Int J Biol Sci 2020; 16(12):2042-2050. doi:10.7150/ijbs.45467

Review

Role of Pyroptosis in Traumatic Brain and Spinal Cord Injuries

Xinli Hu1,2*, Huanwen Chen3*, Hui Xu1,2, Yaosen Wu1,2, Chenyu Wu1,2, Chang Jia4, Yao Li1,2, Sunren Sheng1,2, Cong Xu1,2, Huazi Xu1,2, Wenfei Ni1,2✉, Kailiang Zhou1,2✉

1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
2. Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China
3. University of Maryland School of Medicine, Baltimore, MD 21201, USA
4. Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
*These authors contributed equally to this work.

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Citation:
Hu X, Chen H, Xu H, Wu Y, Wu C, Jia C, Li Y, Sheng S, Xu C, Xu H, Ni W, Zhou K. Role of Pyroptosis in Traumatic Brain and Spinal Cord Injuries. Int J Biol Sci 2020; 16(12):2042-2050. doi:10.7150/ijbs.45467. Available from http://www.ijbs.com/v16p2042.htm

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Abstract

Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), remains a leading cause for morbidity and mortality worldwide. Past research has shown that cell death plays a critical role in the pathophysiology of CNS injuries. More recently, pyroptosis has been identified as a form of programmed inflammatory cell death, and it is a unique form of cell death in various aspects. Mechanistically, pyroptosis can be categorized into canonical (mediated by caspase-1) and non-canonical (mediated by caspase-4/5/11). In canonical pyroptosis, Nod-like receptors (NLRs) inflammasomes play a critical role, and their activation promotes the maturation and secretion of the inflammatory cytokines interleukin-1β/18 (IL-1β/18), cleavage of gasdermin D (GSDMD), and ultimately pyroptotic cell death. Despite a plethora of new knowledge regarding pyroptosis, detailed understanding of how pyroptosis is involved in CNS injuries and possible ways to improve clinical outcomes following CNS injuries remain elusive. This review discusses the current knowledge on how pyroptosis is involved in CNS injuries, focusing on new discoveries regarding how pyroptosis activation occurs, differences between CNS cell types following injury, time-course of inflammatory responses, and key regulatory steps of pyroptosis. In addition, we highlight various investigational agents that are capable of regulating key steps in pyroptotic cell death, and we discuss how these agents may be used as therapies to improve outcomes following CNS trauma.

Keywords: Pyroptosis, Traumatic brain injury, Spinal cord injury, Inflammasomes, Cell death