Overexpression of S100B promotes depressive-like behaviors in stroke-induced rats by modulating the PI3K/AKT/NF-κB pathway

Post-stroke depression (PSD) is a common complication following a stroke, primarily characterized by low mood, cognitive sluggishness, and sleep disturbances. Currently, the precise pathogenic mechanisms underlying PSD remain elusive. Research indicates that S100B protein levels may serve as a specific biochemical marker of organic brain injury, with significantly elevated serum S100B levels noted in patients with ischemic stroke, depression, and schizophrenia. S100B facilitates apoptosis through various cellular signaling pathways and is implicated in inflammatory responses, thereby participating in the pathophysiology of numerous diseases. Nonetheless, the role of elevated S100B expression in PSD remains unclear. This study used a PSD rat model created by combining MCAO and CUMS to evaluate depressive behaviors. The expression of S100B and proteins associated with the PI3K/AKT/NF-κB signaling pathway was analyzed, while changes in inflammatory factors such as IL-1, IL-6, and TNF-α were quantified using ELISA. The findings demonstrated that the combination of MCAO and CUMS effectively induced depressive-like behaviors in the rats. In the PSD rat model, overexpression of S100B may inhibit the PI3K/AKT pathway and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors such as IL-1, IL-6, and TNF-α, which exacerbate brain tissue damage. However, the administration of S100B inhibitors improved depressive-like behaviors in PSD rats and reversed the alterations in the aforementioned signaling pathways and inflammatory factors. These findings advance the understanding of PSD pathogenesis and suggest therapeutic strategies.