Labroo Pratima, Shea Jill, Sant Himanshu, Gale Bruce, Agarwal Jayant
Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA.
Department of Surgery, University of Utah, 30 N 1900 E, 3b400, Salt Lake City, Utah, 84132, USA.
Muscle Nerve. 2017 Apr;55(4):570-581. doi: 10.1002/mus.25370. Epub 2016 Dec 28.
There is a clinical need to improve the outcomes of peripheral nerve regeneration and repair after injury. In addition to its immunosuppressive effects, FK506 (tacrolimus) has been shown to have neuroregenerative properties. To determine biologically relevant local FK506 and growth factor concentrations, we performed an in vitro bioassay using dorsal root ganglion (DRG) from chicken embryos.
Neurite elongation and neurite branching were analyzed microscopically after addition of FK506, glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF), each alone and in combination.
FK506 induced modest neurite elongation (∼500-800 µm) without improving neurite branching significantly. The combination of FK506 with NGF, GDNF, or both, exerted a potentiating or competitive effect on neurite elongation (∼700-1100 µm) based on dosage and competitive effect on neurite branching (∼0.2-0.4).
These results strongly suggest that the interaction of FK506 with GDNF and NGF mediates distinct enhancement of neurite growth. Muscle Nerve 55: 570-581, 2017.
临床上需要改善周围神经损伤后的再生和修复效果。除了具有免疫抑制作用外,FK506(他克莫司)还被证明具有神经再生特性。为了确定生物学相关的局部FK506和生长因子浓度,我们使用鸡胚背根神经节(DRG)进行了体外生物测定。
分别单独及联合添加FK506、胶质细胞源性神经营养因子(GDNF)和神经生长因子(NGF)后,通过显微镜分析神经突伸长和神经突分支情况。
FK506诱导适度的神经突伸长(约500 - 800μm),但未显著改善神经突分支。基于剂量,FK506与NGF、GDNF或两者联合使用,对神经突伸长产生增强或竞争作用(约700 - 1100μm),对神经突分支产生竞争作用(约0.2 - 0.4)。
这些结果强烈表明,FK506与GDNF和NGF的相互作用介导了神经突生长的不同增强作用。《肌肉与神经》55: 570 - 581, 2017年。