Tauroursodeoxycholic acid attenuates neuronal apoptosis via the TGR5/ SIRT3 pathway after subarachnoid hemorrhage in rats

Huihui Wu,Yina Yang,Nini Yu,Xia Wang,Hui Liang

doi:10.1186/s40659-020-00323-1

Huihui Wu, Yina Yang + Show 3 more

Open Access

https://doi.org/10.1186/s40659-020-00323-1

Copy DOI

Abstract

BackgroundNeuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH.MethodsSprague–Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated.ResultsTUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA.ConclusionsOur findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.

Highlights

Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH)
Previous studies have showed that Tauroursodeoxycholic acid (TUDCA) can significantly reduce brain injury and improve neurological function associated with acute hemorrhagic stroke or acute ischemic stroke in rats through inhibiting neuronal apoptosis [5, 6]
TUDCA improved neurobehavioral functions and reduced brain edema at 24 h and 72 h after SAH The neurological scores of modified Garcia were significantly reduced at 24 h in the SAH + vehicle group (P < 0.05 versus Sham) (Fig. 1a)

Summary

Introduction

Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH. There is compelling evidence to suggest that neuronal apoptosis play a pivotal role in the development of early brain injury after. SAH and apoptosis inhibition by pharmacological treatment could protect against brain injury after SAH [3]. Tauroursodeoxycholic acid (TUDCA) is an endogenous hydrophilic bile acid used clinically to treat certain liver diseases [4]. Previous studies have showed that TUDCA can significantly reduce brain injury and improve neurological function associated with acute hemorrhagic stroke or acute ischemic stroke in rats through inhibiting neuronal apoptosis [5, 6]. TGR5 is a plasma membranebound G protein-coupled bile acid receptor, which has varied levels of expression in different tissues including brain [7, 8]

Methods

Results

Discussion

Conclusion