Schwab Jan M, Brechtel Klaus, Mueller Christian-Andreas, Failli Vieri, Kaps Hans-Peter, Tuli Sagun K, Schluesener Hermann J
Institute of Brain Research, Calwer Str. 3, University of Tuebingen, Medical School, Calwerstr. 3, 72076 Tuebingen, Germany.
Prog Neurobiol. 2006 Feb;78(2):91-116. doi: 10.1016/j.pneurobio.2005.12.004. Epub 2006 Feb 17.
Detailed pathophysiological findings of secondary damage phenomena after spinal cord injury (SCI) as well as the identification of inhibitory and neurotrophic proteins have yielded a plethora of experimental therapeutic approaches. Main targets are (i) to minimize secondary damage progression (neuroprotection), (ii) to foster axon conduction (neurorestoration) and (iii) to supply a permissive environment to promote axonal sprouting (neuroregenerative therapies). Pre-clinical studies have raised hope in functional recovery through the antagonism of growth inhibitors, application of growth factors, cell transplantation, and vaccination strategies. To date, even though based on successful pre-clinical animal studies, results of clinical trials are characterized by dampened effects attributable to difficulties in the study design (patient heterogeneity) and species differences. A combination of complementary therapeutic strategies might be considered pre-requisite for future synergistic approaches. Here, we line out pre-clinical interventions resulting in improved functional neurological outcome after spinal cord injury and track them on their intended way to bedside.
脊髓损伤(SCI)后继发性损伤现象的详细病理生理学研究结果以及抑制性和神经营养蛋白的鉴定,催生了大量实验性治疗方法。主要目标包括:(i)尽量减少继发性损伤进展(神经保护),(ii)促进轴突传导(神经修复),以及(iii)提供有利于轴突发芽的环境(神经再生疗法)。临床前研究通过拮抗生长抑制剂、应用生长因子、细胞移植和疫苗接种策略,为功能恢复带来了希望。迄今为止,尽管基于成功的临床前动物研究,但临床试验结果的效果却因研究设计困难(患者异质性)和物种差异而受到抑制。互补治疗策略的组合可能被认为是未来协同方法的先决条件。在此,我们列出了能改善脊髓损伤后神经功能结局的临床前干预措施,并追踪它们通向临床应用的预期路径。