The far-reaching scope of neuroinflammation after traumatic brain injury.
The far-reaching scope of neuroinflammation after traumatic brain injury.
复制标题
DOI：
10.1038/nrneurol.2017.13
复制
发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Kochanek PM
中科院分区：
文献类型：
--
作者：
Simon DW;McGeachy MJ;Bayır H;Clark RS;Loane DJ;Kochanek PM
创伤性脑损伤（TBI）的“沉默流行病”已被置于聚光灯下的调查和流行的新闻报道的运动员和返回的士兵与单一和重复性损伤;然而，治疗，以改善整个范围内的TBI患者的结果从轻度到重度TBI是缺乏的。神经炎症可引起TBI后的急性继发性损伤，并且它与慢性神经退行性疾病有关。尽管有这些发现，抗炎药未能改善临床试验的结果。因此，我们在这篇综述中提出了一个新的框架，为未来探索TBI后的靶向免疫调节，纳入因素，如从受伤的时间，损伤的机制，并在考虑潜在的治疗方案的二次损伤。围绕TBI免疫反应的动力学结构-从初始触发到慢性神经炎症-可溶性和细胞炎症介质促进修复和再生与继发性损伤和神经变性的能力被强调，从人类研究中获得的知识在整个综述中明确定义。在神经免疫学和TBI反应性神经炎症的最新进展，包括炎症小体，小胶质细胞极化的机制，和胶质淋巴清除。此外，我们在整个审查中确定这些发现可能为转化和临床研究提供新的治疗靶点，纳入其他脑损伤模型的证据，并确定该领域的突出问题。
The “silent epidemic” of traumatic brain injury (TBI) has been placed in the spotlight following investigations and popular press coverage of athletes and returning soldiers with single and repetitive injuries; however, treatments to improve the outcome for patients with TBI across the spectrum from mild to severe TBI are lacking. Neuroinflammation may cause acute secondary injury after TBI, and it has been linked to chronic neurodegenerative diseases. Despite these findings, anti-inflammatory agents have failed to improve outcomes in clinical trials. We therefore propose in this review a new framework for future exploration of targeted immunomodulation after TBI that incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structured around the dynamics of the immune response to TBI – from initial triggers to chronic neuroinflammation – the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration is highlighted, with knowledge from human studies explicitly defined throughout this review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. In addition, we identify throughout this review where these findings may offer novel therapeutic targets for translational and clinical research, incorporate evidence from other brain injury models, and identify outstanding questions in the field.
登录
查看更多内容
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
影响因子：
2.5
作者：
BELLINGER, FP;MADAMBA, SG;SIGGINS, GR
通讯作者：
SIGGINS, GR
影响因子：
4.2
作者：
Bellander, BM;Singhrao, SK;Svensson, M
通讯作者：
Svensson, M
影响因子：
4.1
作者：
Bullock, R;Zauner, A;Young, HF
通讯作者：
Young, HF
影响因子：
--
作者：
Bandak, F A;Ling, G;De Lanerolle, N C
通讯作者：
De Lanerolle, N C