Minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains unclear. In this study, we further investigated the effect and mechanism of S100B, predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. We discovered that S100B expressions and autocrine were significantly increased in MHE rats and astrocytes isolated from MHE rats. Furthermore, we found that S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress caused by MHE astrocytes. Compared to WT astrocytes, impairment of MHE astrocytes supported neuronal growth in co-culture. To sum up, comprehensive-understanding of the impact of S100B-overexpressed MHE astrocyte on MHE pathology may provide insights into the etiology of MHE.

Background: Our previous study revealed that minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains unclear. Methods: In this study, we further investigated the effect and mechanism of S100B, predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. Results: We discovered that S100B expressions and autocrine were significantly increased in MHE rats and astrocytes isolated from MHE rats. Furthermore, we found that S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress caused by MHE astrocytes. Compared to WT astrocytes, impairment of MHE astrocytes supported neuronal growth in co-culture.Conclusions: To sum up, comprehensive-understanding of the impact of S100B-overexpressed MHE astrocyte on MHE pathology may provide insights into the etiology of MHE.