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

Abstract

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.

Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord

“…Metabolic failure further contributes to this ionic and oxidative disturbance [ 52 , 53 ]. Damage to the blood-spinal cord barrier (BSCB) disturbs its protective function and allows unregulated migration of inflammatory cells and cytokines into the area to perpetuate the local inflammatory response, contributing to local spinal cord oedema, which can in turn result in further damage [ 39 , 54 , 55 ].…”

Pyroptosis in Spinal Cord Injury: Implications for Pathogenesis and Therapeutic Approaches

“…NLRP3 begins to activate and assemble when primed cells are subjected to activation stimuli under appropriate conditions [85]. Multiple factors can act as second signals for the activation and assembly of NLRP3 after SCI, including choles-terol and ATP levels, cytoarchitectural instability such as lysosomal rupture and mitochondrial dysfunction, and ionic or molecular perturbations such as K + efflux, Ca 2+ signaling, and ROS [86]. Liu et al [87] showed that treatment of BV2 cells with an advanced oxidative protein product (AOPP) induced NLRP3 inflammasome activation and GS-DMD cleavage, leading to cleavage of caspase-1, downstream production of mature IL-1β and IL-18, and apoptosis.…”

Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications

“…As previously mentioned, the production of cytokines is linked to the activation of inflammasomes, particularly the NLRP3 inflammasome. The literature indicates that the activation of the NLRP3 inflammasome has been observed in peripheral immune cells, as well as neural cells in the CNS such as astrocytes, microglia, and infiltrated macrophages following SCI . Activated microglia can induce the infiltration of circulating macrophages to the site of injury and stimulate the expression of various proinflammatory cytokines, including IL-1α, IL-1β, and TNF-α, thereby mediating the inflammatory response .…”