Skip to main content
Download PDF

Modulation of inflammatory factors predicts the outcome following spinal cord injury

Journal of Orthopaedic Surgery and Research volume 15, Article number: 199 (2020) Cite this article

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 day 10 to day 30.

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 preliminarily 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.

Background

Spinal cord injury (SCI) caused by trauma often leads to the disruption of axonal tracts, being the third most common cause of acquired disability worldwide [1, 2]. After the initial traumatic insult, the cascade reaction of blood supply reduction, oxidation, and inflammation following SCI leads to neurological disorders, including the destruction of the blood-spinal cord barrier, neuroinflammation, and oxidative stress [3, 4]. Inflammation in the early stage of SCI promotes the recovery of the injured spinal cord, and prematurely, glial scar or inflammation inhibition might lead to more serious damage to the injured spinal cord [5]. It is believed that different phenotypes of inflammatory cells play critical roles in neuroprotection. Neuroinflammation occurs almost immediately after spinal cord injury, including the activation of immune cells and cytokines [6]. Studies have demonstrated that mast cells, bone marrow-derived macrophages, dendritic cells, type 2 innate lymphocytes (ILC2s), and T cells might influence the outcome of spinal cord injury [7,8,9,10,11]. These cells release a large number of inflammatory factors (IL-1, IL-6, IL-8, IL-12, IFN-α, IFN-γ), chemokines (CXCL-1, CXCL-2), proteolytic enzymes, and complement proteins when damage occurs [12, 13]. Among these cytokines, the pro-inflammatory mediators, reactive oxygen species, and nitric oxide (NO) often contribute to inflammation and aggravate the traumatic injury [14]. On the contrary, the interleukin (IL)-4, IL-10, and IL-13 are pro-regenerative cytokines which can contribute to tissue repair, wound healing, and promote axons regeneration [15,16,17].

At present, spinal cord injury in rats is the most commonly used model in animal experiments of SCI, and the Basso-Beattie-Bresnahan (BBB) score is the most commonly used behavioral index to evaluate the recovery of lower limb motor function after SCI, which is also the most widely used evaluation standard of lower limb motor function in the world [18, 19]. The BBB locomotor rating scale is a 21-point scale, which was originally used in SCI rat models; it has high sensitivity, good test-retest reliability, and strong validity [19, 20]. Inter-rater reliability tests show that examiners with different experiences in behavioral tests can consistently use the scale and get similar scores [19]. The BBB score included almost all the behavioral changes of rats during the recovery of lower limb motor function after SCI, which was highly consistent with the degree of SCI.

Despite therapeutic strategies and imaging diagnostic techniques have improved dramatically in the past decades, the prognostic evaluation of SCI still depends on computed tomography (CT), magnetic resonance imaging (MRI), and the physical examination of neurological functions [21, 22]. Few studies have examined proinflammatory cytokines and immune cells to evaluate the prognosis of patients with SCI. In the current study, we evaluated the prognostic value of the serum IL-4 and IL-10 expression and observed the inflammatory cells of the injured spinal cord in predicting the prognosis of neurological function in patients with SCI.

Materials and methods

Animal breeding

Thirty-two male Sprague-Dawley rats, aged 6~8 weeks, weighing 220–250 g, were housed in the Laboratory Animal Centre of Nanjing Medical University in accordance with the animal experimental guidelines set by and with the approval of the National Institute of Health and the Nanjing Medical University.

SCI procedures

The rats were intraperitoneally injected with 1% pentobarbital sodium (50 mg/kg). The model of SCI was established as previously described [23]. Briefly, the spinous process and the vertebral lamina were removed to expose the spinal cord in a circular region at the T10 level. A graduated force of 70 g was placed over the exposed dura and left for 60 s to induce a compression injury. The rat models of SCI should meet the following characteristics to make sure all the models were in a similar base level, including congestive edema of T10 segment, twitch of the tail and hindlimb, and neurogenic bladder. Each rat was feed separately, and the bladder of rats was given artificial massage twice a day until a reflex bladder emptying was established. Sham-operated mice received laminectomy without compression injury.

