In vivo imaging of axonal degeneration and regeneration in the injured spinal cord

  title={In vivo imaging of axonal degeneration and regeneration in the injured spinal cord},
  author={Martin Kerschensteiner and Martin E. Schwab and Jeff William Lichtman and Thomas Misgeld},
  journal={Nature Medicine},
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… 
An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.
The ex vivo living spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time.
Live imaging of dorsal root axons after rhizotomy.
Several strategies are described that are found useful to assure successful long-term and repeated imaging of regenerating DR axons, including methods that eliminate repeated intubation and respiratory interruption, minimize surgery-associated stress and scar formation, and acquire stable images at high resolution without phototoxicity.
Another Barrier to Regeneration in the CNS: Activated Macrophages Induce Extensive Retraction of Dystrophic Axons through Direct Physical Interactions
These data are the first to indicate a direct role of activated macrophages in axonal retraction by physical cell–cell interactions with injured axons within the dorsal columns after spinal cord injury in vivo.


The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats
The anatomical basis of this recovery was investigated and it was found that after incomplete spinal cord injury in rats, transected hindlimb corticospinal tract axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (PSNs).
Degeneration and Sprouting of Identified Descending Supraspinal Axons after Contusive Spinal Cord Injury in the Rat
The results of the present study suggest that these two descending systems show a delayed regenerative response and do extend axons into the lesion cavity and that the endogenous repair can continue for a very long time after SCI.
Effects of Neurotoxic and Neuroprotective Agents on Peripheral Nerve Regeneration Assayed by Time-Lapse Imaging In Vivo
It is proposed that neuropathy is the major dose-limiting side effect of vincristine and its efficacy could be enhanced by coadministration of FK506 analogs that are neuroactive but not immunosuppressive, which would have many advantages over currently available behavioral, electrophysiological, and radiometric tests.
Sprouts from Cut Corticospinal Axons Persist in the Presence of Astrocytic Scarring in Long-Term Lesions of the Adult Rat Spinal Cord
Cut corticospinal axons retain extensive terminal and collateral arborizations even in the macrophage-filled central lesion area and are myelinated or ensheathed by endogenous Schwann cells at survivals long enough for the formation of a dense, astrocytic scar.
Chronically Injured Supraspinal Neurons Exhibit Only Modest Axonal Dieback in Response to a Cervical Hemisection Lesion
While some modest changes occur in specific supraspinal pathways following SCI, axonal retraction does not appear to be a contributing factor to the diminished regenerative effort by certain brain stem neurons that has been observed at long postinjury intervals.
Spinal Axon Regeneration Induced by Elevation of Cyclic AMP
Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury
Therapeutic neutralization of CD95L, but not of TNF, significantly decreased apoptotic cell death after SCI and promoted axonal regeneration and functional improvement in injured adult animals.
False resurrections: Distinguishing regenerated from spared axons in the injured central nervous system
The “spared axon conundrum” is illustrated and criteria that may be used to identify regenerated vs. spared axons are proposed, focusing on the injured spinal cord.
Corticospinal Tract Plasticity and Astroglial Reactivity after Cervical Spinal Injury in the Postnatal Rat
Data show that there is an age-related change in the ability of CS axons to grow around spinal injury which ends near the time CS elongation and gliogenesis is complete in the spinal cord.