Bamber N I, Li H, Lu X, Oudega M, Aebischer P, Xu X M
Department of Anatomy and Neurobiology, St Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA.
Eur J Neurosci. 2001 Jan;13(2):257-68.
To promote axonal regeneration in the injured adult spinal cord, a two-phase repair strategy was employed to (i) bridge a spinal cord hemilesion cavity with a grafted Schwann cell (SC)-seeded mini-channel, and (ii) promote axonal re-entry into the distal cord by infusing two neurotrophins, BDNF and/or NT-3, directly into the distal cord parenchyma. Here we report that infusion of two neurotrophins, delivered alone or in combination, effectively promotes axonal outgrowth from SC-seeded mini-channels into the distal host spinal cord. When an anterogradely transported marker, PHA-L or BDA, was injected into the spinal cord 3 mm rostral to the graft, a large number of axons was observed to regenerate from the SC graft into the distal cord in neurotrophin-treated groups. A subpopulation of these axons was found to grow up to 6 mm within the distal spinal cord. These axons, which were confined mainly within the grey matter, arborized and formed structures which resemble terminal boutons. In channels containing no SCs, the infusion of neurotrophins did not promote axonal ingrowth from the proximal cord stump. In cases which received SC grafts but no neurotrophin infusion, axonal re-entry into the distal cord was limited. Thus, the present study demonstrates that regenerating axons not only cross a lesion site when a permissive cellular bridge is provided but also penetrate into the distal host spinal cord and elongate for a distance of several cord segments after the infusion of two neurotrophins. The latter event is prerequisite for establishment of appropriate connections between regenerating axons and target neurons and thus, functional recovery.
为促进成年受损脊髓的轴突再生，采用了一种两阶段修复策略：（i）用接种雪旺细胞（SC）的微型通道桥接脊髓半切损伤腔；（ii）通过将两种神经营养因子BDNF和/或NT-3直接注入远端脊髓实质来促进轴突重新进入远端脊髓。在此我们报告，单独或联合递送两种神经营养因子，可有效促进接种SC的微型通道中的轴突向远端宿主脊髓生长。当将顺行运输标记物PHA-L或BDA注入移植部位头侧3 mm处的脊髓时，在神经营养因子处理组中观察到大量轴突从SC移植物向远端脊髓再生。发现这些轴突中的一个亚群在远端脊髓内生长长达6 mm。这些主要局限于灰质内的轴突形成分支并形成类似于终末扣的结构。在不含SCs的通道中，神经营养因子的注入并未促进近端脊髓残端的轴突向内生长。在接受SC移植但未注入神经营养因子的情况下，轴突重新进入远端脊髓受到限制。因此，本研究表明，当提供允许性细胞桥时，再生轴突不仅能穿过损伤部位，而且在注入两种神经营养因子后还能穿透进入远端宿主脊髓并延伸几个脊髓节段的距离。后一事件是再生轴突与靶神经元建立适当连接从而实现功能恢复的先决条件。