Basso-Beattie-Bresnahan score

Lower limb motor function was evaluated using the BBB score, as previously described by Basso et al. [24]. The rats were placed in an open field and two independent; blinded examiners observed these rats for 10 minutes individually. The rats were tested at days 5, 10, 15, 20, 25, and 30 post-SCI surgery. In brief, the BBB scores of hindlimb motor function of SCI rats ranged from 0 (complete paralysis) to 21 (unimpaired locomotion), in which 0–7 mainly evaluated the movement of the hindlimb joints, 8–13 mainly evaluated the gait and coordination of the hindlimbs, and 14–21 mainly evaluated the fine movements of the claws in the movement [19, 20].

Study design

The motor function of the lower limbs in all rats was evaluated using the BBB score after SCI operation at days 5, 10, 15, 20, 25, and 30, but the three rats with the highest BBB score (BBB high group) and the three with the lowest BBB score (BBB low group) were executed at days 10, 20, and 30. Therefore, the BBB high group always had three rats with the highest BBB score, and the BBB low group always had three rats with the lowest BBB score in every BBB score testing. The spinal cord tissues of the executed rats were removed and used for immunofluorescence detection in the BBB high group and BBB low group at days 10, 20, and 30, respectively.

Serum evaluation

Blood samples were taken from the eyeballs of all surviving rats for serum evaluation at days 5, 10, 15, 20, 25, and 30. Serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I, and inducible nitric oxide synthase (iNOS) were detected using enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. The final concentrations of IL-4, IL-10, MHC-I, and iNOS were interpolated from the determined standard curve of absorbance. After discovering that there may be some kind of pattern, we further compared serum IL-4 and IL-10 levels of the three rats with the highest BBB score (BBB high group) and the three with the lowest BBB score (BBB low group) at days 5, 10, 15, and 30, respectively.

Immunofluorescence

Spinal cord tissues were deparaffinized and rehydrated in coronal sections (4 μm thickness); then, the sections were blocked with 5% bovine serum albumin at room temperature for 30 min and then washed with PBS three times for 10 min. The sections were then incubated with corresponding primary antibodies overnight at 4 °C, including F4/80, iNOS, arginase (Arg)1, and NF200 (Invitrogen, Carlsbad, CA, USA), and incubated with secondary antibody (1:500; Abcam, Shanghai, China) for 3 h. The slides were visualized using a fluorescence microscope (Olympus BX 51, Tokyo, Japan), and ImageJ (Wayne Rasband, National Institutes of Health, Bethesda, MD, USA) was used for quantitative analysis.

Statistical analysis

All data were presented as mean ± standard error of mean (SEM) and were analyzed by two-way ANOVA repeated measurement using SPSS Statistics 20.0 (SPSS Inc., Chicago, IL, USA) for statistical significance. A P value < 0.05 was considered statistically significant.

Results

The change of cytokines in serum is related to the prognosis

The SCI model was successfully established and all rats survived and were included in the statistical analysis. Our findings suggested that the lower limb motor function of rats gradually recovered following SCI, and the BBB score increased significantly during follow up (Fig. 1). Elisa revealed that the levels of serum IL-4, IL-10, MHC-I, and iNOS grew steadily from day 5 to day 30 after SCI, among which, the fold changes of IL-4 and IL-10 were the most obvious (Fig. 2). Therefore, we speculated that serum levels of IL-4 and IL-10 might change in rats with different prognoses. Ulteriorly, we compared the serum levels of IL-4 and IL-10 in the BBB high group and BBB low group, and we found that the serum levels of IL-4 and IL-10 in the BBB high group were significantly higher than those in the BBB low group (Fig. 3). These results suggested that IL-4 and IL-10 might be effective cytokines for predicting the prognosis of SCI, which needs further experiments to confirm.

