Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-κB Expression.

Qian Li,Shenquan Cai,Qiuting Zeng,Changsong Zhu,Gao Yu,Xuejun Sun,Pan Yu,Bing Luo,Xingdong Chen,Kangli Hui,Manlin Duan

doi:10.1007/s11064-016-1978-x

Abstract

Recently, it has been suggested that molecular hydrogen (H2) can selectively reduce the levels of hydroxyl radicals (.OH), and ameliorate oxidative and inflammatory injuries to organs in global cerebral ischemia reperfusion models. Global cerebral ischemia/reperfusion (I/R) can induce a sudden activation of inflammatory cytokines and later influence the systemic immunoreactivity which may contribute to a worse outcome. Regulatory T cells (Tregs) are involved in several pathological aspects of cerebral I/R. In addition, miRNA took part in the processes of cellular response to hypoxia. Since the expression of a specific set of miRNA called “hypoxamirs” is upregulated by hypoxia. Therefore, the aim of this study was to analyze the effect of HRS on I/R inducing cerebral damage, Tregs, and specific miRNA. Our results showed that rats undergone global cerebral I/R and treated with HRS have milder injury than I/R animals without HRS treatment. miR-210 expression in the hippocampus of the I/R group at 6, 24 and 96 h after reperfusion was significantly increased at each time point, while its expression in the group treated with HRS was significantly decreased. In addition, Tregs number in group I/R was decreased at each time points, while its number in the group treated with HRS was increased at 24 and 96 h after reperfusion. We focus on the relationship among Tregs, TGF-β1, TNF-α and NF-κB at 24 h, and we found that there is a high correlation among them. Therefore, our results indicated that the brain resuscitation mechanism in the HRS-treated rats may be related with the effect of upregulating the number of Treg cells.

Highlights

Global cerebral ischemia can cause severe central nervous system damage
To investigate the effect of hydrogen rich saline (HRS) on the global cerebral I/R in rats, behavioral test at T1, T2 and T3, qualitative and quantitative analysis of pyramidal cell were performed at T0, T1, T2 and T3
We demonstrated that intraperitoneal injection of HRS at 6 h after cerebral I/R was more efficient than an intraperitoneal injection during reperfusion

Summary

Introduction

Global cerebral ischemia can cause severe central nervous system damage. Some studies suggest that activated immune cells can mediate the central nervous system injury and systemic immune inflammation, due to an early activation caused by acute cerebral ischemia and reperfusion [1]. These reactions are often accompanied by reactive oxygen species production, leading to NF-κB activation, which is involved in the activation of inflammatory gene promoters, and induction of inflammatory cytokines such as TNF-α [2]. Many studies have recently identified T lymphocytes as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is still unclear [3]

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