Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

Ren, Hao; Chen, Xuri; Tian, Mengya; Zhou, Jing; Ouyang, Hongwei; Zhang, Zhiyong

doi:10.1002/advs.201800529

Cited by 54 publications

(48 citation statements)

References 253 publications

(348 reference statements)

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“…In addition, inflammatory cells also release excess reactive oxygen species and reactive nitrogen species [66,67], which causes DNA oxidative damage, proteins oxidation and lipid peroxidation [68]. Necrosis and apoptosis of neurons and glial cells are further induced by this process [69,70].…”

Section: Discussionmentioning

confidence: 99%

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

Nakamura

Tang

Zhao

et al. 2020

Preprint

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Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

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Section: Discussionmentioning

confidence: 99%

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

Nakamura

Tang

Zhao

et al. 2020

Preprint

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“…(d) AS‐IV ameliorates secondary damage in the injured spinal cord and promotes locomotor function recovery after SCI in rats. Neuronal apoptosis and neuroinflammation are extremely important in the pathological process of secondary injury after SCI . Numerous studies have targeted these two pathological processes for SCI therapy; however, barely any therapies could target both these two pathological processes.…”

Section: Discussionmentioning

confidence: 99%

“…We found that (a) AS-IV promotes autophagy and inhibits neuronal apoptosis after SCI. 8,[23][24][25] Numerous studies have targeted these two pathological processes for SCI therapy; however, barely any therapies could target both these two pathological processes. In our study, we found that AS-IV possesses 'one stone two birds' potential, which not only inhibits neuronal apoptosis but also suppresses neuroinflammation through inhibiting the mTORC1 signalling pathway (Figure 9).…”

Section: Discussionmentioning

confidence: 99%

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Lin

Pan

Huang

et al. 2019

J Cellular Molecular Medi

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Inflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS‐IV), in vitro and in vivo. Our results showed that AS‐IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS‐IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS‐IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS‐IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS‐IV may become a novel therapeutic medicine for SCI.

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“…The inflammatory response to primary structural changes in the spinal cord is accompanied by the release of a large number of regulatory peptides, including proinflammatory ones, and cytokines [ 20 , 21 ]. Cytokines are synthesized by activated macro- and microglia, damaged vascular endothelium, as well as the immune system cells mobilized from the systemic circulation to the injury site and the adjacent areas, due to changes in the BBB permeability [ 22 ].…”

Section: Immune and Cytokine Responses During The Acute Post-traummentioning

confidence: 99%

Cytokine profile as a marker of cell damage and immune dysfunction after spinal cord injury

et al. 2020

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This study reviews the findings of recent experiments designed to investigate the cytokine profile after a spinal cord injury. The role played by key cytokines in eliciting the cellular response to trauma was assessed. The results of the specific immunopathogenetic interaction between the nervous and immune systems in the immediate and chronic post-traumatic periods are summarized. It was demonstrated that it is reasonable to use the step-by-step approach to the assessment of the cytokine profile after a spinal cord injury and take into account the combination of the pathogenetic and protective components in implementing the regulatory effects of individual cytokines and their integration into the regenerative processes in the injured spinal cord. This allows one to rationally organize treatment and develop novel drugs.

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Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

Cited by 54 publications

References 253 publications

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Cytokine profile as a marker of cell damage and immune dysfunction after spinal cord injury

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