Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries.
Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries.
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DOI：
10.1016/j.actbio.2018.07.048
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发表时间：
2018-09-15
影响因子：
9.7
通讯作者：
Romero-Ortega MI
中科院分区：
文献类型：
--
作者：
Alsmadi NZ;Bendale GS;Kanneganti A;Shihabeddin T;Nguyen AH;Hor E;Dash S;Johnston B;Granja-Vazquez R;Romero-Ortega MI
超过3 cm的神经间隙损伤的修复受到需要牺牲供体组织和与自体移植金标准相关的发病率的限制，而脱细胞移植物和可生物降解的导管仅在短神经缺损中有效。同基因神经植入物的优点似乎是释放各种生长因子的失神经施万细胞。我们评估了血管内皮生长因子、神经营养因子和多腔导管的多效营养因子（PTN）补充在兔腓神经3和4 cm神经间隙修复中的作用。体外筛选显示PTN与胶质源性神经营养因子（GDNF）在促进感觉轴突密度和脊髓外植体运动轴突生长方面具有协同再生作用。在体内，多效生长因子能够支持神经再生跨越3厘米的差距。在4 cm病变中，PTNGDNF对植入物远端的轴突数量具有适度影响，同时与单独的PTN或GDNF（分别为0.80 ± 0.2，0.84 ± 0.5）相比，增加了平均轴突直径（1 ± 0.4; p ≤ 0.001）。神经肌肉接头染色显示，一些再生的轴突重新支配肌肉靶点。然而，许多被包裹在Remak束中，这表明轴突分类延迟，解释了再神经支配肌肉的有限电生理功能，以及PTN-GDNF修复动物中脚趾伸展的适度恢复。这些结果支持在长间隙修复中使用协同神经营养/多效性生长因子，并强调需要在损伤部位远端进行髓鞘再生策略。
The repair of nerve gap injuries longer than 3 cm is limited by the need of sacrifice donor tissue and morbidity associated with the autograft gold standard, while decellularized grafts and biodegradable conduits are effective only in short nerve defects. The advantage of isogenic nerve implants seems to be the release of various growth factors by the denervated Schwann cells. We evaluated the effect of vascular endothelial growth factor, neurotrophins, and pleiotrophin (PTN) supplementation of multiluminal conduits, in the repair of 3 and 4 cm nerve gaps in the rabbit peroneal nerve. In vitro screening revealed a synergistic regenerative effect of PTN with glial-derived neurotrophic factor (GDNF) in promoting sensory axon density, and in motor axonal growth from spinal cord explants. In vivo, pleiotrophins were able to support nerve regrowth across a 3 cm gap. In the 4 cm lesions, PTNGDNF had a modest effect in the number of axons distal to the implant, while increasing the mean axon diameter (1 ± 0.4; p ≤ 0.001) over PTN or GDNF alone (0.80 ± 0.2, 0.84 ± 0.5; respectively). Some regenerated axons reinnervated muscle targets as indicated by neuromuscular junction staining. However, many were wrapped in Remak bundles, suggesting a delay in axonal sorting, explaining the limited electrophysiological function of the reinnervated muscle, and the modest recovery in toe spreading in the PTN-GDNF repaired animals. These results support the use of synergistic neurotrophic/pleiotrophic growth factors in long gap repair and underscore the need for remyelination strategies distal to the injury site.
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影响因子：
64.5
作者：
Bonanomi D;Chivatakarn O;Bai G;Abdesselem H;Lettieri K;Marquardt T;Pierchala BA;Pfaff SL
通讯作者：
Pfaff SL
DOI：
10.1083/jcb.201205025
发表时间：
2012-07-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fontana X;Hristova M;Da Costa C;Patodia S;Thei L;Makwana M;Spencer-Dene B;Latouche M;Mirsky R;Jessen KR;Klein R;Raivich G;Behrens A
通讯作者：
Behrens A
影响因子：
5.3
作者：
Brushart, TM;Jari, R;Gordon, T
通讯作者：
Gordon, T
影响因子：
3.2
作者：
Blondet, B;Carpentier, G;Courty, J
通讯作者：
Courty, J
影响因子：
4.1
作者：
Gordon, Tessa
通讯作者：
Gordon, Tessa