The World Health Organization estimates that as many as 500,000 people will experience spinal cord injuries (SCI) every year. Researchers at the Center for Neuroprosthetics and Brain Mind Institute in Switzerland reported that approximately half of human spinal cord injuries lead to paralysis severe enough to keep the person in a wheelchair for the rest of his or her life. An incomplete spinal cord injury is sufficient to cause severe motor impairments. However, in most of these patients, a few nerve fiber bridges remain at the site of injury. Can researchers figure out a way to repair these paths and help the patient regain functional movement after spinal cord injury?
Researchers at the University of Zurich are putting these spared fibers center stage as a means of restoring locomotor ability by increasing the movement control commands that are carried by these remaining intact highways. The lumbar spinal cord has a locomotor central pattern generator (CPG) that produces rhythmic output without sensory or motor feedback from muscle targets. Spinal cords that have been isolated from the body can still produce activity patterns associated with locomotion. However, to initiate movement the organism needs input from the brain command center.
Previous research in spinal cord injury has focused on promoting the growth of interrupted fibers to reconnect the supraspinal (above the spinal cord) motor cortex to neurons below the site of injury. This type of recovery relies on inducing new circuit formation in individuals who have been newly injured and have retained plasticity. It is more challenging to restore locomotion in individuals, who have been living with their injury for years.
In a new study published in Science Translational Medicine, researchers set out to reactivate the inactive networks below a spinal cord injury in rats with chronic, severe, and incomplete SCI. Despite the requirement of the brain for modulating movement in response to the environment, basic locomotion can be initiated by the midbrain, the brainstem, and the spinal cord. These results suggest that activity in the regions comprising “evolutionarily ancient” areas can give rise to movement independent of the frontal cortex! Deep brain stimulation in the mesencephalic locomotor region (MLR) of rats with severe spinal cord injury immediately improved locomotor performance in the previously paralytic hindlimbs.
This research may have broader implications for other degenerative disorders. Individuals with midbrain ataxia show a deficit in the initiation of walking and have damage in their MLR regions. Parkinson’s patients have severe gait disturbances and reduced activity in the supraspinal motor circuits; they also demonstrate severe neuron loss in the MLR motor region. What do these disorders have in common with spinal cord injury? All three scenarios describe conditions where there is a reduction in the brain-controlled motor command signals that reach the spinal cord. The results of this study suggest that excitatory stimulation in the MLR by deep brain stimulation could be key to improving gait disturbances in Parkinson’s patients! Unraveling the overlap between motor impairments in neurodegeneration and spinal cord injury may lead to a new therapeutic approach for restoring function in both conditions.
To explore further advances in spinal cord injury recovery, we recommend you watch this TED talk, originally recorded in June 2013 at TedGlobal2013, entitled “The Paralyzed Rat That Walked” with Gregoire Courtine.
Bachmann L.C., Matis A., Lindau N.T., Felder P., Gullo M. & Schwab M.E. (2013). Deep Brain Stimulation of the Midbrain Locomotor Region Improves Paretic Hindlimb Function After Spinal Cord Injury in Rats, Science Translational Medicine, 5 (208) 208ra146-208ra146. DOI:10.1126/scitranslmed.3005972
Courtine, C. (2013, June). The Paralyzed Rat That Walked [Video file]. Retrieved from http://www.ted.com/talks/gregoire_courtine_the_paralyzed_rat_that_walked.html
van den Brand R., Heutschi J., Barraud Q., DiGiovanna J., Bartholdi K., Huerlimann M., Friedli L., Vollenweider I., Moraud E.M., Duis S. & Dominici N. (2012). Restoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury, Science, 336 (6085) 1182-1185. DOI: 10.1126/science.1217416
Images adapted from SEBASTIAN KAULITZKI/Science Photo Library/Corbis and from
Goulding M. (2009). Circuits controlling vertebrate locomotion: moving in a new direction, Nature Reviews Neuroscience, 10 (7) 507-518. DOI: 10.1038/nrn2608