Fig. 1
figure 1

BBB scores of rats following SCI over time

Full size image
Fig. 2
figure 2

The serum levels of cytokines (IL-4, IL-10, MHC-I, and iNOS) were quantified by ELISA over time following SCI

Full size image
Fig. 3
figure 3

Comparison of serums IL-4 and IL-10 in the BBB high group and BBB low group. The serum levels of IL-4 (a) and IL-10 (b) were significantly higher in the BBB high group. *P < 0.05, **P < 0.01, as compared with the BBB high group

Full size image

The polarization of macrophage predicts the prognosis of SCI

Macrophage plays a critical role in the inflammatory response following SCI; therefore, the macrophage polarization was analyzed. F4/80 is a definite marker of macrophages. iNOS indicates that macrophages polarize to M1, and Arg1 indicates that macrophages polarize to M2. Immunofluorescence showed the F4/80 expression increased significantly from day 10 to day 30, indicating that the infiltration of macrophage in the injured spinal cord increased along with the time after SCI (Fig. 4a–c). Besides, the fluorescence intensity of Arg1 was upregulated, and iNOS was downregulated markedly from day 10 to day 30, indicating that macrophages polarize from M1 to M2 along with the time following SCI. Additionally, the fluorescence intensity of Arg1 in the BBB high group was significantly higher than that in the BBB low group (Fig. 4d). These results indicate that the upregulation of the M2 subtype of macrophage may predict a better prognosis following SCI.

Fig. 4
figure 4

Polarized macrophages were observed by immunofluorescence following SCI. The number of macrophages in the damaged spinal cord rose dramatically at day 10 (a), day 20 (b), and day 30 (c) after SCI. The M2 subtype of macrophage in the BBB high group is significantly higher than that in the BBB low group from day 10 to day 30 following SCI (d). *P < 0.05, **P < 0.01, as compared with the BBB high group

Full size image

The axonal regrowth was activated after SCI

Axon regeneration promotes lower limb motor function after spinal cord injury in rats. To observe axonal regeneration in spinal cord tissue, NF200 was determined by immunofluorescence. NF200 is a specific marker of axonal regeneration. Our findings suggested that the fluorescence intensity of NF200 increased significantly from day 10 to day 30, indicating that axon regeneration increased along with the time following SCI (Fig. 5a–c). Besides, the fluorescence intensity of NF200 was upregulated markedly from day 10 to day 30, indicating that fluorescence intensity of NF200 in the BBB high group was significantly higher than that in the BBB low group (Fig. 5d).

Fig. 5
figure 5

Axons were observed by immunofluorescence following SCI. The number of axons in the injured spinal cord increased at day 10 (a), day 20 (b), and days 30 (c) following SCI. The reborn axons in the BBB high group were markedly increased from day 20 to day 30 following SCI (d). *P < 0.05, **P < 0.01, as compared with the BBB high group

Full size image

Discussion

Auxiliary examinations such as imaging and electrophysiological examinations are frequently used to evaluate SCI severity but fail to predict the prognosis [25, 26]. Therefore, a quantitative index must be established to allow the objective evaluation of SCI severity and prognosis. An inflammatory response at the injured spinal cord leads to compress within the vertebral column and results in secondary damage [27,28,29]. The pro-inflammatory cytokines such as MHC-I and nitric oxide (NO) all contribute to inflammation and tissue damage [30]. By contrast, the pro-regenerative cytokines including IL-4 and IL-10 contribute to wound healing and tissue repair and enhance regrowth of axons [31]. However, few studies have explored their roles in assessing SCI severity in rats with spine trauma.

