The Role of Tumor Necrosis Factor Following Spinal Cord Injury: A Systematic Review

Lund, Minna Christiansen; Clausen, Bettina Hjelm; Brambilla, Roberta; Lambertsen, Kate Lykke

doi:10.1007/s10571-022-01229-0

Cited by 10 publications

(13 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunohistochemical analysis revealed that TNF was expressed by cells located in proximity to vessels, suggesting that infiltrating immune cells are major producers of TNF in the acute phase after SCI. These findings are supported by previous reports that also demonstrate TNF expression by neurons, microglia, and astrocytes, in addition to oligodendrocytes in the acute phase after SCI [ 12 , 13 , 14 , 17 , 47 ]. In the present study, we extend previous findings of increased Tnf mRNA levels in the delayed phase after SCI [ 13 ] by showing increased TNF expression from 3 to 14 days after SCI, correlating with the time points of peripheral immune cells infiltration into the injured spinal cord [ 40 ].…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, manipulating the inflammatory response after SCI may help regulate the formation of the glial scar, allowing for better axonal regrow. Besides therapeutically manipulating the inflammatory response after SCI using, i.e., anti-TNF therapeutics (reviewed by [ 17 ]), transplantation with mesenchymal stem cells can inhibit excessive glial scar formation and the inflammatory response leading to improved functional outcome (reviewed by [ 80 ]). Another promising cell therapeutic approach is the use of autologous transplantation of patient-derived induced pluripotent stem cell-derived oligodendrocyte precursor cell-enriched neural stem/progenitor cells, as preclinical SCI studies have demonstrated the positive effect of these cells on robust remyelination of demyelinated axons, resulting in improved functional recovery (reviewed by [ 81 , 82 ]).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have examined the cellular and temporal expression of TNF and its receptors in the acute phase after SCI [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, only a few studies focused on clarifying TNF expression in the delayed phase after SCI [ 11 , 13 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Diminishing detrimental neuroinflammatory processes, such as the excessive production of pro-inflammatory cytokines, is considered a possible therapeutic strategy in individuals with SCI; therefore, more detailed knowledge on the temporal and cellular synthesis of inflammatory mediators is required. TNF is believed to be one of the most promising neuroinflammatory targets in SCI [ 17 ]; therefore, this study investigated the temporal and cellular source of TNF and its two receptors in the acute and delayed phases after SCI using a moderate contusive SCI model in C57BL/6J mice. The findings were verified in postmortem tissue and cerebrospinal fluid (CSF), derived from individuals with SCI.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

Lund

Ellman

Nissen

et al. 2022

Biology

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) initiates detrimental cellular and molecular events that lead to acute and delayed neuroinflammation. Understanding the role of the inflammatory response in SCI requires insight into the temporal and cellular synthesis of inflammatory mediators. We subjected C57BL/6J mice to SCI and investigated inflammatory reactions. We examined activation, recruitment, and polarization of microglia and infiltrating immune cells, focusing specifically on tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2. In the acute phase, TNF expression increased in glial cells and neuron-like cells, followed by infiltrating immune cells. TNFR1 and TNFR2 levels increased in the delayed phase and were found preferentially on neurons and glial cells, respectively. The acute phase was dominated by the infiltration of granulocytes and macrophages. Microglial/macrophage expression of Arg1 increased from 1–7 days after SCI, followed by an increase in Itgam, Cx3cr1, and P2ry12, which remained elevated throughout the study. By 21 and 28 days after SCI, the lesion core was populated by galectin-3+, CD68+, and CD11b+ microglia/macrophages, surrounded by a glial scar consisting of GFAP+ astrocytes. Findings were verified in postmortem tissue from individuals with SCI. Our findings support the consensus that future neuroprotective immunotherapies should aim to selectively neutralize detrimental immune signaling while sustaining pro-regenerative processes.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

Lund

Ellman

Nissen

et al. 2022

Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…TNF is another pivotal cytokine released after SCI onset, as increased TNF expression has been demonstrated throughout the acute and chronic stages of SCI in the resident cells of spinal tissue. TNF inhibitors, such as adalimumab, infliximab, and etanercept, promoted functional recovery after SCI ( 122 ). Yuan et al.…”

Section: Inhibiting the Inflammasome Pathwaysmentioning

confidence: 99%

An emerging role of inflammasomes in spinal cord injury and spinal cord tumor

Chen

Shen²,

Shao³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Spinal cord injury (SCI) and spinal cord tumor are devastating events causing structural and functional impairment of the spinal cord and resulting in high morbidity and mortality; these lead to a psychological burden and financial pressure on the patient. These spinal cord damages likely disrupt sensory, motor, and autonomic functions. Unfortunately, the optimal treatment of and spinal cord tumors is limited, and the molecular mechanisms underlying these disorders are unclear. The role of the inflammasome in neuroinflammation in diverse diseases is becoming increasingly important. The inflammasome is an intracellular multiprotein complex and participates in the activation of caspase-1 and the secretion of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18. The inflammasome in the spinal cord is involved in the stimulation of immune-inflammatory responses through the release of pro-inflammatory cytokines, thereby mediating further spinal cord damage. In this review, we highlight the role of inflammasomes in SCI and spinal cord tumors. Targeting inflammasomes is a promising therapeutic strategy for the treatment of SCI and spinal cord tumors.

show abstract

System failure: Systemic inflammation following spinal cord injury

DiSabato,

Marion,

Mifflin

et al. 2023

Eur J Immunol

View full text Add to dashboard Cite

Spinal cord injury (SCI) affects hundreds of thousands of people in the United States, and while some effects of the injury are broadly recognized (deficits to locomotion, fine motor control, and quality of life), the systemic consequences of SCI are less well‐known. The spinal cord regulates systemic immunological and visceral functions, and this control is often disrupted by the injury resulting in viscera including the gut, spleen, liver, bone marrow, and kidneys experiencing local tissue inflammation and physiological dysfunction. The extent of pathology depends on the injury level, severity, and time post‐injury. In this review, we describe immunological and metabolic consequences of SCI across several organs. Since infection and metabolic disorders are primary reasons for reduced lifespan after SCI, it is imperative that research continues to focus on these deleterious aspects of SCI to improve life span and quality of life for individuals with SCI.This article is protected by copyright. All rights reserved

show abstract

The Role of Tumor Necrosis Factor Following Spinal Cord Injury: A Systematic Review

Cited by 10 publications

References 105 publications

The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

An emerging role of inflammasomes in spinal cord injury and spinal cord tumor

System failure: Systemic inflammation following spinal cord injury

Contact Info

Product

Resources

About