Xiong Ye, Mahmood Asim, Chopp Michael
Henry Ford Health System, Department of Neurosurgery, Detroit, MI 48202, USA.
Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84. doi: 10.1517/14728210902769601.
This review summarizes promising approaches for the treatment of traumatic brain injury (TBI) that are in either preclinical or clinical trials.
The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented.
A literature review of preclinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided.
RESULTS/CONCLUSION: Nearly all Phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials that seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.
本综述总结了处于临床前或临床试验阶段的、有前景的创伤性脑损伤(TBI)治疗方法。
描述TBI后神经功能缺损的病理生理学机制。概述具有神经保护和神经修复作用的TBI精选治疗方法。
提供了与神经保护和神经修复治疗方法相关的临床前TBI研究和临床TBI试验的文献综述。
结果/结论:几乎所有神经保护方面的II/III期临床试验均未显示TBI患者的预后有任何持续改善。未来十年将见证越来越多旨在将临床前研究发现转化为临床应用的临床试验。有前景的基于药物或细胞的治疗方法包括促红细胞生成素及其氨甲酰化形式、他汀类药物、骨髓基质细胞、单独或联合使用的干细胞或与生物材料联合使用,以通过神经保护减少脑损伤,并通过血管生成、神经发生和突触形成促进脑重塑,最终目标是改善TBI患者的功能预后。此外,丰富环境和自主体育锻炼在促进TBI后的功能预后方面显示出前景,应作为TBI的治疗方法单独或与其他治疗联合进行评估。