The GPR120 Agonist TUG-891 Alleviates Neuronal Pyroptosis by Inhibiting Endoplasmic Reticulum Stress after Experimental Intraventricular Hemorrhage in Mice

Abstract

Abstract Intraventricular hemorrhage (IVH) is a disease with high disability and mortality rate and lacks specific therapy, and which basic causes lies in the unclear mechanism. Recently, the pyroptosis in central nervous system diseases has received more attention, which is closely related to traumatic brain injury and hemorrhagic stroke. Furthermore, excessive endoplasmic reticulum stress can cause dysfunction of endoplasmic reticulum and even cell pyroptosis by regulating NLRP3 pathway. However, the relationship between pyroptosis and endoplasmic reticulum stress after IVH is unclear. In this study, we investigated the role of endoplasmic reticulum stress and its relationship with pyroptosis in a mouse model of IVH. Our results show that intracerebroventricular injection of autologous blood induced pyroptosis and endoplasmic reticulum stress. The mechanism is that after IVH, the endoplasmic reticulum stress–NLRP3 inflammatory body–pyroptosis pathway is activated, which results in brain tissue damage. This effect can be reversed by the combination of TUG-891 and GPR120. In summary, we revealed that TUG-891 inhibits endoplasmic reticulum stress and reduces neuronal pyroptosis by activating GPR120, which might be a therapeutic target for the treatment of IVH.