From the Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland (RG, MPS-P); and Division of Neuroscience, Oregon National Primate Research Center, Beaverton (SGK), Oregon.
J Neuropathol Exp Neurol. 2014 May;73(5):378-86. doi: 10.1097/NEN.0000000000000068.
Toll-like receptors (TLRs) are master regulators of innate immunity and play an integral role in the activation of inflammatory response during infections. In addition, TLRs influence the body's response to numerous forms of injury. Recent data have shown that TLRs play a modulating role in ischemic brain damage after stroke. Interestingly, their stimulation before ischemia induces a tolerant state that is neuroprotective. This phenomenon, referred to as TLR preconditioning, is the result of the reprogramming of TLR response to ischemic injury. This review addresses the role of TLRs in brain ischemia and the activation of endogenous neuroprotective pathways in the setting of preconditioning. We highlight the protective role of interferon-related response and the potential site of action for TLR preconditioning involving the blood-brain barrier. Pharmacologic modulation of TLR activation to promote protection against stroke is a promising approach for the development of prophylactic and immediate therapies targeting ischemic brain injury.
toll 样受体 (TLRs) 是先天免疫的主要调节剂，在感染期间炎症反应的激活中发挥着重要作用。此外，TLRs 还影响着机体对多种形式损伤的反应。最近的数据表明，TLRs 在中风后的缺血性脑损伤中起调节作用。有趣的是，在缺血前刺激 TLR 会诱导一种具有神经保护作用的耐受状态。这种现象被称为 TLR 预处理，是 TLR 对缺血性损伤反应的重新编程的结果。这篇综述讨论了 TLR 在脑缺血以及预处理情况下内源性神经保护途径的激活中的作用。我们强调了干扰素相关反应的保护作用，以及 TLR 预处理涉及血脑屏障的潜在作用机制。通过药理学调节 TLR 的激活以促进对中风的保护是开发针对缺血性脑损伤的预防性和即刻治疗的有前途的方法。
