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

虽然有髓神经纤维再生后，神经压榨显示出延迟在老龄动物，这种延迟的因素仍有待确定。为了验证许旺细胞功能障碍与衰老过程中至少部分负责反应迟缓的假设，我们研究了神经横断后，在2个月和24-29个月的年龄在小鼠坐骨神经中的许旺细胞的增殖反应。通过在培养物中掺入胸苷24小时进行评估（Komiyama和Suzuki，1992 a，1994），来自年轻成人神经的许旺细胞在横断后第1天内迅速增殖，并在第3天达到峰值。而老年小鼠雪旺细胞的分裂率仅为青年小鼠雪旺细胞的十分之一左右。在远端残端招募的巨噬细胞的数量也较小，在老化的神经比年轻的成年神经。从老年小鼠坐骨神经分离的雪旺细胞在添加15%FBS的培养基中培养8天，其增殖率可达青年小鼠的一半。我们的研究结果表明，雪旺细胞增殖受损的损伤神经的老化小鼠的部分原因是因为他们的有限的增殖能力。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的神经内膜间隙中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.