Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation

Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation
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DOI:
10.1016/s0896-6273(02)00702-x
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发表时间:
2002-06-13
期刊:
影响因子:
16.2
通讯作者:
Basbaum, AI
Basbaum, AI
中科院分区:
医学1区
文献类型:
--
作者:
Neumann, S;Bradke, F;Basbaum, AI

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初级感觉神经元的外周分支在损伤后再生,但其中央分支被脊髓损伤切断时没有再生。在这里,我们表明,在腰椎背根神经节中微量注射cAMP的膜渗透性类似物显着增加损伤的中央感觉分支的再生。受损的轴突再生到脊髓损伤中,通常穿过损伤部位。该结果模拟了条件性周围神经损伤的效果。我们还表明,感觉神经元暴露于cAMP在体内,随后在体外培养时,显示出增强的神经突起的生长和克服抑制CNS髓鞘的能力。因此,刺激cAMP信号传导增加了受损感觉轴突的内在生长能力。这种方法可能有助于促进脊髓损伤后的再生。
The peripheral branch of primary sensory neurons regenerates after injury, but there is no regeneration when their central branch is severed by spinal cord injury. Here we show that microinjection of a membrane-permeable analog of cAMP in lumbar dorsal root ganglia markedly increases the regeneration of injured central sensory branches. The injured axons regrow into the spinal cord lesion, often traversing the injury site. This result mimics the effect of a conditioning peripheral nerve lesion. We also demonstrate that sensory neurons exposed to cAMP in vivo, when subsequently cultured in vitro, show enhanced growth of neurites and an ability to overcome inhibition by CNS myelin. Thus, stimulating cAMP signaling increases the intrinsic growth capacity of injured sensory axons. This approach may be useful in promoting regeneration after spinal cord injury.