Abstract
Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), is characterized by high morbidity, disability, and mortality. TBI and SCI have similar pathophysiological mechanisms and are often accompanied by serious inflammatory responses. Pyroptosis, an inflammation-dependent programmed cell death, is becoming a major problem in CNS post-traumatic injury. Notably, the pyrin domain containing 3 (NLRP3) inflammasome is a key protein in the pyroptosis signaling pathway. Therefore, underlying mechanism of the NLRP3 inflammasome in the development of CNS trauma has attracted much attention. In this review, we briefly summarize the molecular mechanisms of NLRP3 inflammasome in pyroptosis signaling pathway, including its prime and activation. Moreover, the dynamic expression pattern, and roles of the NLRP3 inflammasome in CNS post-traumatic injury are summarized. The therapeutic applications of NLRP3 inflammasome activation inhibitors are also discussed.
Highlights
Central nervous system (CNS) traumatic diseases, including spinal cord injury (SCI) and traumatic brain injury (TBI), are characterized by a high disability rate and various complications, and some hypotheses propose that high disability and mortality rates occur because of secondary injury development
Activation of the NLRP3 inflammasome is a central link in pyroptosis and is involved in the pathological development of various inflammatory diseases, including SCI and TBI
The current treatment of NLRP3 pathology is still limited to animal experiments and is even more restricted to the canonical pyroptosis pathway
Summary
Central nervous system (CNS) traumatic diseases, including spinal cord injury (SCI) and traumatic brain injury (TBI), are characterized by a high disability rate and various complications, and some hypotheses propose that high disability and mortality rates occur because of secondary injury development. As a response of the innate immune system in the CNS, neuroinflammation plays a key role in the second stage of TBI and SCI, of which the most important step is the activation of the various inflammasome complexes (Zhou et al, 2016). Excessive neuroinflammation tends to hinder repair and regeneration, and the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation appears to be responsible for the unfavorable outcome in CNS injury. Activation of the NLRP3 inflammasome is the key to pyroptosis and the trigger of the inflammatory response, which plays an important role in the pathogenesis of various inflammatory diseases (Mangan et al, 2018). The role of the NLRP3 inflammasome in CNS trauma still remains complex and controversial. The pharmacological applications of NLRP3 inflammasome inhibitors in CNS trauma are discussed
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