National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, VIC 3181, Australia.
Neurotherapeutics. 2010 Jan;7(1):22-30. doi: 10.1016/j.nurt.2009.10.016.
Despite dramatic improvements in the management of traumatic brain injury (TBI), to date there is no effective treatment available to patients, and morbidity and mortality remain high. The damage to the brain occurs in two phases, the initial primary phase being the injury itself, which is irreversible and amenable only to preventive measures to minimize the extent of damage, followed by an ongoing secondary phase, which begins at the time of injury and continues in the ensuing days to weeks. This delayed phase leads to a variety of physiological, cellular, and molecular responses aimed at restoring the homeostasis of the damaged tissue, which, if not controlled, will lead to secondary insults. The development of secondary brain injury represents a window of opportunity in which pharmaceutical compounds with neuroprotective properties could be administered. To establish effective treatments for TBI victims, it is imperative that the complex molecular cascades contributing to secondary injury be fully elucidated. One pathway known to be activated in response to TBI is cellular and humoral inflammation. Neuroinflammation within the injured brain has long been considered to intensify the damage sustained following TBI. However, the accumulated findings from years of clinical and experimental research support the notion that the action of inflammation may differ in the acute and delayed phase after TBI, and that maintaining limited inflammation is essential for repair. This review addresses the role of several cytokines and chemokines following focal and diffuse TBI, as well as the controversies around the use of therapeutic anti-inflammatory treatments versus genetic deletion of cytokine expression.
尽管创伤性脑损伤 (TBI) 的治疗有了显著的改善，但迄今为止，患者仍然没有有效的治疗方法，发病率和死亡率仍然很高。脑损伤分为两个阶段，初始原发性阶段是损伤本身，这是不可逆转的，只能通过预防措施来最大限度地减少损伤程度，然后是持续的继发性阶段，从损伤时开始，并在随后的几天到几周内持续。这个延迟阶段会导致各种生理、细胞和分子反应，旨在恢复受损组织的内稳态，如果不受控制，将导致继发性损伤。继发性脑损伤的发展为具有神经保护特性的药物化合物的给药提供了机会窗口。要为 TBI 患者建立有效的治疗方法，就必须充分阐明导致继发性损伤的复杂分子级联反应。已知在对 TBI 作出反应时被激活的一条途径是细胞和体液炎症。受伤大脑内的神经炎症长期以来一直被认为会加剧 TBI 后的损伤。然而，多年的临床和实验研究的累积发现支持这样一种观点，即炎症的作用在 TBI 后的急性和延迟阶段可能不同，并且保持有限的炎症对于修复至关重要。这篇综述探讨了几种细胞因子和趋化因子在局灶性和弥漫性 TBI 后的作用，以及在使用治疗性抗炎治疗与细胞因子表达的基因缺失方面的争议。
