Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway.

Yuqin Ye,Yanfeng Jia,Ze Li,Chen Chen,Xinhong Su,Yongxiang Yang,Chaoxian Wang,Xiaosheng He

doi:10.1155/2017/5841814

Yuqin Ye, Yanfeng Jia + Show 6 more

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https://doi.org/10.1155/2017/5841814

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Abstract

The protective role of electroacupuncture (EA) treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI) remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4) signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

Highlights

As one of the leading life-threatening diseases worldwide, traumatic brain injury (TBI) often causes high mortality or a range of severe neurological deficits and long-term disability due to an inadequate self-repair capacity of the central nervous system (CNS) [1]
We further investigated the effect of EA treatment on inflammatory cytokine expression in the downstream of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor-κB (NF-κB) and TLR4/toll/IL-1 receptor domaincontaining adapter-induced interferon-β (TRIF)/NF-κB axles at 35 days after TBI
Our results showed that the TBI-induced hippocampal NF-κB elevation was significantly inhibited by EA treatment, which varied in the similar pattern to Myd88, TRAF6, TRIF-related adaptor molecule (TRAM), and TRIF

Summary

Introduction

As one of the leading life-threatening diseases worldwide, traumatic brain injury (TBI) often causes high mortality or a range of severe neurological deficits and long-term disability due to an inadequate self-repair capacity of the central nervous system (CNS) [1]. The remarkable characteristics of hippocampal NSCs include self-renew, production of newborn neurons, and integration into the damaged neural network following CNS injury, which makes intervention of endogenous neurogenesis as an attracting strategy for the rehabilitation of injured brain. In recent years, increasing studies have indicated that EA was conducive to the improvement of neurological function following CNS damage via stimulation of certain acupuncture points, whereas the detailed mechanism was still not fully understood [8,9,10].

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