Spinal cord repair strategies: why do they work?

Although potential therapeutic strategies for spinal cord injury are emerging, the mechanisms underlying functional recovery are unclear. Recent work emphasizes the contribution of axon regeneration and plasticity, yet their involvement, and that of less well-explored processes, remains to be established. 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.