Mackay Institute of Research and Innovation, Mackay Hospital and Health Service, Mackay, QLD; and School of Health, Medical, and Applied Sciences, Central Queensland University, Rockhampton, QLD
J Pharmacol Exp Ther. 2022 Aug;382(2):149-166. doi: 10.1124/jpet.121.001023. Epub 2022 May 29.
Traumatic brain injury (TBI) is a major contributor to disability and death worldwide, and manifests in cognitive, behavioral, and motor impairment. Although there have been numerous pre-clinical studies that have identified promising pharmacologic treatments, to date, all Phase III clinical trials have failed. Thus, this is a priority area for ongoing research and development. Treatment strategies have traditionally focused on neuroprotection of the injured brain to reduce secondary injury, neuronal death, and lesion size. The aim of this minireview is to describe the secondary injury pathophysiology of TBI and give an examination of key targets of neuroprotection, select Phase III trials that have been undertaken, and future possibilities for successful drug development. SIGNIFICANCE STATEMENT: This minireview provides an up-to-date summary of the key Phase III clinical trials that have been undertaken in the development of a neuropharmacological treatment for traumatic brain injury. The article discusses the key targets for treatment, the potential reasons for the lack of translation of promising pre-clinical compounds, and the most promising avenues for future development.
创伤性脑损伤（TBI）是全球残疾和死亡的主要原因，表现为认知、行为和运动障碍。尽管有许多临床前研究已经确定了有前途的药物治疗方法，但迄今为止，所有三期临床试验都失败了。因此，这是正在进行的研究和开发的优先领域。治疗策略传统上侧重于保护受伤大脑的神经，以减少继发性损伤、神经元死亡和病变大小。本篇综述的目的是描述 TBI 的继发性损伤病理生理学，并检查神经保护的关键靶点、已进行的选择三期试验，以及未来成功药物开发的可能性。意义声明：本篇综述提供了一个最新的总结，重点介绍了在开发创伤性脑损伤神经药理学治疗方法方面进行的关键三期临床试验。文章讨论了治疗的关键靶点、有前途的临床前化合物未能转化为临床应用的潜在原因，以及未来最有前途的发展途径。
