Li Y, Field P M, Raisman G
The Norman and Sadie Lee Research Centre, Division of Neurobiology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom.
J Neurosci. 1998 Dec 15;18(24):10514-24. doi: 10.1523/JNEUROSCI.18-24-10514.1998.
Precisely localized focal stereotaxic electrolytic lesions were made in the corticospinal tract at the level of the first to second cervical segments in the adult rat. This consistently destroyed all central nervous tissue elements (axons, astrocytes, oligodendrocytes, microglia, and microvessels) in a highly circumscribed area. In a group of these rats immediately after lesioning, a suspension of cultured adult olfactory ensheathing cells was transplanted into the lesion site. Within the first week after transplantation, the cut corticospinal axons (identified by anterograde transport of biotin dextran) extended caudally along the axis of the corticospinal tract as single, fine, minimally branched sprouts that ended in a simple tip, often preceded by a small varicosity. By 3 weeks, the regenerating axons, ensheathed by P0-positive peripheral myelin had accumulated into parallel bundles, which now extended across the full length of the lesioned area and reentered the caudal part of the host corticospinal tract. The transplants contained two main types of cells: (1) p75-expressing S cells, which later formed typical peripheral one-to-one myelin sheaths around individual ensheathed axons, and (2) fibronectin-expressing A cells, which aggregated into tubular sheaths enclosing bundles of myelinated axons. The point of reentry of the axons into the central nervous territory of the caudal host corticospinal tract was marked by the resumption of oligodendrocytic myelination. Thus the effect of the transplant was to form a "patch" of peripheral-type tissue across which the cut central axons regenerated and then continued to grow along their original central pathway.
在成年大鼠的第一至第二颈段水平,对皮质脊髓束进行精确局部定位的立体定向电解损伤。这在高度限定的区域内持续破坏了所有中枢神经组织成分(轴突、星形胶质细胞、少突胶质细胞、小胶质细胞和微血管)。在一组这样的大鼠损伤后立即将培养的成年嗅鞘细胞悬液移植到损伤部位。在移植后的第一周内,切断的皮质脊髓轴突(通过生物素葡聚糖的顺行运输鉴定)作为单一、纤细、分支极少的芽沿着皮质脊髓束的轴线向尾端延伸,末端为简单的尖端,通常前面有一个小的曲张。到3周时,由P0阳性外周髓鞘包裹的再生轴突已聚集成平行束,现在延伸穿过损伤区域的全长并重新进入宿主皮质脊髓束的尾端部分。移植组织包含两种主要类型的细胞:(1)表达p75的S细胞,其后来在单个被包裹的轴突周围形成典型的外周一对一髓鞘;(2)表达纤连蛋白的A细胞,其聚集形成管状鞘,包围有髓鞘轴突束。轴突重新进入尾端宿主皮质脊髓束中枢神经区域的点以少突胶质细胞髓鞘形成的恢复为标志。因此,移植的作用是形成一个外周型组织的“补丁”,切断的中枢轴突通过该“补丁”再生,然后继续沿其原来的中枢路径生长。