Spinal cord injury induces a long-lasting upregulation of interleukin-1β in astrocytes around the central canal

Paniagua‐Torija, Beatriz; Arévalo-Martı́n, Ángel; Molina‐Holgado, Eduardo; Molina-Holgado, Francisco; Garcı́a-Ovejero, Daniel

doi:10.1016/j.neuroscience.2014.10.013

Cited by 13 publications

(14 citation statements)

References 46 publications

(60 reference statements)

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“…Since the pro-inflammatory cytokines TNF-α and IL-1β have been associated with central neuropathic pain after spinal cord injury 33 – 35 , we also assessed whether their expression in spinal cord is attenuated in σ 1 R KO mice 28 days after injury. The ANOVA analysis revealed significant differences between groups in both TNF-α and IL-1β expression (p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…Pro-inflammatory cytokines play a major role in neuron–glia cross-talk in neuroinflammatory processes but they also play a role in pain and central sensitization phenomena in the context of neuropathic pain 33 – 35 , 45 , 68 – 77 . In particular, spinal TNF-α and IL-1β are involved in mechanisms underlying the development and maintenance of neuropathic pain by promoting synaptic plasticity and central sensitization.…”

Section: Discussionmentioning

confidence: 99%

“…As a mechanistic correlate, given the role of σ 1 R in modulating central sensitization phenomena 14 , 30 , we also investigated phosphorylation in the spinal cord of the glutamate N -methyl-D-aspartate (NMDA) receptor and the extracellular signal-regulated kinase (ERK1/2); both of which are reportedly involved in central sensitization 19 and hypersensitivity in neuropathic pain conditions 31 , 32 . Moreover, considering the role of pro-inflammatory cytokines in the pathophysiology of neuropathic pain after SCI, the expression of TNF-α and IL-1β 33 – 35 was investigated.…”

Section: Introductionmentioning

confidence: 99%

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Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Castany

Gris

Vela

et al. 2018

Sci Rep

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Sigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) – a model of central neuropathic pain. The modulatory effect of σ1R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ1R KO mice following SCI. Accordingly, treatment of WT mice with the σ1R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ1R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Castany

Gris

Vela

et al. 2018

Sci Rep

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“…Reactive astrogliosis is a common response of astrocytes to most Central Nervous System (CNS) injury 1 , 2 . The prevailing dogma of the involvement of reactive astrocytes in inhibition of axonal regeneration 3 , has been challenged by recent findings of Anderson et al .…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals Neuroprotective aspects of Human Reactive Astrocytes induced by Interleukin 1β

Teh

Prasad

Jiang

et al. 2017

Sci Rep

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Reactive astrogliosis is a critical process in neuropathological conditions and neurotrauma. Although it has been suggested that it confers neuroprotective effects, the exact genomic mechanism has not been explored. The prevailing dogma of the role of astrogliosis in inhibition of axonal regeneration has been challenged by recent findings in rodent model’s spinal cord injury, demonstrating its neuroprotection and axonal regeneration properties. We examined whether their neuroprotective and axonal regeneration potentials can be identify in human spinal cord reactive astrocytes in vitro. Here, reactive astrogliosis was induced with IL1β. Within 24 hours of IL1β induction, astrocytes acquired reactive characteristics. Transcriptome analysis of over 40000 transcripts of genes and analysis with PFSnet subnetwork revealed upregulation of chemokines and axonal permissive factors including FGF2, BDNF, and NGF. In addition, most genes regulating axonal inhibitory molecules, including ROBO1 and ROBO2 were downregulated. There was no increase in the gene expression of “Chondroitin Sulfate Proteoglycans” (CSPGs’) clusters. This suggests that reactive astrocytes may not be the main CSPG contributory factor in glial scar. PFSnet analysis also indicated an upregulation of “Axonal Guidance Signaling” pathway. Our result suggests that human spinal cord reactive astrocytes is potentially neuroprotective at an early onset of reactive astrogliosis.

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“…IL-1β and its receptors are upregulated in astrocytes and microglia after spinal cord injury, with IL-1β mRNA peak expression occurring 12 hours after injury [17]. In addition, in mice, under systemic morphine administration, expression level of IL-1β is signi cantly increased, resulting in a marked decline in spinal motor function while intrathecal injection of IL-1β receptor antagonists can block the adverse effects of morphine on the recovery of spinal cord motor function [8].…”

Section: Discussionmentioning

confidence: 99%

Interference of interleukin-1β mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K/AKT signaling pathway

Wang

et al. 2020

Preprint

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Background: Spinal cord contusion (SCC) results in a series of pathophysiologic consequences such as edema, apoptosis, and inflammation. However, inflammation may also be beneficial for the recovery of motor function after SCC, but the underlying mechanisms remain incompletely elucidated. Interleukin-1 beta (IL-1β) is a pro-inflammatory factor that has synergistic effects with other inflammatory factors to aggravate spinal cord injury. Inflammatory factors have been found to activate the serine/threonine-specific protein kinase, protein kinase B (AKT) and to inhibit cell survival, but it is not clear whether inflammation upregulates the expression of IL-1β in the rat model of SCC and subsequently interferes in the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway. Therefore, this study explored whether IL-1β affects the recovery of motor function in spinal cord injury by interfering with the PI3K/AKT signaling pathway. Method: SCC rats were established by the Allen method. The Basso Beattie Bresnahan (BBB) scoring was used to assess motor function in the spinal cord of injured rats. Quantitative polymerase chain reaction and Western blot were used to determine the expression of genes and proteins of IL-1β, PI3K, and AKT1. Immunohistochemistry and immunofluorescence were used to locate and detect IL-1β and AKT1 proteins in spinal cord tissue. To further explore the underlying mechanism of IL-1β, lentivirus was constructed by RNA interfering (RNAi) technique to inhibit the expression of IL-1β, and bioinformatics was applied to show the relationship between IL-1β and AKT1. Results: BBB scores decreased after SCC, and IL-1β and AKT1 was located in the cytoplasm of spinal cord anterior horn neurons. In the early stage of SCC, the expression level of IL-1β gene and protein in the experimental group was higher than that in the sham operated group. At the same time, expression of the AKT1 gene decreased. After expression of IL-1β mediated by lentivirus was inhibited, BBB scores increased significantly, and spinal cord motor function improved. Bioinformatic analysis revealed a relationship between IL-1β and AKT1. In addition, AKT1 gene expression was upregulated and PI3K expression was unchanged in the PI3K/AKT signaling pathway. Conclusion IL-1β not only exacerbates the inflammatory response after SCC, but also interferes with motor function. Inhibition of IL-1β may promote recovery of spinal cord injury by upregulating AKT1 in the PI3K/AKT signaling pathway, which provides a new perspective for future clinical practice in treating spinal cord injury

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Spinal cord injury induces a long-lasting upregulation of interleukin-1β in astrocytes around the central canal

Cited by 13 publications

References 46 publications

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Transcriptome Analysis Reveals Neuroprotective aspects of Human Reactive Astrocytes induced by Interleukin 1β

Interference of interleukin-1β mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K/AKT signaling pathway

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