Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Australian New Zealand Intensive Care Research Centre, Melbourne, VIC, Australia.
Acta Neuropathol. 2019 May;137(5):731-755. doi: 10.1007/s00401-018-1944-6. Epub 2018 Dec 7.
This review recounts the definitions and research evidence supporting the multifaceted roles of neuroinflammation in the injured brain following trauma. We summarise the literature fluctuating from the protective and detrimental properties that cytokines, leukocytes and glial cells play in the acute and chronic stages of TBI, including the intrinsic factors that influence cytokine responses and microglial functions relative to genetics, sex, and age. We elaborate on the pros and cons that cytokines, chemokines, and microglia play in brain repair, specifically neurogenesis, and how such conflicting roles may be harnessed therapeutically to sustain the survival of new neurons. With a brief review of the clinical and experimental findings demonstrating early and chronic inflammation impacts on outcomes, we focus on the clinical conditions that may be amplified by neuroinflammation, ranging from acute seizures to chronic epilepsy, neuroendocrine dysfunction, dementia, depression, post-traumatic stress disorder and chronic traumatic encephalopathy. Finally, we provide an overview of the therapeutic agents that have been tested to reduce inflammation-driven secondary pathological cascades and speculate the future promise of alternative drugs.
这篇综述回顾了神经炎症在创伤后损伤大脑中的多方面作用的定义和研究证据。我们总结了文献中关于细胞因子、白细胞和神经胶质细胞在 TBI 的急性和慢性阶段发挥的保护和有害作用，包括影响细胞因子反应和小胶质细胞功能的内在因素，这些因素与遗传、性别和年龄有关。我们详细阐述了细胞因子、趋化因子和小胶质细胞在脑修复，特别是神经发生中的利弊，以及如何在治疗上利用这些相互矛盾的作用来维持新神经元的存活。在简要回顾了临床和实验研究结果，这些结果表明早期和慢性炎症对结果有影响后，我们重点关注了可能被神经炎症放大的临床情况，从急性癫痫发作到慢性癫痫、神经内分泌功能障碍、痴呆、抑郁、创伤后应激障碍和慢性创伤性脑病。最后，我们概述了已经测试过的用于减少炎症驱动的继发性病理级联反应的治疗药物，并推测了替代药物的未来前景。