The BBB score is an effective evaluation method for the recovery of lower limb motor function after spinal cord injury. A higher BBB score indicates better prognosis. In the present study, a compression injury of the spinal cord was successfully established in rats, and we found that the BBB score increased over time, indicating that the lower limb motor function of rats gradually recovered following SCI. Interestingly, we found that the serum levels of IL-4, IL-10, MHC-I, and iNOS grew steadily from day 5 to day 30 following SCI, especially the fold changes of IL-4 and IL-10 exhibit the most obvious. To explore the difference of cytokines between a high BBB score and low BBB score, 3 rats with the highest BBB score and the 3 with the lowest BBB score were selected at day 10, day 20, and day 30. We found that the serum levels of IL-4 and IL-10 in rats with high BBB scores were significantly higher than those in rats with low BBB scores, indicating that serums IL-4 and IL-10 might be effective cytokines for predicting the prognosis of SCI. To observe the inflammation and axon regeneration of the injured spinal cord at the pathological level, the protein expression of F4/80, iNOS, Arg1, and NF200 were assessed by immunofluorescence. F4/80 is a definite marker of macrophages [32]. iNOS indicates that macrophages polarize to M1, and Arg1 indicates that macrophages polarize to M2 [33]. NF200 is a skeletal structure of neural cells and axons, a specific marker of axonal regeneration, which can reflect the degree of axonal regeneration in the spinal cord of rats after SCI [34]. Our findings suggested that the expression of F4/80 was increased following SCI, suggesting that macrophages were infiltrated in the injured spinal cord. As time went on and with the increasing of BBB score, Arg1 expression increased, while iNOS decreased, suggesting that macrophages polarized from M1 to M2. Besides, NF200 expression increased significantly over, indicating that axon regeneration increased following SCI. Moreover, the fluorescence intensity of NF200 was upregulated effectively over time, indicating that axon regeneration in rats with high BBB scores was significantly higher than that in rats with low BBB scores.

Anti-inflammatory cytokines play a critical role in axon regeneration following SCI. In the neuroinflammatory microenvironment, the pro-inflammatory cytokines are cytotoxic to neurons, which lead to extend short neurite sprouts after SCI [15, 35]. IL-10 has been demonstrated to upregulate anti-apoptotic factors such as B cell lymphoma 2 (Bcl-2) and provide a direct trophic influence on neurons to improve the neurotoxic microenvironment [36, 37]. IL-4 in the SCI phase reduces the release of pro-inflammatory factors at the impaired spinal cord [38, 39]. Moreover, IL-10 has shown to induce the expression of IL-4R, and stimulate M2 subtype of macrophages to produce both IL-10 and IL-4, which may create a feed-forward process at the injured spinal cord site [17, 40]. As previous studies have demonstrated a change from M1 to M2 is an essential part of the repair process, and polarization of macrophages from M1 to M2 may contribute to a better axon regeneration and prognosis [41,42,43].

Conclusions

Collectively, the current study demonstrates that the serum levels of IL-4 and IL-10 are preliminarily 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. There might be some correlations between serum IL-4, IL-10, and macrophage polarization in regulating axon regeneration, and the potential mechanisms need further exploration.

Availability of data and materials

Research data can be obtained from the corresponding authors upon reasonable request.

Abbreviations

Arg:

Arginase

BBB:

Basso-Beattie-Bresnahan

Bcl-2:

B cell lymphoma 2

CT:

Computed tomography

ELISA:

Enzyme-linked immunosorbent assay

IL-10:

Interleukin-10

IL-4:

Interleukin-4

ILC2s:

Type 2 innate lymphocytes

iNOS:

Inducible nitric oxide synthase

MHC-I:

Major histocompatibility complex-I

MRI:

Magnetic resonance imaging

NO:

Nitric oxide

SCI:

Spinal cord injury

SEM:

Standard error of mean

References

  1. Silva NA, et al. From basics to clinical: a comprehensive review on spinal cord injury. Prog Neurobiol. 2014;114:25–57.

    Article  Google Scholar 

  2. Young M, et al. Time-related changes in quality of life in persons with lower limb amputation or spinal cord injury: protocol for a systematic review. Syst Rev. 2019;8(1):191.

    Article  Google Scholar 

  3. Zhang D, et al. The neuroprotective effect of puerarin in acute spinal cord injury rats. Cell Physiol Biochem. 2016;39(3):1152–64.

    Article  CAS  Google Scholar 

  4. He J, et al. Molecular mechanism of MiR-136-5p targeting NF-κB/A20 in the IL-17-mediated inflammatory response after spinal cord injury. Cell Physiol Biochem. 2017;44(3):1224–41.

