Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Br J Pharmacol. 2010 Aug;160(8):1872-88. doi: 10.1111/j.1476-5381.2010.00864.x.
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and complement, chemokines and adhesion molecules that recruit immune cells, and activate glia and microglia. Cerebral ischaemia triggers acute inflammation, which exacerbates primary brain damage. The regulation of inflammation after stroke is multifaceted and comprises vascular effects, distinct cellular responses, apoptosis and chemotaxis. There are many cell types that are affected including neurons, astrocytes, microglia and endothelial cells, all responding to the resultant neuroinflammation in different ways. Over the past 20 years, researchers examining brain tissue at various time intervals after stroke observed the presence of inflammatory cells, neutrophils and monocytes at the site of injury, as well as the activation of endogenous glia and microglia. This review examines the involvement of these cells in the progression of neural injury and proposes that the Toll-like receptors (TLRs) are likely to be an integral component in the communication between the CNS and the periphery. This receptor system is the archetypal pathogen sensing receptor system and its presence and signalling in the brain following neural injury suggests a more diverse role. We propose that the TLR system presents excellent pharmacological targets for the design of a new generation of therapeutic agents to modulate the inflammation that accompanies neural injury.
中枢神经系统（CNS）在应对损伤、感染或疾病时可能会表现出炎症特征，其中驻留细胞会产生炎症介质，包括细胞因子、前列腺素、自由基和补体、趋化因子和黏附分子，这些物质可以招募免疫细胞，并激活神经胶质细胞和小胶质细胞。脑缺血会引发急性炎症，从而加重原发性脑损伤。中风后炎症的调节是多方面的，包括血管效应、不同的细胞反应、细胞凋亡和趋化作用。许多细胞类型受到影响，包括神经元、星形胶质细胞、小胶质细胞和内皮细胞，它们都以不同的方式对由此产生的神经炎症做出反应。在过去的 20 年中，研究人员在中风后不同时间间隔检查脑组织时观察到损伤部位有炎症细胞（中性粒细胞和单核细胞）以及内源性神经胶质细胞和小胶质细胞的激活。这篇综述探讨了这些细胞在神经损伤进展中的作用，并提出 Toll 样受体（TLR）可能是中枢神经系统与外周之间通讯的一个重要组成部分。该受体系统是典型的病原体感应受体系统，其在神经损伤后的大脑中的存在和信号转导表明它具有更多样的作用。我们提出，TLR 系统为设计新一代治疗药物以调节伴随神经损伤的炎症提供了极好的药理学靶点。
