J Neuroinflammation 2011 ;8 134. [IF:5.785]
Toll-like receptors in cerebral ischemic inflammatory injury.
Wang YC , Lin S , Yang QW .
Department of Neurology, Daping Hospital, Third Military Medical University, Changjiang Branch Road No, 10, Yuzhong District, Chongqing 400042, PR China. yangqwmlys@hotmail.com.
重庆市第三军医大学，大坪医院神经内科
Abstract
ABSTRACT: Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the innate immune system, particularly in regard to the signaling mechanisms of Toll-like receptors (TLRs), whose primary role is the initial activation of immune cell responses. So far, few studies have examined the role of TLRs in cerebral ischemia. However, work with experimental models of ischemia suggests that TLRs are involved in the enhancement of cell damage following ischemia, and their absence is associated with lower infarct volumes. It may be possible that therapeutic targets could be designed to modulate activities of the innate immune system that would attenuate cerebral brain damage. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Interpreting the molecular mechanism of ischemic tolerance will open investigative avenues into the treatment of cerebral ischemia. In this review, we discuss the critical role of TLRs in mediating cerebral ischemic injury. We also summarize evidence demonstrating that cerebral preconditioning downregulates pro-inflammatory TLR signaling, thus reducing the inflammation that exacerbates ischemic brain injury.
摘要
脑缺血引起急性炎症已经与大脑损伤的增加相联系。脑缺血后炎症反应的调控机制是多方面的。这种反应的一个重要组成就是天然免疫系统的激活。然而，一系列复杂的与脑缺血机制相联系的天然免疫系统角色的细节仍然不清楚。在我们理解天然免疫系统的进程中现在已经有了巨大的进步，特别是关于Toll-like受体的信号传导机制，Toll-like受体的主要作用就是免疫细胞反应的初始活化。迄今为止，很少有研究调查Toll-like受体在脑缺血中的角色。但是，缺血实验模型的工作意味着Toll-like受体参与缺血后细胞损伤的放大，并且，缺少他们与较低的梗死体积相关。也许能够设计治疗靶点用作调节天然免疫系统的活动，这可能减少大脑损伤。缺血耐受是一个由多种预处理刺激诱导的保护机制。缺血耐受的分子机制的解释将会打开脑缺血治疗的研究道路。在这篇综述中，我们讨论了Toll-like受体在调解脑缺血性损伤中极其重要的作用。我们也总结证据证明大脑的预处理能抑制促炎性的Toll-like受体发出信号，因此减少使缺血大脑损伤加剧的炎症。
