scholarly journals The Role of Interleukins after Spinal Cord Injury

2021 ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Rylie M. Roddick ◽  
Sophia M. Mauney ◽  
Ryan T. Elder ◽  
Carolyn N. Morehouse ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Cord Injury ◽  
Anti Inflammatory

In skin wound healing the injured tissue goes through a normal progression, inflammation subsides and remodeling occurs. However after spinal cord injury inflammation persists and there is less progression into a regenerative/rebuilding phase. This inflammatory process after spinal cord injury is orchestrated by many cell types and numerous cytokines. Although there are several positive effects of inflammation after spinal cord injury, such as the removal of debris, the substantial upregulation of immune cells has been shown to contribute to neural degeneration. Several chemokines and cytokines including many interleukins are involved in guiding these immune cells to the lesion. While there are many inflammatory cytokines acting on these immune cells after SCI, there are also several anti-inflammatory interleukins that have shown beneficial effects in reducing inflammation. After SCI in a rat model, interleukin-10 and interleukin-19 have been shown to downregulate the synthesis of pro-inflammatory species including interleukin-1β and tumor necrosis factor-α, which resulted in a significant improvement in rat hind limb function. Also, interleukin-4 and interleukin-13 are related anti-inflammatory cytokines that regulate many aspects of inflammation and have also been shown to induce alternative macrophage activation. The differing and complex roles interleukins play, highlight their importance on the inflammation that persists after spinal cord injury. Here we review both the positive effects and negative effects that interleukins have during the multifaceted inflammation process following spinal cord injury.

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

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract 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.

scholarly journals Schwann Cell Transplantation Subdues the Pro-Inflammatory Innate Immune Cell Response after Spinal Cord Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2550 ◽  
Author(s):  
Damien Pearse ◽  
Johana Bastidas ◽  
Sarah Izabel ◽  
Mousumi Ghosh
Keyword(s):  
Spinal Cord ◽  
Flow Cytometry ◽  
Spinal Cord Injury ◽  
Immune Cells ◽  
Innate Immune ◽  
Injured Spinal Cord ◽  
Multicolor Flow Cytometry ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Cluster Of Differentiation

The transplantation of Schwann cells (SCs) has been shown to provide tissue preservation and support axon growth and remyelination as well as improve functional recovery across a diverse range of experimental spinal cord injury (SCI) paradigms. The autologous use of SCs has progressed to Phase 1 SCI clinical trials in humans where their use has been shown to be both feasible and safe. The contribution of immune modulation to the protective and reparative actions of SCs within the injured spinal cord remains largely unknown. In the current investigation, the ability of SC transplants to alter the innate immune response after contusive SCI in the rat was examined. SCs were intraspinally transplanted into the lesion site at 1 week following a thoracic (T8) contusive SCI. Multicolor flow cytometry and immunohistochemical analysis of specific phenotypic markers of pro- and anti-inflammatory microglia and macrophages as well as cytokines at 1 week after SC transplantation was employed. The introduction of SCs significantly attenuated the numbers of cluster of differentiation molecule 11B (CD11b)+, cluster of differentiation molecule 68 (CD68)+, and ionized calcium-binding adapter molecule 1 (Iba1)+ immune cells within the lesion implant site, particularly those immunoreactive for the pro-inflammatory marker, inducible nitric oxide synthase (iNOS). Whereas numbers of anti-inflammatory CD68+ Arginase-1 (Arg1+) iNOS− cells were not altered by SC transplantation, CD68+ cells of an intermediate, Arg1+ iNOS+ phenotype were increased by the introduction of SCs into the injured spinal cord. The morphology of Iba1+ immune cells was also markedly altered in the SC implant, being elongated and in alignment with SCs and in-growing axons versus their amoeboid form after SCI alone. Examination of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and anti-inflammatory cytokines, interleukin-4 (IL-4) and interleukin-10 (IL-10), by multicolor flow cytometry analysis showed that their production in CD11b+ cells was unaltered by SC transplantation at 1 week post-transplantation. The ability of SCs to subdue the pro-inflammatory iNOS+ microglia and macrophage phenotype after intraspinal transplantation may provide an important contribution to the neuroprotective effects of SCs within the sub-acute SCI setting.

scholarly journals Reducing inflammation through delivery of lentivirus encoding for anti-inflammatory cytokines attenuates neuropathic pain after spinal cord injury

2018 ◽  
Vol 290 ◽  
pp. 88-101 ◽  
Author(s):  
Jonghyuck Park ◽  
Joseph T. Decker ◽  
Dominique R. Smith ◽  
Brian J. Cummings ◽  
Aileen J. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Inflammatory Cytokines ◽  
Cord Injury ◽  
Anti Inflammatory

scholarly journals Prednisolone Pretreatment Enhances Intermittent Hypoxia-Induced Plasticity in Persons With Chronic Incomplete Spinal Cord Injury

2019 ◽  
Vol 33 (11) ◽  
pp. 911-921 ◽  
Author(s):  
Milap S. Sandhu ◽  
Elizabeth Gray ◽  
Masha Kocherginsky ◽  
Arun Jayaraman ◽  
Gordon S. Mitchell ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Intermittent Hypoxia ◽  
Interleukin 10 ◽  
Voluntary Contraction ◽  
Controlled Study ◽  
Incomplete Spinal Cord Injury ◽  
Clinical Trial Registration ◽  
Cord Injury ◽  
Anti Inflammatory

