni post-hoc test. (G) The graph indicates the spontaneous alteration behavior in the Y-maze test (Control: n = 13, Occluded: n = 14, Hypothermia: n = 15). ***P < 0.001, Tukey-Kramer test. (B, E, F, and G) Each point represents an individual mouse. Box-and-whisker plots were used to graphically represent the median (line within box), upper and lower quartiles (bounds of box), and maximum and minimum values (top and bottom bars).