Spinal cord repair strategies: why do they work?


There are now numerous preclinical reports of various experimental treatments promoting some functional recovery after spinal cord injury. Surprisingly, perhaps, the mechanisms that underlie recovery have rarely been definitively established. Here, we critically evaluate the evidence that regeneration of damaged pathways or compensatory collateral sprouting can promote recovery. We also discuss several more speculative mechanisms that might putatively explain or confound some of the reported outcomes of experimental interventions.

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Figure 1: Structure of the spinal cord.
Figure 2: The major functional deficits associated with spinal cord injury arise from the interruption of long ascending and descending spinal tracts.
Figure 3: Restoration of function after spinal cord injury might arise from anatomical plasticity of damaged or spared connections.
Figure 4: Various well-established phenomena might contribute to functional recovery from spinal cord injury after experimental interventions.


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The work of the authors is supported by grants from the Medical Research Council and the Wellcome Trust, whom we would like to thank. We would also like to thank T. Boucher and D. Bennett for advice on the manuscript.

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Correspondence to Stephen B. McMahon.

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Pain from stimuli that are not normally painful.

Chondroitinase ABC

(ChABC). A bacterial enzyme that cleaves the sugar (glycosaminoglycan) chains from proteoglycan molecules, rendering them less inhibitory to growth.

Contact-placing responses

In response to light contact of the foot an animal will lift its limb and place it on a surface for support.

Glial scar

Following CNS injury, activated glial cells form a meshwork of interweaving processes that surround the lesion site. Scarring is important for sealing the wound but can also act as an impenetrable barrier to regeneration.


A monosynaptic reflex elicited by electrically stimulating a nerve with an electric stimulus.

Immediate-early genes

A family of genes that share the characteristic of having their expression rapidly and transiently induced on stimulation.


A protective effect from injury achieved by a previous insult (thought to be mediated by pro-regenerative changes in the cell body triggered by the insult).


Transection of the corticospinal tract (CST) at the level of the medullary pyramids in the brainstem. A unilateral pyramidotomy lesions the CST on one side, leaving the other side intact (thereby denervating one side of the spinal cord).


An injury to the spinal dorsal roots that results in an interruption of sensory input from the PNS into the spinal cord.

Transcranial magnetic stimulation

Involves creating a strong localized transient magnetic field that induces current flow in underlying neural tissue, causing a temporary change in activity in small regions of the brain.

Wallerian degeneration

Degeneration that occurs after axonal injury in the distal segment of a nerve fibre – the part no longer connected to the cell body.

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Bradbury, E., McMahon, S. Spinal cord repair strategies: why do they work?. Nat Rev Neurosci 7, 644–653 (2006). https://doi.org/10.1038/nrn1964

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