    Article  CAS  Google Scholar 

  5. Chio JCT, et al. The effects of human immunoglobulin G on enhancing tissue protection and neurobehavioral recovery after traumatic cervical spinal cord injury are mediated through the neurovascular unit. J Neuroinflammation. 2019;16(1):141.

    Article  Google Scholar 

  6. Kigerl KA, McGaughy VM, Popovich PG. Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J Comp Neurol. 2006;494(4):578–94.

    Article  Google Scholar 

  7. Vangansewinkel T, et al. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6. FASEB J. 2016;30(5):2040–57.

    Article  CAS  Google Scholar 

  8. Wang L, et al. Myeloid-derived suppressor cells mediate immune suppression in spinal cord injury. J Neuroimmunol. 2016;290:96–102.

    Article  CAS  Google Scholar 

  9. Yaguchi M, et al. Transplantation of dendritic cells promotes functional recovery from spinal cord injury in common marmoset. Neurosci Res. 2009;65(4):384–92.

    Article  Google Scholar 

  10. Gadani, S.P. and I. Smirnov, Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury. 2017. 214(2): p. 285-296.

  11. Sun G. And S. Yang, γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury. 2018;215(2):521–35.

  12. Park J, et al. Nerve regeneration following spinal cord injury using matrix metalloproteinase-sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor. J Biomed Mater Res A. 2010;93(3):1091–9.

    PubMed  Google Scholar 

  13. Chen Z, et al. Mitigation of sensory and motor deficits by acrolein scavenger phenelzine in a rat model of spinal cord contusive injury. J Neurochem. 2016;138(2):328–38.

    Article  CAS  Google Scholar 

  14. Kim DK, et al. Ginsenoside Rg3 improves recovery from spinal cord injury in rats via suppression of neuronal apoptosis, pro-inflammatory mediators, and microglial activation. Molecules. 2017;22(1):122.

    Article  Google Scholar 

  15. David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 2011;12(7):388–99.

    Article  CAS  Google Scholar 

  16. Martinez, F.O. and S. Gordon, The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 2014. 6: p. 13.

  17. Mantovani A, et al. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013;229(2):176–85.

    Article  CAS  Google Scholar 

  18. Song RB, et al. Adaptation of the Basso-Beattie-Bresnahan locomotor rating scale for use in a clinical model of spinal cord injury in dogs. J Neurosci Methods. 2016;268:117–24.

  19. Basso DM, Beattie MS, Bresnahan JC. A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in Rats. J Neurotrauma. 1995;12(1):1–21.

  20. DM Basso, et al. MASCIS Evaluation of Open Field Locomotor Scores: Effects of Experience and Teamwork on Reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma. 1996;13(7):343–59.

  21. Frontera JE, Mollett P. Aging with spinal cord injury: an update. Phys Med Rehabil Clin N Am. 2017;28(4):821–8.

    Article  Google Scholar 

  22. Talbott JF, et al. MR imaging for assessing injury severity and prognosis in acute traumatic spinal cord injury. Radiol Clin N Am. 2019;57(2):319–39.

    Article  Google Scholar 

  23. Peter C Poon, et al. Clip Compression Model Is Useful for Thoracic Spinal Cord Injuries: Histologic and Functional Correlates. Spine (Phila Pa 1976). 2007;32(25):2853–9.

  24. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1–21.

    Article  CAS  Google Scholar 

  25. Ahuja CS, et al. Spinal cord injury-what are the controversies? J Orthop Trauma. 2017;31(Suppl 4):S7–s13.

    Article  Google Scholar 

  26. Skeers P, et al. Acute thoracolumbar spinal cord injury: relationship of cord compression to neurological outcome. J Bone Joint Surg Am. 2018;100(4):305–15.

    Article  Google Scholar 

  27. David S, Lopez-Vales R, Wee Yong V. Harmful and beneficial effects of inflammation after spinal cord injury: potential therapeutic implications. Handb Clin Neurol. 2012;109:485–502.

