Scholz Martin, Cinatl Jindrich, Schädel-Höpfner Michael, Windolf Joachim
Klinik für Unfall-und Handchirurgie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Med Res Rev. 2007 May;27(3):401-16. doi: 10.1002/med.20064.
Despite the fact that neutrophils are essential for the protection from invading pathogens, hyperactive neutrophils may elicit detrimental cerebral damage after severe trauma. The neutrophil interactions with the neurovascular unit entail endothelial dysfunction involving endothelial leakage, formation of edema, coagulation abnormalities, disturbed hemodynamics, tissue infiltration etc. These elements of the "whole body inflammation," designated systemic inflammatory response syndrome (SIRS) in conjunction with intracerebral proinflammatory activities, are important triggers of post-traumatic cerebral damage and mortality according to the "second hit" concept. From the immunologic point of view, the brain is an immune privileged site, known to resist autodestructive inflammatory activity much more efficiently than other organs because of the highly efficient diverse functions of the blood-brain barrier (BBB). However, both the underlying strategy of the BBB to maintain cerebral protecting functions against the post-traumatic neutrophil-mediated "second hit" and how activated neutrophils may overcome the BBB are currently unknown. Therefore, this review summarizes the current understanding of the "second hit," the BBB physiology, and its role in the maintenance of cerebral immune privilege, and discusses recent findings that may explain the pathophysiologic neutrophil-BBB interactions occurring after severe trauma, thus offering novel therapeutic options to protect from post-traumatic brain damage.
尽管中性粒细胞对于抵御入侵病原体至关重要，但在严重创伤后，过度活跃的中性粒细胞可能引发有害的脑损伤。中性粒细胞与神经血管单元的相互作用会导致内皮功能障碍，包括内皮渗漏、水肿形成、凝血异常、血流动力学紊乱、组织浸润等。根据“二次打击”概念，这些“全身炎症”的要素，即与脑内促炎活动相关的全身炎症反应综合征（SIRS），是创伤后脑损伤和死亡的重要触发因素。从免疫学角度来看，大脑是一个免疫特权部位，由于血脑屏障（BBB）具有高效多样的功能，已知其比其他器官更能有效抵抗自身破坏性炎症活动。然而，目前尚不清楚血脑屏障维持脑保护功能以对抗创伤后中性粒细胞介导的“二次打击”的潜在策略，以及活化的中性粒细胞如何突破血脑屏障。因此，本综述总结了目前对“二次打击”、血脑屏障生理学及其在维持脑免疫特权中的作用的理解，并讨论了可能解释严重创伤后发生的病理生理中性粒细胞 - 血脑屏障相互作用的最新发现，从而为预防创伤后脑损伤提供新的治疗选择。
