S100A8 contributes to postoperative cognitive dysfunction in mice undergoing tibial fracture surgery by activating the TLR4/MyD88 pathway

Lu, Shunmei; Yu, Chanjuan; Liu, Ya-hua; Dong, Huijuan; Zhang, Xiang; Zhang, Susu; Hu, Liu‐Qing; Zhang, Feng; Qian, Yanning; Gui, Bo

doi:10.1016/j.bbi.2014.10.011

Cited by 89 publications

(69 citation statements)

References 50 publications

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“…* P < 0.05 compared to the control + vehicle group, #P < 0.05 compared to the surgery + vehicle group. development of POCD (Cibelli et al, 2010;Lu et al, 2015;Zhang et al, 2014). Among the pro-inflammatory cytokines, IL-1b is thought to serve as a prominent role in the development of POCD.…”

Section: Discussionmentioning

confidence: 98%

“…POCD occurs in patients from 41-75% at 7 days to 18-45% at 3 months postoperatively across different studies, which is associated with a prolonged hospitalization, a reduced quality of life, and an increased morbidity and mortality (Deo et al, 2011). Although various pathological events are reported to be associated with POCD, accumulating evidence has suggested that microglial activation and subsequent neuroinflammation play major roles in the development of POCD (Cibelli et al, 2010;Lu et al, 2015;Zhang et al, 2014). However, the mechanisms underlying microglial activation after surgery remain largely to be determined.…”

Section: Introductionmentioning

confidence: 98%

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NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice

Zhang

et al. 2016

Brain, Behavior, and Immunity

100

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice

Zhang

et al. 2016

Brain, Behavior, and Immunity

100

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“…Our previous in vitro study suggested that high glucose augmented LPS-induced microglial activation and inflammatory cytokine levels, which offered new insight into the pathophysiological relationship between diabetes mellitus and POCD [35]. Our in vivo study showed that S100A8 resulted in microglial activation following the occurrence and development of surgery-induced neuroinflammation and cognitive dysfunction [36]. Activated microglia can release BDNF, which causes prolonged microglial activation [37].…”

Section: Discussionmentioning

confidence: 99%

Induction of Microglial Activation by Mediators Released from Mast Cells

Zhang¹,

Wang²,

Dong³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Microglia are the resident immune cells in the brain and play a pivotal role in immune surveillance in the central nervous system (CNS). Brain mast cells are activated in CNS disorders and induce the release of several mediators. Thus, brain mast cells, rather than microglia, are the “first responders” due to injury. However, the functional aspects of mast cell-microglia interactions remain uninvestigated. Methods: Conditioned medium from activated HMC-1 cells induces microglial activation similar to co-culture of microglia with HMC-1 cells. Primary cultured microglia were examined by flow cytometry analysis and confocal microscopy. TNF- alpha and IL-6 were measured with commercial ELISA kits. Cell signalling was analysed by Western blotting. Results: In the present study, we found that the conditioned medium from activated HMC-1 cells stimulated microglial activation and the subsequent production of the pro-inflammatory factors TNF-α and IL-6. Co-culture of microglia and HMC-1 cells with corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased TNF-α and IL-6 production. Antagonists of histamine receptor 1 (H₁R), H₄R, proteinase-activated receptor 2 (PAR2) or Toll-like receptor 4 (TLR4) reduced HMC-1-induced pro-inflammatory factor production and MAPK and PI3K/AKT pathway activation. Conclusions: These results imply that activated mast cells trigger microglial activation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS inflammation-related diseases.

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“…Similar changes in proinflammatory cytokines and activation of nuclear factor κB signaling in macrophages have been associated with changes in blood-brain barrier permeability, hippocampal neuroinflammation, and subsequent cognitive impairment in mice after tibial fracture (22)(23)(24). However,…”

mentioning

confidence: 96%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and postoperative cognitive dysfunction. Using a model of tibial fracture with intramedullary pinning in male mice, associated with cognitive deficits, we characterized the effects on the primary somatosensory system. Here we show that tibial fracture with pinning triggers cold allodynia and up-regulates nerve injury and inflammatory markers in dorsal root ganglia (DRGs) and spinal cord up to 2 wk after intervention. At 72 h after surgery, there is an increase in activating transcription factor 3 (ATF3), the neuropeptides galanin and neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), as well as neuroinflammatory markers including ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the fractalkine receptor CX3CR1 in DRGs. Using an established model of complete transection of the sciatic nerve for comparison, we observed similar but more pronounced changes in these markers. However, protein levels of BDNF remained elevated for a longer period after fracture. In the hippocampus, BDNF protein levels were increased, yet there were no changes in Bdnf mRNA in the parent granule cell bodies. Further, c-Fos was down-regulated in the hippocampus, together with a reduction in neurogenesis in the subgranular zone. Taken together, our results suggest that attenuated BDNF release and signaling in the dentate gyrus may account for cognitive and mental deficits sometimes observed after surgery.postoperative pain | nerve injury | memory | delirium | neurogenesis

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S100A8 contributes to postoperative cognitive dysfunction in mice undergoing tibial fracture surgery by activating the TLR4/MyD88 pathway

Cited by 89 publications

References 50 publications

NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice

NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice

Induction of Microglial Activation by Mediators Released from Mast Cells

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

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