In vivo imaging of axonal degeneration and regeneration in the injured spinal cord.
The poor response of central axons to transection underlies the bleak prognosis following spinal cord injury. Here, we monitor individual fluorescent axons in the spinal cords of living transgenic mice over several days after spinal injury. We find that within 30 min after trauma, axons die back hundreds of micrometers. This acute form of axonal degeneration is similar in mechanism to the more delayed Wallerian degeneration of the disconnected distal axon, but acute degeneration affects the proximal and distal axon ends equally. In vivo imaging further shows that many axons attempt regeneration within 6-24 h after lesion. This growth response, although robust, seems to fail as a result of the inability of axons to navigate in the proper direction. These results suggest that time-lapse imaging of spinal cord injury may provide a powerful analytical tool for assessing the pathogenesis of spinal cord injury and for evaluating therapies that enhance regeneration.
Kerschensteiner
Martin
M
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Schwab
Martin E
ME
Lichtman
Jeff W
JW
Misgeld
Thomas
T
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002154:Calpain / Q000037:antagonists & inhibitors; D005727:Ganglia, Spinal / Q000473:pathology; D006023:Glycoproteins / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009410:Nerve Degeneration / Q000473:pathology*; D009416:Nerve Regeneration / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology*; D013997:Time Factors
D006023:Glycoproteins; C039304:calpain inhibitors; D049452:Green Fluorescent Proteins; D002154:Calpain