Rosuvastatin Alleviates Intestinal Injury by Down-Regulating the CD40 Pathway in the Intestines of Rats Following Traumatic Brain Injury.

Yangchun Hu,Weiwei Chen,Xiaojian Wang,Chao Li,Hongwei Cheng,Lei Ye

doi:10.3389/fneur.2020.00816

Abstract

Statins have been reported to suppress CD40 expression and nuclear factor (NF)-κB activation, which are both up-regulated in the intestines following traumatic brain injury (TBI)-induced intestinal injury. In this study, we aimed to investigate the effects of the statin rosuvastatin on post-TBI jejunal injury in rats, focusing on potential mechanisms involving the CD40/NF-κB signaling pathway. The jejunal CD40 expression was determined by western blotting. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assays (EMSAs). The tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels were assessed by enzyme-linked immunosorbent assays (ELISAs). The severity of the jejunal mucosal injury was assessed by hematoxylin and eosin (HE) staining and histopathological evaluation. We found that the post-TBI upregulation of both CD40 expression and NF-κB activity in the jejunal tissues were significantly inhibited by rosuvastatin, while the post-TBI expression of TNF-α and IL-1β was significantly suppressed by rosuvastatin. In addition, rosuvastatin significantly ameliorated TBI-induced effects on the villus height, crypt depth, and villous surface area. Rosuvastatin suppressed TBI-induced intestinal injury in rats, which may be associated with the blockade of the CD40/NF-κB pathway.

Highlights

Traumatic brain injury (TBI) is a serious medical problem worldwide, with extremely high disability and mortality rates [1]
We found increases in the CD40 protein level, nuclear factor (NF)-κB DNA-binding activity, and concentrations of IL-1β and tumor necrosis factor (TNF)-α in the jejunal tissues of rats at 24 h after traumatic brain injury (TBI)
Histopathological evaluation confirmed that the TBI-induced damage to the jejunal structures was ameliorated by rosuvastatin

Summary

Introduction

Traumatic brain injury (TBI) is a serious medical problem worldwide, with extremely high disability and mortality rates [1]. Intensive investigations of TBI have been carried out, researchers have focused mainly on the pathophysiologic processes of the brain injury itself. It is important to realize that extracranial complications following the initial brain injury might, to some extent, impede treatment efficacy, and recovery. Understanding the etiology and underlying mechanisms of post-TBI extracranial complications is important [2]. We demonstrated that TBI can induce marked damage to intestinal mucosal structures and barrier functions [4]. We found that TBI up-regulated the intestinal expression of CD40, nuclear factor (NF)-κB, and pro-inflammatory cytokines, which may play pivotal roles in the pathogenesis of acute intestinal mucosal injury

Objectives

Methods

Results

Conclusion