scholarly journals Modulation of inflammatory factors predicts the outcome following spinal cord injury

2020 ◽  
Author(s):  
Zepeng Yu ◽  
Xingwei Sun ◽  
Rui Xia ◽  
Qian Chen ◽  
Qin Wu ◽  
...  

Abstract BACKGROUND: The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial.METHODS: In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I and inducible nitric oxide synthase (iNOS), and compared the serum IL-4 and IL-10 expression in rats of high Basso-Beattie-Bresnahan (BBB) scores with these of low BBB scores. Besides, the infiltration of macrophage and the axonal regeneration of the injured spinal cord were observed from day10 to day30.RESULTS: We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of the M2 subtype of macrophage and the axons regrowth might contribute to a better prognosis.CONCLUSIONS:The current study demonstrates that the serum levels of IL-4 and IL-10 are preliminary adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.

2020 ◽  
Author(s):  
Zepeng Yu ◽  
Xingwei Sun ◽  
Rui Xia ◽  
Qian Chen ◽  
Qin Wu ◽  
...  

Abstract BACKGROUND : The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial. METHODS : In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I and inducible nitric oxide synthase (iNOS), and compared the serum IL-4 and IL-10 expression in rats of high BBB scores with these of low Basso-Beattie-Bresnahan(BBB) scores. Besides, the infiltration of macrophage and the axonal regeneration of the injuried spinal cord were observed from day10 to day30. RESULTS : We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of M2 subtype of macrophage and the axons regrowth might contribute to better prognosis. CONCLUSIONS : Collectively, the current study demonstrates that the serum levels of IL-4 and IL-10 are preliminary adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.


2015 ◽  
Vol 3 (3) ◽  
pp. 453-462
Author(s):  
Ya-Yun Shi

Spinal cord injury induces a robust neuroinflammatory response that includes marked changes in the variety of endogenous CNS cell types specially microglia. In response to spinal injury, microglia undergo dramatic changes in cell morphology and promote inflammatory responses, which result in production of inflammatory factors and oxidative stress including reactive oxygen species. Further pro-inflammatory cytokines and chemokines are also rapidly up-regulated and likely contribute to microglial activation. This topic review will explore the current research on microglial responses to spinal injury and the recent progress in the pharmacologic and molecular targeting of microglia in spinal injury. Finally, we explore the argument for a positive versus negative role of microglia after spinal cord injury.


Author(s):  
Ali Rismanbaf ◽  
Khashayar Afshari ◽  
Mehdi Ghasemi ◽  
Abolfazl Badripour ◽  
Arvin Haj-Mirzaian ◽  
...  

Abstract Background Inflammatory responses, including macrophages/microglia imbalance, are associated with spinal cord injury (SCI) complications. Accumulating evidence also suggests an anti-inflammatory property of azithromycin (AZM). Material and Methods Male Wistar rats were subjected to T9 vertebra laminectomy. SCI was induced by spinal cord compression at this level with an aneurysmal clip for 60 seconds. They were divided into three groups: the sham-operated group and two SCI treatment (normal saline as a vehicle control vs. AZM at 180 mg/kg/d intraperitoneally for 3 days postsurgery; first dose: 30 minutes after surgery) groups. Locomotor scaling and behavioral tests for neuropathic pain were evaluated and compared through a 28-day period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes and neural demyelination using ELISA and histopathologic examinations, respectively. In addition, the proportion of M1/M2 macrophage polarization was assessed by using flow cytometry. Results Post-SCI AZM treatment (180 mg/kg/d for 3 days) significantly improved locomotion (p < 0.01) and decreased sensitivity to mechanical (p < 0.01) and thermal allodynia (p < 0.001). Moreover, there was a significant tumor necrosis factor-α (TNF-α) decline (p < 0.01) and interleukin-10 (IL-10) elevation (p < 0.01) in the spinal cord tissue of the AZM-treated group compared with the control groups 28 days post-SCI. AZM significantly improved neuroinflammation as evidenced by reduction of the M1 expression, elevation of M2 macrophages, and reduction of the M1/M2 ratio in both the dorsal root ganglion and the spinal cord tissue after SCI compared with controls (p < 0.01). Conclusion AZM treatment can be considered a therapeutic agent for SCI, as it could reduce neuroinflammation and SCI sensory/locomotor complications.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangqi Lin ◽  
Baokun Zhang ◽  
Qiang Shi ◽  
Jiaming Liang ◽  
Xin Wang ◽  
...  

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Wang ◽  
Benson O. A. Botchway ◽  
Xuehong Liu

Spinal cord injury (SCI) often results in abnormal sensory and motor functions. Current interventions for SCI in the clinical setting are not effective partly due to the complexity concerning its pathophysiological mechanism. In the wake of SCI, considerable inflammatory cells assemble around the injured area that induces a series of inflammatory reactions and aggravates tissue lesions, thereby affecting the recovery of the damaged nerve tissue. Therefore, the inhibition of inflammatory responses can improve the repair of the injured spinal cord tissue. Safflower Yellow (SY) is the main active ingredient of Carthamus tinctorius. SY has anti-inflammatory effect, as it can inhibit IκBα phosphorylation to impede the NF-κB signaling pathway and p53 nuclear translocation. Besides, SY can limit the release of pro-inflammatory factors, which in turn may alleviate secondary SCI and prevent further complications. In this report, we analyze the pathophysiological mechanism of SCI, the role of inflammatory responses, and how SY interferes with the HMGB1-TLR-4-NF-κB signaling pathway to attenuate inflammatory responses in SCI.


2020 ◽  
Vol 34 (9) ◽  
pp. 12147-12162
Author(s):  
Tengfei Zhao ◽  
Kan Xu ◽  
Qionghua Wu ◽  
Chenggui Wang ◽  
Shining Xiao ◽  
...  

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.


2009 ◽  
Vol 12 (9) ◽  
pp. 1106-1113 ◽  
Author(s):  
Laura Taylor Alto ◽  
Leif A Havton ◽  
James M Conner ◽  
Edmund R Hollis II ◽  
Armin Blesch ◽  
...  

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