Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as "secondary injury." Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follow TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states toward a stimulus- and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

中文翻译：

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外伤性脑损伤的神经免疫学：范式转变的时间。

颅脑外伤（TBI）是发病率和残疾的主要原因，并具有相当大的社会经济负担。病理解剖亚型的异质性以及致病机理和损伤程度的多样性导致了TBI病程和预后的差异。在原发性伤害之后，通过一系列复杂的事件（称为“继发性伤害”）持续遭受广泛而持久的伤害。在动物和人类研究中，神经炎症被认为是继发性损伤的重要可操作方面。由于神经发炎可能有害或有益，因此在制定免疫调节疗法之前，有必要更好地了解TBI后免疫反应的时机和复杂性。随着文学的迅速增长，需要对TBI神经免疫学有一个清晰的总结。这篇综述提出了我们目前对TBI免疫反应的理解，以时间顺序和基于隔室的方式，强调了基因表达的早期变化和导致固有免疫和适应性免疫激活的初始信号通路。基于对先天免疫细胞激活的最新理解，我们提出了一种新的范式来研究TBI后的先天免疫细胞，它从现有的激活状态的M1 / M2分类转变为对极化状态的刺激和疾病特异性理解基于转录和蛋白质组分析。强调了基因表达和初始信号通路的早期变化，这些变化导致先天免疫和适应性免疫的激活。基于对先天免疫细胞激活的最新理解，我们提出了一种新的范式来研究TBI后的先天免疫细胞，它从现有的激活状态的M1 / M2分类转变为对极化状态的刺激和疾病特异性理解基于转录和蛋白质组分析。强调了基因表达和初始信号通路的早期变化，这些变化导致先天免疫和适应性免疫的激活。基于对先天免疫细胞激活的最新理解，我们提出了一种新的范式来研究TBI后的先天免疫细胞，它从现有的激活状态的M1 / M2分类转变为对极化状态的刺激和疾病特异性理解基于转录和蛋白质组分析。