cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury
cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury
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DOI：
10.1038/nm1056
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发表时间：
2004-06-01
期刊：
影响因子：
82.9
通讯作者：
Bunge, MB
中科院分区：
文献类型：
--
作者：
Pearse, DD;Pereira, FC;Bunge, MB
中枢神经元再生轴突，如果提供一个允许的环境;脊髓损伤后，然而，抑制分子的存在，使当地的环境不允许。一个有前途的新策略，诱导神经元克服抑制信号是激活cAMP信号。在这里，我们表明，cAMP水平下降，在吻侧脊髓，感觉运动皮层和脑干脊髓挫伤后。磷酸二酯酶IV抑制剂咯利普兰对cAMP水解的抑制可防止这种减少，并且当与许旺细胞移植物结合时，可促进脊髓上和本体感受轴突的保留和髓鞘形成。此外，结合咯利普兰与注射db-cAMP附近的移植物不仅防止cAMP水平的下降，但增加他们以上的未受伤的控制。这进一步增强轴突保留和髓鞘形成，促进轴突能纤维生长进入和超出移植物，并显著改善运动。这些发现表明，cAMP水平是体内受损CNS轴突的保护、生长和髓鞘形成以及功能恢复的关键。
Central neurons regenerate axons if a permissive environment is provided; after spinal cord injury, however, inhibitory molecules are present that make the local environment nonpermissive. A promising new strategy for inducing neurons to overcome inhibitory signals is to activate cAMP signaling. Here we show that cAMP levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV inhibitor rolipram prevents this decrease and when combined with Schwann cell grafts promotes significant supraspinal and proprioceptive axon sparing and myelination. Furthermore, combining rolipram with an injection of db-cAMP near the graft not only prevents the drop in cAMP levels but increases them above those in uninjured controls. This further enhances axonal sparing and myelination, promotes growth of serotonergic fibers into and beyond grafts, and significantly improves locomotion. These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function.