McDonald David, Cheng Chu, Chen Yuanyuan, Zochodne Douglas
Department of Clinical Neurosciences, University of Calgary, Canada.
Neuron Glia Biol. 2006 May;2(2):139-47. doi: 10.1017/S1740925X05000347.
Early regeneration of injured peripheral nerves involves a series of events that are important in the success of eventual reconnection. In many nerve injuries, such as transections with gaps, axons and Schwann cells (SCs) penetrate into new microenvironments de novo, not involving zones of Wallerian degeneration. We studied unexplored axon-SC interactions by sampling of newly forming connections through a silicone conduit across transected rat sciatic peripheral nerve gaps. Axon and SC participation in bridge formation was addressed by light microscopy, electron microscopy and by double-labeling immunohistochemistry,including confocal imaging, and several, less appreciated aspects of early regrowth were identified. There are limitations to early and widespread regeneration of axons and SCs into bridges initially formed from connective tissue and blood vessels.Regrowth is 'staggered' such that only a small percentage of parent axons sampled the early bridge. There is an intimate, almost invariable relationship between SCs and extension of axons, which challenges the concept that axons lead and SCs follow.'Naked' axons were infrequent and limited in scope. Axons did not seek out and adhere to vascular laminin but intimately followed laminin deposits associated with apposed SCs. Growth cones identified by labeling of beta III tubulin, PGP(9 x 5) and GAP(43)/B(50) were complex, implying a pause in their regrowth, and were most prominent at the proximal stump-regenerative bridge interface. There is surprising and substantial hostility to local regrowth of axons into newly forming peripheral nerve bridges.Early axon outgrowth, associated with apposed Schwann cell processes, is highly constrained even when not exposed to adjacent myelin and products of Wallerian degeneration.
受损周围神经的早期再生涉及一系列对最终重新连接成功至关重要的事件。在许多神经损伤中，如伴有间隙的横断伤，轴突和施万细胞（SCs）会重新进入新的微环境，而不涉及沃勒变性区域。我们通过对穿过横断大鼠坐骨神经间隙的硅胶导管中新形成连接进行采样，研究了未被探索的轴突 - 施万细胞相互作用。通过光学显微镜、电子显微镜以及双标记免疫组织化学（包括共聚焦成像）来研究轴突和施万细胞在桥形成中的参与情况，并确定了早期再生中几个较少被认识到的方面。轴突和施万细胞向最初由结缔组织和血管形成的桥的早期广泛再生存在局限性。再生是“交错的”，以至于只有一小部分母轴突进入早期桥。施万细胞与轴突延伸之间存在密切且几乎不变的关系，这对轴突领先而施万细胞跟随的概念提出了挑战。“裸露”的轴突很少见且范围有限。轴突不会寻找并黏附于血管层粘连蛋白，而是紧密跟随与相邻施万细胞相关的层粘连蛋白沉积。通过βIII微管蛋白、PGP(9 x 5)和GAP(43)/B(50)标记鉴定的生长锥很复杂，这意味着它们的再生存在停顿，并且在近端残端 - 再生桥界面最为突出。轴突向新形成的周围神经桥的局部再生存在令人惊讶的强烈阻碍。即使不接触相邻的髓磷脂和沃勒变性产物，与相邻施万细胞突起相关的早期轴突生长也受到高度限制。
