Okada Takeshi, Suzuki Hidenori
Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.
Neural Regen Res. 2017 Feb;12(2):193-196. doi: 10.4103/1673-5374.200795.
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor (NF)-κB signaling among TLR4 signaling pathways as to the development of early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways NF-κB and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.
神经炎症是蛛网膜下腔出血（SAH）公认的后果，Toll样受体（TLR）4可能是SAH后神经炎症的一个重要治疗靶点。在TLR家族成员中，TLR4在中枢神经系统的多种细胞类型中表达，其独特之处在于它可以通过髓样分化初级反应蛋白88依赖性和干扰素依赖性级联反应的Toll受体相关激活剂发出信号，以协调最大的炎症反应。TLR4可被许多具有损伤相关分子模式的内源性配体激活，包括颅内动脉瘤破裂时的血红素和纤维蛋白原，由此产生的炎症反应以及组织损伤可能进一步激活TLR4。人们普遍认为，TLR4信号传导的分泌产物会改变神经元功能。先前的研究集中在TLR4信号通路中的核因子（NF）-κB信号通路与早期脑损伤（EBI）的发展，如神经元凋亡、血脑屏障破坏和脑血管痉挛之间的关系上。然而，许多研究结果表明，NF-κB和丝裂原活化蛋白激酶这两条信号通路都可能参与EBI和脑血管痉挛的发展。克服EBI和脑血管痉挛对于改善SAH后的预后很重要，因为EBI和血管痉挛都是导致延迟性脑损伤或延迟性脑缺血的原因，而延迟性脑缺血是SAH后不良预后的最重要可预防原因。越来越多的证据表明，TLR4信号传导在SAH诱导的脑损伤中起重要作用。更好地理解TLR4信号传导在SAH中的作用将有助于开发新的治疗方法。
