Abstract: Objective To evaluate the effect of modulating gut microbiota for improving brain injury in rats with post-stroke depression. Methods Adult SD rats were randomized into normal control, middle cerebral artery occlusion (MCAO), post-stroke depression (PSD), PSD with fecal transplantation, PSD with antibiotics (rifaximin), PSD with probiotics (lactobacilli), and PSD with fluoxetine treatment groups (n=9). Neurological function scores of the rats were determined, and the changes in sugar water preference and immobility time in forced swimming test were observed; plasma levels of trimethylamine N-oxide (TMAO) and hydrogen sulfide (H2S) were detected with ELISA, Occludin, and the expressions of occludin, caudin-5 and IgG proteins I the brain tissues were determined using Western blotting. Results Compared with those in the control group, the rats in MCAO and PSD groups had significantly increased neurological function scores, TMAO level, the ratio of TMAO/H2S, and immobility time in forced swimming test with a lowered level of H2S (P<0.05). These changes were more obvious in PSD rats, which also exhibited a reduced sugar water preference with increased IgG protein and decreased occluding and caudin-5 expressions in the brain tissue (P<0.05). TMAO/H2S ratio in PSD rats was positively correlated with neurological function score (R2=0.3235, P=0.0269) and immobility time in swimming (R2=0.6290, P=0.0004) and negatively with sugar water preference (R2=-0.4534, P=0.0059). Treatment with fecal transplantation, antibiotics, probiotics and fluoxetine all significantly reduced neurological function scores, immobility time in forced swimming, TMAO/H2S ratio, and IgG protein expression and increased sugar water preference and brain occludin and caudin-5 expressions of the PSD rats (P<0.05). Conclusion In PSD rats, TMAO/H2S ratio is correlated with neurological function score, immobility time in forced swimming and sugar water preference, and modulating intestinal flora can improve neurological function and depressive symptoms and improve the integrity of the blood-brain barrier.

Key words: post-stroke depression; TMAO/H2S; intestinal flora; blood-brain barrier