Can paraplegics and tetraplegics walk again? The therapeutic potential of neural relay, synaptic organizers and subdural electrical stimulation for spinal cord injury

Spinal cord injury is a debilitating condition in which cell bodies and axons are damaged after accidents or recreational sports, resulting in devastating functional impairment. A major component of spinal cord injury is permanent damage to both ascending (sensory) and descending (motor) axons, which do not properly regenerate without therapeutic interventions. For more than a century, scientists have unsuccessfully tried to find effective ways to regenerate central nervous system axons, since the pioneering work by Albert Aguayo, who induced regeneration of optic nerve axons via a bridge of the sciatic nerve in rodents in the 1980s. In a series of seminal papers, scientists from different laboratories were able to induce conspicuous axonal regeneration and functional recovery in the spinal cord of both experimental animals and humans. In this paper, we review the main findings for three promising regenerative approaches for spinal cord injury: the formation of a new circuit using a neural relay, the use of artificial synaptic organizers and epidural electrical stimulation. We discuss both experimental animal and human data. We conclude that these regenerative approaches give a real hope that a therapy for spinal cord paralysis will be available in some years so that paraplegic and quadriplegic patients will be able to regain sensory function and walk again in the near future. This is already a partial reality for some paraplegic and tetraplegic patients treated with epidural electrical stimulation.