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

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

doi:10.1155/2017/5841814

Cited by 22 publications

(23 citation statements)

References 68 publications

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“…Studies have reported that TLR4 in the central nervous system (CNS) involved in memory, learning impairment [10] and cognitive decline [11]. Recently, TLR4 was also identified as a modulator of neurogenesis in the brain during injuries, cerebral ischemia, and cognitive decline [12], and it is recognized to contribute to neuroplasticity [13]. Studies demonstrated that cognitive dysfunction was alleviated possibly by inhibiting hippocampal TLR4 activation in aged rats [14].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4-KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

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Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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“…To the best of our knowledge, TLR4/MyD88/MAPK/NF-κB signal pathway was one of the classical pathways in ischemic stroke‑induced inflammation. Many drugs [ 50 , 51 ] and treatments [ 52 ] could inhibit the TLR4-mediated inflammatory responses and decrease proinflammatory cytokine release through the MyD88-dependent signaling pathway. MyD88-dependent signaling contributes to the inflammatory responses induced by cerebral ischemia/reperfusion [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying the pattern of immune related cells and genes in the peripheral blood of ischemic stroke

Cui

Feng

et al. 2020

J Transl Med

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Background Ischemic stroke (IS) is the second leading cause of death worldwide which is a serious hazard to human health. Evidence suggests that the immune system plays a key role in the pathophysiology of IS. However, the precisely immune related mechanisms were still not been systematically understood. Methods In this study, we aim to identify the immune related modules and genes that might play vital role in the occurrence and development of IS by using the weighted gene co-expression network analysis (WGCNA). Meanwhile, we applied a kind of deconvolution algorithm to reveal the proportions of 22 subsets of immune cells in the blood samples. Results There were total 128 IS patients and 67 healthy control samples in the three Gene Expression Omnibus (GEO) datasets. Under the screening criteria, 1082 DEGs (894 up-regulated and 188 down-regulated) were chosen for further analysis. A total of 11 clinically significant modules were identified, from which immune-related hub modules and hub genes were further explored. Finally, 16 genes were selected as real hub genes for further validation analysis. Furthermore, these CIBERSORT results suggest that detailed analysis of the immune subtype distribution pattern has the potential to enhance clinical prediction and to identify candidates for immunotherapy. More specifically, we identified that neutrophil emerge as a promising target for IS therapies. Conclusions In the present study, we investigated the immune related gene expression modules, in which the SLAMF1, IL7R and NCF4 may be novel therapeutic targets to promote functional and histological recovery after ischemic stroke. Furthermore, these hub genes and neutrophils may become important biological targets in the drug screening and drug designing.

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“…These treatments were able to alleviate the nerve damage and promote neurological recovery after TBI. Electro-acupuncture-induced TLR4 signaling inhibition has been used to promote hippocampal neurogenesis and neurological recovery post-trauma [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo

Liu

Chen

Meng

et al. 2018

J Neuroinflammation

146

111

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BackgroundTraumatic brain injury (TBI) is a critical public health and socioeconomic problem throughout the world. Inflammation-induced secondary injury is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced inflammation.MethodsIn this study, mice with genetically ablated caspase-1 (caspase-1−/−) were subjected to controlled cortical impact injury in vivo, and primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP in vitro. We evaluated the effects of caspase-1 deficiency on neurological deficits, inflammatory factors, histopathology, cell apoptosis, and pyroptosis.ResultsDuring the acute post-injury period (0–48 h) in vivo, motor deficits, anti-inflammatory cytokines (TGF-β and IL-10), pro-inflammatory cytokines (IFN-γ, IL-1β, and IL-18), and blood lactate dehydrogenase (LDH), as well as pyroptosis-related proteins (caspase-1, caspase-1 fragments, caspase-11 and GSDMD), were increased. Caspase-1 was activated in the cortex of TBI mice. Inflammatory activation was more profound in injured wild-type mice than in caspase-1−/− mice. In vitro, mechanical scratch, equiaxial stretch, and LPS/ATP-induced neuron pyroptosis, apoptosis, LDH release, and increased expression of inflammatory factors. The effects of mechanical and inflammatory stress were reduced through inhibition of caspase-1 activity through siRNA knockdown and pharmacologic inhibition.ConclusionCollectively, these data demonstrate that pyroptosis is involved in neuroinflammation and neuronal injury after TBI, and ablation of caspase-1 inhibits TBI-induced pyroptosis. Our findings suggest that caspase-1 may be a potential target for TBI therapy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1083-y) contains supplementary material, which is available to authorized users.

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

Cited by 22 publications

References 68 publications

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Identifying the pattern of immune related cells and genes in the peripheral blood of ischemic stroke

Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo

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