Fig. 4.

Upregulation of HMGB1 in the hippocampus–prefrontal cortex circuit caused LTP inhibition and cognitive dysfunction. A–B Immunofluorescence revealed that HMGB1 was significantly upregulated in the hippocampal DG, CA1, and CA3 and the prefrontal cortex at 4 weeks and 8 weeks post-TBI. Data represent the means ± SD (n = 3 mice per group). 2-way ANOVA, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to the Sham group. Scale bar: 50 µm. C Western blot analysis indicating that the level of HMGB1 was significantly upregulated in the hippocampus–prefrontal cortex circuit 4 weeks and 8 weeks post-TBI. Data represent the means ± SD (n = 3 per group). 2-way ANOVA,***p < 0.001 vs. Sham; #p < 0.05, ##p < 0.01 vs. TBI-4w. Each experiment was repeated three times. (D)Glycyrrhizin treatment significantly improved working memory assessed by T-maze at 4 weeks and 8 weeks post-TBI, 2-way ANOVA. E–F Representative hot zone results and discrimination index of two groups in the NOR test, Unpaired t-test. G Representative results of the nest-building assay. Complete rate (%) (H) and score (I) indicating that glycyrrhizin treatment attenuated social behavior. ****p < 0.0001 at 4 weeks and 8 weeks post-TBI. Data represent the means ± SD (n = 10 mice per group). Unpaired t-test, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to the WT group. J–K Glycyrrhizin treatment significantly improved LTP amplitude in the prefrontal cortex at 4 weeks post-TBI, Unpaired t-test. Data represent the means ± SD (n = 9 slopes per group compared to the WT group