Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

中文翻译：

---

治疗颅脑损伤的多功能药物。


创伤性脑损伤 (TBI) 仍然是全球 45 岁以下个体死亡和发病的主要原因之一，尽管人们在开发神经保护疗法方面做出了巨大努力，但迄今为止，任何神经保护试验都没有取得成功的结果。除了认识到许多 TBI 临床试验并未经过最佳设计来检测潜在疗效外，失败的主要原因还在于大多数研究的疗法都是针对个体损伤因素。目前对 TBI 的看法是一种非常异质的损伤类型，其病因、临床表现、严重程度和病理生理学差异很大。 TBI 后神经细胞死亡的机制涉及急性和延迟的解剖、分子、生化和生理事件的相互作用，这些事件既复杂又多方面。因此，神经药物疗法需要针对导致继发性损伤级联的多种损伤因素，并在此过程中最大限度地提高成功结果的可能性。本综述重点关注许多此类多功能化合物，这些化合物在实验研究中取得了相当大的成功，并且在临床试验中显示出成功的最大希望。