Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, 3086, Australia.
J Neuroinflammation. 2020 Apr 6;17(1):104. doi: 10.1186/s12974-020-01778-5.
There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.
颅脑创伤（TBI）的临床治疗需求主要在于确定潜在机制、相关生物标志物和治疗靶点。神经炎症是 TBI 的核心病理生理特征。NLRP3 炎性小体的活性是组织损伤固有免疫反应的必要组成部分，而失调的炎性小体活性与许多神经疾病有关。本文介绍了 NLRP3 炎性小体及其在神经炎症相关疾病发病机制中的作用，特别是 TBI。尽管其在 TBI 中的作用最近才被发现，但研究结果表明，TBI 后 NLRP3 炎性小体的启动和激活被上调。此外，最近利用特定 NLRP3 抑制剂的研究进一步证明，该炎性小体是 TBI 后神经炎症和神经行为障碍的主要驱动因素。此外，有新的证据表明，循环炎性小体相关蛋白可能作为神经炎症疾病的诊断生物标志物，包括 TBI。最后，还将重点介绍一些新的有前途的研究领域，包括 NLRP3 炎性小体在轻度 TBI 中的潜在作用、生物性别等因素如何影响 TBI 中的 NLRP3 活性，以及新兴生物标志物平台的应用。综上所述，本文强调了 NLRP3 炎性小体作为治疗靶点和生物标志物的巨大潜力，这可能最终有助于改善 TBI 的治疗效果。
