Institute of Neuronal Cell Biology, Technische Universität München, Munich 80802, Germany.
1] Institute of Neuronal Cell Biology, Technische Universität München, Munich 80802, Germany [2] Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich 81377, Germany.
Nat Commun. 2014 Dec 16;5:5683. doi: 10.1038/ncomms6683.
Therapeutic strategies for spinal cord injury (SCI) commonly focus on regenerating disconnected axons. An alternative approach would be to maintain continuity of damaged axons, especially after contusion. The viability of such neuropreservative strategies depends on the degree to which initially injured axons can recover. Here we use morphological and molecular in vivo imaging after contusion SCI in mice to show that injured axons persist in a metastable state for hours. Intra-axonal calcium dynamics influence fate, but the outcome is not invariably destructive in that many axons with calcium elevations recover homeostasis without intervention. Calcium enters axons primarily through mechanopores. Spontaneous pore resealing allows calcium levels to normalize and axons to survive long term. Axon loss can be halted by blocking calcium influx or calpain, even with delayed initiation. Our data identify an inherent self-preservation process in contused axons and a window of opportunity for rescuing connectivity after nontransecting SCI.
脊髓损伤 (SCI) 的治疗策略通常侧重于再生已断开的轴突。另一种方法是保持受损轴突的连续性，尤其是在挫伤后。这种神经保护策略的可行性取决于最初受损的轴突在多大程度上能够恢复。在这里，我们使用小鼠挫伤性 SCI 后的形态学和分子体内成像来显示损伤的轴突在数小时内仍保持在亚稳态。细胞内钙动力学影响命运，但结果并非总是破坏性的，因为许多钙升高的轴突在没有干预的情况下恢复了内稳态。钙主要通过机械孔进入轴突。自发的孔再封闭允许钙水平正常化，轴突长期存活。即使延迟开始，通过阻断钙内流或钙蛋白酶也可以阻止轴突丢失。我们的数据确定了挫伤轴突中固有的自我保护过程，并为非横断性 SCI 后恢复连接提供了机会之窗。
