Cytological analysis of and strategy for retarded nerve regeneration in aging animals

虽然神经挤压后有髓纤维的再生在衰老动物中被证明是迟缓的，但这种迟缓的因素仍有待确定。为了验证衰老过程中的雪旺细胞功能障碍至少在一定程度上导致反应迟缓的假设，我们研究了2月龄和24-29月龄小鼠坐骨神经横断后雪旺细胞的增殖反应。通过胸苷结合培养24小时的方法评估（Komiyama和Suzuki， 1992a, 1994），青年人神经的雪旺细胞在横切后第1天迅速增殖，并在第3天达到峰值。老年小鼠的雪旺细胞分裂率维持在青年小鼠雪旺细胞的十分之一左右。衰老神经远端残端募集的巨噬细胞数量也少于年轻神经。将衰老小鼠坐骨神经雪旺细胞置于添加15% FBS的培养基中，培养8 d后，其增殖率达到年轻成年小鼠的一半。我们的研究结果表明，雪旺细胞在衰老小鼠损伤神经中的增殖能力受到损害，部分原因是其增殖能力有限。这种雪旺细胞在体内和体外增殖能力的差异可能与衰老小鼠损伤神经内膜间隙巨噬细胞迁移的缺乏有关。

Although regeneration of myelinated fibers after nerve-crush was shown to be retarded in aging animals, the factors of this retardation remains to be determined. To test the hypothesis that Schwann cell dysfunction with aging process was at least in part responsible for the retarded response, we investigated proliferative responses of Schwann cells in the mouse sciatic nerves after nerve-transection at 2 and 24-29 months of age. As assessed by thymidine incorporation for 24h in culture (Komiyama and Suzuki, 1992a, 1994), Schwann cells from young adult nerves proliferated rapidly within day 1 post-transection and reached a peak at day 3. However, division rate of Schwann cells from aging mouse remained at the level about one tenth of Schwann cells from young adult mouse. The number of macrophages recruited in the distal stump was also smaller in the aging nerves than in the young adult nerves. When Schwann cells from the sciatic nerves of aging mouse were maintained in the media supplemented with 15% FBS,the rate of proliferation reached one half of that of young adult mouse during an 8 day period in culture. The results of our study suggest that Schwann cell proliferation is impaired in the injured nerves of aging mouse partly because of their limited capacity to proliferate. This difference in vivo and in vitro proliferative capacity of Schwann cells may be related to the paucity of macrophage migration in the endoneural space of injured nerves of aging mice.