    Article  Google Scholar 

  28. Park J, et al. Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury. J Neurochem. 2015;135(5):987–97.

    Article  CAS  Google Scholar 

  29. Due MR, et al. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat. J Neurochem. 2014;128(5):776–86.

    Article  CAS  Google Scholar 

  30. He FY, et al. Effects of propofol and dexmedetomidine anesthesia on Th1/Th2 of rat spinal cord injury. Eur Rev Med Pharmacol Sci. 2017;21(6):1355–61.

    PubMed  Google Scholar 

  31. Lima R, et al. Systemic Interleukin-4 administration after spinal cord injury modulates inflammation and promotes neuroprotection. Pharmaceuticals (Basel). 2017;10(4):83.

    Article  Google Scholar 

  32. Kiguchi N, et al. Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists suppresses spinal microglial activation and neuropathic pain in mice with peripheral nerve injury. J Neuroinflammation. 2018;15(1):96.

    Article  Google Scholar 

  33. Zhang Y, et al. Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages. J Neurosci Res. 2019;97(7):733–43.

    Article  CAS  Google Scholar 

  34. M K Lee, et al. Neurofilaments Are Obligate Heteropolymers in Vivo. J Cell Biol. 1993;122(6):1337–50.

  35. Kigerl KA, et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29(43):13435–44.

    Article  CAS  Google Scholar 

  36. Thompson CD, et al. The therapeutic role of interleukin-10 after spinal cord injury. J Neurotrauma. 2013;30(15):1311–24.

    Article  Google Scholar 

  37. Zhou Z, et al. Interleukin-10 provides direct trophic support to neurons. J Neurochem. 2009;110(5):1617–27.

    Article  CAS  Google Scholar 

  38. Bhattacharjee A, et al. IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages. Free Radic Biol Med. 2013;54:1–16.

    Article  CAS  Google Scholar 

  39. Garcia E, et al. Cytokine and growth factor activation in vivo and in vitro after spinal cord injury. Mediat Inflamm. 2016;2016:9476020.

    Google Scholar 

  40. Margul DJ, et al. Reducing neuroinflammation by delivery of IL-10 encoding lentivirus from multiple-channel bridges. Bioeng Transl Med. 2016;1(2):136–48.

    Article  CAS  Google Scholar 

  41. Miron VE, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16(9):1211–8.

    Article  CAS  Google Scholar 

  42. Miron VE, Franklin RJ. Macrophages and CNS remyelination. J Neurochem. 2014;130(2):165–71.

    Article  CAS  Google Scholar 

  43. Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res. 2015;1619:1–11.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

None.

Funding

This project was supported by the Scientific Research Topics of Jiangsu Provincial Health Commission (No. H2018027), the Science and Education to Promote Health of Suzhou (KJXW2016034), and the Suzhou Science and Technology Development Plan Project (SYSD2018146).

Author information

Author notes

  1. Zepeng Yu and Xingwei Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China

    Zepeng Yu & Xingwei Sun

  2. Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China

    Rui Xia

  3. Department of Oncology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215008, People’s Republic of China

    Qian Chen

  4. Department of Ultrasonography, Suzhou Science and Technology Town Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215001, People’s Republic of China

    Qin Wu

  5. Department of Orthopaedics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215008, People’s Republic of China

    Weiwei Zheng

Authors
  1. Zepeng Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xingwei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weiwei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Zepeng Yu and Xingwei Sun proposed the study and wrote the first draft. Qian Chen and Rui Xia analyzed the data. Weiwei Zheng and Qin Wu contributed to the design of the study. The authors read and approved the final manuscript.

Corresponding authors

Correspondence to Qin Wu or Weiwei Zheng.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the ethics committee of The Second Affiliated Hospital of Soochow University.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Z., Sun, X., Xia, R. et al. Modulation of inflammatory factors predicts the outcome following spinal cord injury. J Orthop Surg Res 15, 199 (2020). https://doi.org/10.1186/s13018-020-01727-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13018-020-01727-1

Keywords

Journal of Orthopaedic Surgery and Research

ISSN: 1749-799X