A recoverable state of axon injury persists for hours after spinal cord contusion in vivo

Philip R. Williams, Bogdan-Nicolae Marincu, Catherine D. Sorbara, Christoph F. Mahler, Adrian-Minh Schumacher, Oliver Griesbeck, Martin Kerschensteiner () and Thomas Misgeld ()
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Philip R. Williams: Institute of Neuronal Cell Biology, Technische Universität München
Bogdan-Nicolae Marincu: Institute of Neuronal Cell Biology, Technische Universität München
Catherine D. Sorbara: Institute of Neuronal Cell Biology, Technische Universität München
Christoph F. Mahler: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München
Adrian-Minh Schumacher: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München
Oliver Griesbeck: Max-Planck Institute of Neurobiology
Martin Kerschensteiner: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München
Thomas Misgeld: Institute of Neuronal Cell Biology, Technische Universität München

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6683

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