Objective. To test the hypothesis that an anti-inflammatory corticosteroid drug enhances spinal motor plasticity induced by acute intermittent hypoxia (AIH) in persons with chronic incomplete spinal cord injury (iSCI). Methods. Fourteen subjects with incomplete spinal cord injury (ASIA level C or D; mean age = 46 years) participated in a randomized, double-blinded, crossover, and placebo-controlled study. Subjects received either 60 mg oral prednisolone or a matching placebo, 1 hour before administration of AIH (15, 60-second hypoxic exposures; fraction of inspired oxygen [FiO2] = 0.09). Changes in voluntary ankle strength, lower extremity electromyograms (EMG), and serum inflammatory biomarkers were quantified. Results. Maximal ankle plantarflexion torque was significantly higher following prednisolone + AIH versus placebo + AIH (mean difference [MD] 9, 11, and 7 newton meter [N∙m] at 30, 60, and 120 minutes post-AIH, respectively; all Ps <.02). Soleus surface EMG during maximal voluntary contraction was also significantly increased following prednisolone + AIH (MD 3.5, P = .02 vs placebo + AIH), while activity of other leg muscles remained unchanged. Individuals had significantly higher levels of the anti-inflammatory serum biomarker interleukin-10 after prednisolone versus placebo ( P = .004 vs placebo + AIH). Conclusions. Pretreatment with prednisolone increased the capacity for AIH-induced functional motor plasticity, suggesting that suppression of inflammation enhances the efficacy of AIH administration in individuals with spinal cord injury. Clinical trial registration number: NCT03752749.

scholarly journals Lentiviral interleukin-10 gene therapy preserves fine motor circuitry and function after a cervical spinal cord injury in male and female mice

2020 ◽  
Author(s):  
Jessica Y Chen ◽  
Emily J Fu ◽  
Paras R Patel ◽  
Hasan A Sawan ◽  
Kayla A Moss ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Interleukin 10 ◽  
Fine Motor ◽  
Behavioral Recovery ◽  
Post Injury ◽  
Cord Injury ◽  
Muscle Innervation ◽  
Anti Inflammatory

AbstractIn mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, lower motor neuron apoptosis and muscle innervation using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce lower motor neuron loss, muscle denervation, and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

scholarly journals Current Knowledge of Microglia in Traumatic Spinal Cord Injury

2022 ◽  
Vol 12 ◽  
Author(s):  
Lintao Xu ◽  
Jingyu Wang ◽  
Yueming Ding ◽  
Linlin Wang ◽  
Yong-Jian Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Microglial Activation ◽  
Neuronal Injury ◽  
Traumatic Spinal Cord Injury ◽  
Activated Microglia ◽  
Cord Injury ◽  
Anti Inflammatory

Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI.

scholarly journals Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation

2021 ◽  
Vol 8 (10) ◽  
pp. 230
Author(s):  
Tae-Kyeong Lee ◽  
Jae-Chul Lee ◽  
Hyun-Jin Tae ◽  
Hyung-Il Kim ◽  
Myoung Cheol Shin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cardiac Arrest ◽  
Inflammatory Cytokines ◽  
Motor Neurons ◽  
Anterior Horn ◽  
Motor Deficits ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Cardiac arrest (CA) causes severe spinal cord injury and evokes spinal cord disorders including paraplegia. It has been reported that risperidone, an antipsychotic drug, effectively protects neuronal cell death from transient ischemia injury in gerbil brains. However, until now, studies on the effects of risperidone on spinal cord injury after asphyxial CA (ACA) and cardiopulmonary resuscitation (CPR) are not sufficient. Therefore, this study investigated the effect of risperidone on hind limb motor deficits and neuronal damage/death in the lumbar part of the spinal cord following ACA in rats. Mortality, severe motor deficits in the hind limbs, and the damage/death (loss) of motor neurons located in the anterior horn were observed two days after ACA/CPR. These symptoms were significantly alleviated by risperidone (an atypical antipsychotic) treatment after ACA. In vehicle-treated rats, the immunoreactivities of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β), as pro-inflammatory cytokines, were increased, and the immunoreactivities of IL-4 and IL-13, as anti-inflammatory cytokines, were reduced with time after ACA/CPR. In contrast, in risperidone-treated rats, the immunoreactivity of the pro-inflammatory cytokines was significantly decreased, and the anti-inflammatory cytokines were enhanced compared to vehicle-treated rats. In brief, risperidone treatment after ACA/CPR in rats significantly improved the survival rate and attenuated paralysis, the damage/death (loss) of motor neurons, and inflammation in the lumbar anterior horn. Thus, risperidone might be a therapeutic agent for paraplegia by attenuation of the damage/death (loss) of spinal motor neurons and neuroinflammation after ACA/CPR.

scholarly journals 1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chiaki Yamada ◽  
Aiko Maeda ◽  
Katsuyuki Matsushita ◽  
Shoko Nakayama ◽  
Kazuhiro Shirozu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Cervical Vertebrae ◽  
Intractable Pain ◽  
Target Area ◽  
Positive Effects ◽  
Cord Injury

Abstract Background Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. Case presentation A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. Conclusions SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

2020 ◽  
Vol 9 (4) ◽  
pp. 1221 ◽  
Author(s):  
Jacek M. Kwiecien ◽  
Liqiang Zhang ◽  
Jordan R. Yaron ◽  
Lauren N. Schutz ◽  
Christian J. Kwiecien-Delaney ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Low Dose ◽  
Dorsal Column ◽  
Neurological Deficits ◽  
Sustained Delivery ◽  
Post Surgery ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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