Experimental strategies to promote functional recovery after peripheral nerve injuries
Experimental strategies to promote functional recovery after peripheral nerve injuries
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DOI：
10.1111/j.1085-9489.2003.03029.x
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发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Boyd, JG
中科院分区：
文献类型：
--
作者：
Gordon, T;Sulaiman, O;Boyd, JG
周围神经系统中的雪旺细胞(SCs)支持轴突再生的能力，与中枢神经系统中的少突胶质细胞不同，导致了周围神经再生总是能恢复功能的误解。在这里，我们考虑了在轴突再生(慢性轴突切断)期间，受损神经元保持无靶点的时间延长，以及远端神经残端的干细胞保持慢性去神经支配(慢性去神经)如何逐渐减少再生轴突的运动神经元的数量。我们证明了小剂量脑源性神经营养因子和胶质源性神经营养因子在促进轴突再生方面的有效性。另一方面，大剂量脑源性神经营养因子(BDNF)通过p75受体作用，抑制轴突再生，可能是阻止再生轴突在骨骼肌形成神经肌肉连接的一个因素。免疫亲和素FK506在促进慢性轴突切断后轴突再生方面也是有效的。SCs的慢性失神经(>；1个月)严重阻碍轴突的再生，尽管为数不多的再生肌肉的运动轴突会变成有髓鞘，并在再生的肌肉中形成扩大的运动单位。我们发现，在体外培养的慢性失神经干细胞与转化生长因子-P一起在体内重建了其支持生长的表型，这与沃勒变性过程中侵袭的巨噬细胞与失神经的干细胞之间的相互作用对于通过促进支持生长的干细胞表型而维持轴突再生至关重要。最后，我们考虑了短暂的20赫兹电刺激在促进神经修复后穿过手术间隙的轴突再生方面的有效性。
The capacity of Schwann cells (SCs) in the peripheral nervous system to support axonal regeneration, in contrast to the oligodendrocytes in the central nervous system, has led to the misconception that peripheral nerve regeneration always restores function. Here, we consider how prolonged periods of time that injured neurons remain without targets during axonal regeneration (chronic axotomy) and that SCs in the distal nerve stumps remain chronically denervated (chronic denervation) progressively reduce the number of motoneurons that regenerate their axons. We demonstrate the effectiveness of low-dose, brain-derived neurotrophic and glial-derived neurotrophic factors to counteract the effects of chronic axotomy in promoting axonal regeneration. High-dose brain-derived neurotrophic factor (BDNF) on the other hand, acting through the p75 receptor, inhibits axonal regeneration and may be a factor in stopping regenerating axons from forming neuromuscular connections in skeletal muscle. The immunophilin, FK506, is also effective in promoting axonal regeneration after chronic axotomy. Chronic denervation of SCs (>1 month) severely deters axonal regeneration, although the few motor axons that do regenerate to reinnervate muscles become myelinated and form enlarged motor units in the reinnervated muscles. We found that in vitro incubation of chronically denervated SCs with transforming growth factor-P re-established their growth-supportive phenotype in vivo, consistent with the idea that the interaction between invading macrophages and denervated SCs during Wallerian degeneration is essential to sustain axonal regeneration by promoting the growth-supportive SC phenotype. Finally, we consider the effectiveness of a brief period of 20 Hz electrical stimulation in promoting the regeneration of axons across the surgical gap after nerve repair.