The Attenuation of Traumatic Brain Injury via Inhibition of Oxidative Stress and Apoptosis by Tanshinone IIA.

Yongpan Huang,Pan Zhang,Xiang Zhang,Chunyan Luo,Xinliang Li,Yan Zhou,Jiayu Tang,Xian Long

doi:10.1155/2020/4170156

Abstract

Traumatic brain injury (TBI) is a major source of mortality and long-term disability worldwide. The mechanisms associated with TBI development are poorly understood, and little progress has been made in the treatment of TBI. Tanshinone IIA is an effective agent to treat a variety of disorders; however, the mechanisms of Tanshinone IIA on TBI remain unclear. The aim of the present study was to investigate the therapeutic potential of Tanshinone IIA on TBI and its underlying molecular mechanisms. Changes in microvascular permeability were examined to determine the extent of TBI with Evans blue dye. Brain edema was assessed by measuring the wet weight to dry weight ratio. The expression levels of CD11, interleukin- (IL-) 1β, and tumor necrosis factor- (TNF-) α mRNA were determined by reverse transcription-quantitative PCR. Aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), and p47phox protein expression levels were detected by western blotting. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-PX) activities, and malondialdehyde (MDA) content were determined using commercial kits. Cell apoptosis was detected by western blotting and TUNEL staining. Tanshinone IIA (10 mg/kg/day, intraperitoneal administration) significantly reduced brain water content and vascular permeability at 12, 24, 48, and 72 h after TBI. Tanshinone IIA downregulated the mRNA expression levels of various factors induced by TBI, including CD11, IL-1β, and TNF-α. Notably, CD11 mRNA downregulation suggested that Tanshinone IIA inhibited microglia activation. Further results showed that Tanshinone IIA treatment significantly downregulated AQP4 and GFAP expression. TBI-induced oxidative stress and apoptosis were markedly reversed by Tanshinone IIA, with an increase in SOD and GSH-PX activities and a decrease in the MDA content. Moreover, Tanshinone IIA decreased TBI-induced NADPH oxidase activation via the inhibition of p47phox. Tanshinone IIA attenuated TBI, and its mechanism of action may involve the inhibition of oxidative stress and apoptosis.

Highlights

Traumatic brain injury (TBI) is the most common cause of mortality and disability worldwide, and the damages induced by TBI can worsen the quality of life of the patients [1]
The brain damage following TBI is characterized by two phases, the initial, or primary, phase is characterized by direct cerebral tissue damage which results in glutamate release, calcium homeostasis disruption, N-methyl-D-aspartate receptor activation, permeability increase, and consecutive edema formation, which is an important self-protective mechanism to minimize the extent of the damage immediately after TBI
The blood-brain barrier (BBB) is a specialized structure in the central nervous system that can block the entry of macromolecular substances from the peripheral blood into the brain parenchyma, maintaining cerebral homeostasis

Summary

Introduction

Traumatic brain injury (TBI) is the most common cause of mortality and disability worldwide, and the damages induced by TBI can worsen the quality of life of the patients [1]. The first response phase involves diverse cellular and molecular mechanisms that are important to maintain the homeostasis of the damaged tissue [2]. These events may cause cellular structural damage, neuronal cell death, oxidative stress, brain edema, blood-brain barrier (BBB) breakdown, and inflammation [3]. Among these adverse factors, edema formation is considered to be a key to the consequences of TBI, which may deteriorate the prognosis.

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