Chronic nerve compression induces concurrent apoptosis and proliferation of Schwann cells
Chronic nerve compression induces concurrent apoptosis and proliferation of Schwann cells
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DOI：
10.1002/cne.10692
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发表时间：
2003-06-23
影响因子：
2.5
通讯作者：
Steward, O
中科院分区：
文献类型：
--
作者：
Gupta, R;Steward, O
慢性神经压迫（CNC），如腕管综合征，是人类周围神经功能障碍的常见原因。先前使用动物模型的研究已经证明进行性脱髓鞘和神经传导速度减慢。为了表征施瓦姆细胞对 CNC 的反应，我们评估了 CNC 动物模型中的施万细胞总数、细胞凋亡和增殖。基于设计的立体学技术揭示了 CNC 后 Schwarm 细胞数量的显着短暂增加。 1 个月时，受压部位的施瓦姆细胞数量相对于正常神经增加了六倍，然后缓慢下降至对照水平。然而，细胞凋亡分析（TUNEL 和抗聚 ADP 核糖聚合酶标记分析）显示，在压缩后 2 周，即施万细胞数量增加的时期，施万细胞发生了广泛的凋亡。电子显微镜分析证实，施瓦姆细胞中的这些巨大变化是在没有轴突变性和轴突肿胀的情况下以及在神经传导速度出现任何可检测到的变化之前发生的。溴脱氧尿苷标记的雪旺细胞计数显示增殖与正在进行的细胞凋亡同时发生。为了进一步定义机械刺激对施瓦姆细胞可能的有丝分裂特性，我们使用体外模型以层流流体流的形式向纯施万细胞群传递剪切应力，并证实机械刺激诱导施瓦姆细胞增殖。我们的研究结果表明，慢性神经压迫会诱导施瓦姆细胞更新，同时轴突损伤最小，并支持机械刺激对施万细胞有直接有丝分裂作用的观点。
Chronic nerve compression (CNC), as in carpal tunnel syndrome, is a common cause of peripheral nerve dysfunction in humans. Previous studies using animal models have demonstrated progressive demyelination and a slowing of nerve conduction velocity. To characterize the Schwarm cell response to CNC, we evaluated total Schwann cell number, apoptosis, and proliferation in an animal model of CNC. Design-based stereologic techniques revealed a striking transient increase in Schwarm cell number following CNC. Schwarm cell number increased sixfold relative to the normal nerve at the site of compression at 1 month and then slowly declined toward control levels. Nevertheless, assays of apoptosis (TUNEL and an antipoly-ADP-ribose polymerase labeling assays) revealed extensive Schwann cell apoptosis at 2 weeks postcompression, which is during the time when Schwann cell number was increasing. Electron microscopic analysis confirmed that these dramatic changes in Schwarm cells occurred in the absence of axon degeneration and axonal swelling and before there were any detectable alterations in nerve conduction velocity. Counts of bromodeoxyuridine-labeled Schwann cells revealed that proliferation occurred concurrently with ongoing apoptosis. To define further the possible mitogenic properties of mechanical stimuli on Schwarm cells, we used an in-vitro model to deliver shear stress in the form of laminar fluid flow to pure populations of Schwann cells and confirmed that mechanical stimuli induce Schwarm cell proliferation. Our findings indicate that chronic nerve compression induces Schwarm cell turnover with minimal axonal injury and support the idea that mechanical stimuli have a direct mitogenic effect on Schwann cells.