Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis

Mukhamedshina, Yana; Akhmetzyanova, Elvira R.; Martynova, Ekaterina; Khaiboullina, Svetlana F.; Galieva, Luisa R.; Rizvanov, Albert A.

doi:10.3389/fneur.2017.00581

Cited by 55 publications

(71 citation statements)

References 42 publications

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“…A potential explanation for this paradox is that IL-6 results in a more transient STAT3 activation, whereas IL-10 results in a more sustained activation [8], perhaps due to negative feedback from SOCS family members after IL-6 activation but not IL-10 [103]. Interestingly, expression of IL-4 and IL-10, along with most other antiinflammatory cytokines, exhibit transient and acute expression after SCI [22,46,63], which may contribute to the prevalence of M1-like macrophages that persist chronically at the injury site. Accordingly, exogenous administration of IL-4 can promote M2-like polarization that is associated with improved histopathology and behavioral outcomes [22].…”

Section: Transcriptional Regulation Of Macrophage Polarizationmentioning

confidence: 99%

The origin, fate, and contribution of macrophages to spinal cord injury pathology

2019

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Virtually all phases of spinal cord injury pathogenesis, including inflammation, cell proliferation and differentiation, as well as tissue remodeling are mediated in part by infiltrating monocytederived macrophages. It is now clear these infiltrating macrophages have distinct functions from resident microglia, and are capable of mediating both harmful and beneficial effects after injury. These divergent effects have been largely attributed to environmental cues, such as specific cytokines, that influence the macrophage polarization state. In this review, we also consider the possibility that different macrophage origins, including the spleen, bone marrow, and local selfrenewal, may also affect macrophage fate, and ultimately their function that contribute to the complex pathobiology of spinal cord injury.

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Section: Transcriptional Regulation Of Macrophage Polarizationmentioning

confidence: 99%

The origin, fate, and contribution of macrophages to spinal cord injury pathology

2019

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“…When compared to sham conditions, spinal cords from SCI mice had significantly increased levels of IL-10 in comparison to 4 days, 5 days, and 7 days sham conditions (one-way ANOVA, Bonferroni's multiple comparisons test; * * * p < 0.001, * * p < 0.005, * * p < 0.005, respectively. As a positive control, we tested cuprizone-treated mice (a model of multiple sclerosis), which are known to secrete proinflammatory cytokines at the end of 5 weeks of treatment (Mukhamedshina et al, 2017). Cuprizone-treated mice showed expected increases in levels of TNF-α, IL-1β, and IL-10 in comparison to naïve controls (one-way ANOVA, Bonferroni's multiple comparisons test; * p < 0.05, * * p < 0.005, * * p < 0.005, respectively; Schmitz and Chew, 2008).…”

Section: Characterization Of Behavioral and Inflammatory Phenotypes Omentioning

confidence: 99%

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Yasko

Moss

Mains

2019

Front. Mol. Neurosci.

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Traumatic spinal cord injury (SCI) has devastating implications for patients, including a high predisposition for developing chronic pain distal to the site of injury. Chronic pain develops weeks to months after injury, consequently, patients are treated after irreparable changes have occurred. Nociceptors are central to chronic pain; however, the diversity of this cellular population presents challenges to understanding mechanisms and attributing pain modalities to specific cell types. To begin to address how peripheral sensory neurons below the injury level may contribute to the below-level pain reported by SCI patients, we examined SCI-induced changes in gene expression in lumbar dorsal root ganglia (DRG) below the site of injury. SCI was performed at the T10 vertebral level, with injury produced by a vessel clip with a closing pressure of 15 g for 1 min. Alterations in gene expression produce long-term sensory changes, therefore, we were interested in studying SCI-induced transcripts before the onset of chronic pain, which may trigger changes in downstream signaling pathways and ultimately facilitate the transmission of pain. To examine changes in the nociceptor subpopulation in DRG distal to the site of injury, we retrograde labeled sensory neurons projecting to the hairy hindpaw skin with fluorescent dye and collected the corresponding lumbar (L2-L6) DRG 4 days post-injury. Following dissociation, labeled neurons were purified by fluorescenceactivated cell sorting (FACS). RNA was extracted from sorted sensory neurons of naïve, sham, or SCI mice and sequenced. Transcript abundances validated that the desired population of nociceptors were isolated. Cross-comparisons to data sets from similar studies confirmed, we were able to isolate our cells of interest and identify a unique pattern of gene expression within a subpopulation of neurons projecting to the hairy hindpaw skin. Differential gene expression analysis showed high expression levels and significant transcript changes 4 days post-injury in SCI cell populations relevant to the onset of chronic pain. Regulatory interrelationships predicted by pathway analysis implicated changes within the synaptogenesis signaling pathway as well as networks related to inflammatory signaling mechanisms, suggesting a role for synaptic plasticity and a correlation with pro-inflammatory signaling in the transition from acute to chronic pain.

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“…During acute phase, SC expresses high amounts of Th1 phenotype which is mainly regulated by IL-2, IL-12 and IFNy. Moreover, in subacute phases IL-4, IL-13, IL-10, IL-17 and IL-23 cytokines are found in plasma and spleen, indicating the presence of Th2, Treg and Th17 profiles as an inefficient compensatory mechanism [93,94]. Accordingly to this, for the last 10 years experimental findings have shown that T lymphocytes are not just pathogenic but beneficial.…”

Section: Lymphocytes As Double-edged Sword In Spinal Cord Injurymentioning

confidence: 92%

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

Rodríguez-Barrera¹,

Soria-Zavala²,

García–Sánchez³

et al. 2019

Spinal Cord Injury Therapy [Working Title]

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Spinal cord injury (SCI) involves damage to the spinal cord causing both structural and functional changes, which can lead to temporary or permanent alterations. Even though there have been many advances in its treatment, the results of clinical trials suggest that the current therapies are not sufficiently effective.Recently, there has been a lot of interest in regulating this harmful environment by transplanting cultured cells and boosting their antiinflammatory cytokines and growth factors production. Several types of cells have been studied for SCI therapy including, Schwann cells (SC's), olfactory ensheathing cells (OECs), choroid plexus epithelial cells (CPECs), and immune cells (ICs) (lymphocytes, dendritic cells and alternative macrophage and microglia phenotypes). These treatments have shown to be promising and in this chapter, we will review the general aspects of transplanting these cells for SCI therapy as well as the neuroprotective and regenerative responses that different types of cells have reached in different SCI models. The mesenchymal stem cells (MSC) are one of the most well studied cell types; however, they were not included in this section because they will be reviewed in another chapter of this book.

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Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis

Cited by 55 publications

References 42 publications

The origin, fate, and contribution of macrophages to spinal cord injury pathology

The origin, fate, and contribution of macrophages to spinal cord injury pathology

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

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