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脑外伤后抑制神经炎症的疗法。

Therapies negating neuroinflammation after brain trauma.

作者信息

Hellewell Sarah, Semple Bridgette D, Morganti-Kossmann Maria Cristina

机构信息

Canadian Military and Veterans׳ Clinical Rehabilitation Research Program, Faculty of Rehabilitation Medicine, University of Alberta, 3-48 Corbett Hall, Edmonton, AB, Canada T6G 2G4.

Melbourne Brain Centre, Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Melbourne, Australia.

出版信息

Brain Res. 2016 Jun 1;1640(Pt A):36-56. doi: 10.1016/j.brainres.2015.12.024. Epub 2015 Dec 29.

Abstract

Traumatic brain injury (TBI) elicits a complex secondary injury response, with neuroinflammation as a crucial central component. Long thought to be solely a deleterious factor, the neuroinflammatory response has recently been shown to be far more intricate, with both beneficial and detrimental consequences depending on the timing, magnitude and specific immune composition of the response post-injury. Despite extensive preclinical and clinical research into mechanisms of secondary injury after TBI, no effective neuroprotective therapy has been identified, with potential candidates repeatedly proving disappointing in the clinic. The neuroinflammatory response offers a promising avenue for therapeutic targeting, aiming to quell the deleterious consequences without influencing its function in providing a neurotrophic environment supportive of repair. The present review firstly describes the findings of recent clinical trials that aimed to modulate inflammation as a means of neuroprotection. Secondly, we discuss promising multifunctional and single-target anti-inflammatory candidates either currently in trial, or with ample experimental evidence supporting clinical application. This article is part of a Special Issue entitled SI:Brain injury and recovery.

摘要

创伤性脑损伤(TBI)引发复杂的继发性损伤反应,神经炎症是关键的核心组成部分。长期以来,神经炎症反应一直被认为只是一个有害因素,但最近的研究表明,它要复杂得多,根据损伤后反应的时间、程度和特定免疫组成,其既有有益的后果,也有有害的后果。尽管对TBI后继发性损伤的机制进行了广泛的临床前和临床研究,但尚未确定有效的神经保护疗法,潜在的候选药物在临床上反复令人失望。神经炎症反应为治疗靶点提供了一条有前景的途径,旨在消除有害后果,同时不影响其在提供支持修复的神经营养环境中的功能。本综述首先描述了近期旨在调节炎症作为神经保护手段的临床试验结果。其次,我们讨论了目前正在试验或有充分实验证据支持临床应用的有前景的多功能和单靶点抗炎候选药物。本文是名为“SI:脑损伤与恢复”的特刊的一部分。

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