Australian School of Advanced Medicine, Macquarie University Sydney, NSW, Australia.
Front Neurol. 2013 Mar 4;4:18. doi: 10.3389/fneur.2013.00018. eCollection 2013.
Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia, and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (Interleukin-1, Tumor Necrosis Factor, Interleukin-6), the anti-inflammatory cytokines (IL-4, Interleukin-10, and TGF-beta), and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following Traumatic brain injury (TBI), the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring, and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality, or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This review article will discuss the evidence from both clinical and laboratory studies exploring the validity of immune markers as a correlate to classification and outcome following TBI.
创伤发生后的几分钟内，受伤大脑会引发强烈的炎症反应。这种创伤后炎症反应非常复杂，涉及到细胞成分，包括驻留神经胶质细胞、小胶质细胞和星形胶质细胞的激活，以及血液白细胞的浸润。第二个成分涉及免疫介质的分泌，这些介质可以分为以下亚群：典型的促炎细胞因子（白细胞介素-1、肿瘤坏死因子、白细胞介素-6）、抗炎细胞因子（IL-4、白细胞介素-10 和 TGF-β）以及趋化细胞因子或趋化因子，它们专门驱动实质和外周免疫细胞在受伤的大脑区域聚集。这些机制在动物模型中得到了证实，主要是在啮齿类动物中，也在人类大脑中得到了证实。虽然体液免疫反应在创伤性脑损伤（TBI）后急性期特别明显，但胶质细胞的激活似乎是一种持续数月的延长效应。细胞因子和细胞类型的复杂相互作用安装了一个事件网络，随后与相邻的病理级联交叉，包括氧化应激、兴奋毒性或修复事件，包括血管生成、瘢痕形成和神经发生。人们普遍认为神经炎症是有益和有害影响的原因，导致继发性脑损伤，但也促进神经修复。尽管这些介质是免疫激活的明显标志物，但细胞因子在多大程度上可以定义为反映脑损伤的诊断因素或作为长期预后的预测因素，还需要进一步证实。在临床研究中，一些研究小组报告说，在初始脑损伤、死亡率或预后评分较差时，脑脊液或脑实质组织中存在成比例的细胞因子产生。然而，细胞因子作为生物标志物的有效性并没有得到广泛认可。本文综述了来自临床和实验室研究的证据，探讨了免疫标志物作为 TBI 分类和预后相关性的有效性。
