TIPE2 ameliorates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy through regulating RhoA/ROCK2-NF-κB signaling pathway

Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction induced by systemic inflammation caused by sepsis and is one of the most common types of encephalopathy in intensive care units. Deteriorative neuroinflammation is closely related to the development of brain injury, which often transforms into common pathological manifestations in patients with severe sepsis. Therefore, taking necessary preventive and protective measures for potential brain injury and promptly reducing neuroinflammatory injury is necessary to improve the long-term prognoses of patients. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) can play a significant protective role in septic lung injury, but studies on its expression and role in neurological diseases are rare. In the present study, we found that TIPE2 can expressed in microglia and ameliorate brain injury caused by SAE by suppressing neuroinflammation. The RhoA/ROCK2 pathway is the central coordinator of tissue injury response, and the activation of RhoA participates in the lipopolysaccharide-induced activation of the nuclear factor kappa B (NF-kappa B) signaling pathway. The activation of RhoA and phosphorylation of NF-kappa B was enhanced after TIPE2 deficiency. Importantly, TIPE2 negatively regulates inflammatory responses in vivo and in vitro and plays a protective role in SAE by inhibiting the activation of RhoA/ROCK2-NF-kappa B signaling pathways. The ultimate aim of our proposed project is to provide a theoretical basis for the development of a novel strategy for the early prevention and therapy of SAE.

Automated summary

Sepsis-associated encephalopathy (SAE) is a common type of brain dysfunction caused by systemic inflammation. In this study, TIPE2 was found to be expressed in microglia and can ameliorate brain injury caused by SAE by suppressing neuroinflammation. It plays a protective role in SAE by inhibiting the activation of the RhoA/ROCK2-NF-kappa B signaling pathways.