Role of necroptosis in traumatic brain and spinal cord injuries

Traumatic brain injury (TBI) and spinal cord injury (SCI) are capable of causing severe sensory, motor and autonomic nervous system dysfunctions. However, effective treatments for TBI and SCI are still unavailable, mainly because the death of nerve cells is uncontrollable. Necroptosis is a type of programmed cell death and a critical mechanism in the process of neuronal cell death. However, the role of necroptosis has not been comprehensively defined in TBI and SCI. This review aimed to summarize the role of necroptosis in central nervous system (CNS) trauma and its therapeutic implications and present important suggestions for researchers conducting in-depth research. Necroptosis is orchestrated by a complex comprising the receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) proteins. Mechanistically, RIPK1 and RIPK3 form a necrosome with MLKL. After MLKL dissociates from the necrosome, it translocates to the plasma membrane to induce pore formation in the membrane and then induces necroptosis. In this review, the necroptosis signalling pathway and the execution of necroptosis are briefly discussed. In addition, we focus on the existing information on the mechanism by which necroptosis participates in CNS trauma, particularly in the temporal pattern of RIPKs and in different cell types. Furthermore, we describe the association of miRNAs and necroptosis and the relationship between different types of CNS trauma cell death. Finally, this study highlights agents likely capable of curtailing such a type of cell death according to results optimization and CNS trauma and presents important suggestions for researchers conducting in-depth research.