Paralyzed rats walk upon brain stimulation

This year’s ZNZ Best PhD Award went to Lukas Bachmann for the excellent work performed in the group of Martin Schwab at the Brain Research Institute. He and his colleagues could restore mobility in partially paralyzed rats by using a technique called deep brain stimulation. Clinical trials are currently planned to see whether brain stimulation could be a way to treat patients with severe, incomplete spinal cord injury.

BLukasBachmann_150x150achmann’s research involved delivering electrical stimulation to an important control center for locomotion in the brain. Bachmann explains: “In our initial work on the role of the brainstem in the recovery after incomplete spinal cord injury, which I performed in close collaboration with Dr. Björn Zörner, we found that a part of the most ancient motor control system, the gigantocellular reticular nucleus, was crucial for the spontaneous recovery of function after severe damage to the spinal cord. Inspired by these initial findings, Alina Matis, a Master student in our lab at the time, and I set out to address the question if we could improve motor function after severe spinal cord injury by boosting function of the brainstem motor systems. In the course of these experiments we found that if we stimulated the so called mesencephalic locomotor region (MLR) in rats suffering from severe paralysis of the hind limbs caused by spinal cord injury, we could significantly improve walking in these animals.”

Clinical implications
Deep brain stimulation targeting the basal ganglia or the thalamus is currently being used safely and effectively to treat thousands of patients for movement disorders such as Parkinson’s Disease, but has not been used so far after spinal cord injury. Similar to the rats in Bachmann’s paper, in most spinal cord injuries in humans some nerve fibers remain intact, including some of those descending from the MLR and still connect the brain to the spinal cord below the level of injury.
“Our findings in rats, together with the fact that the stimulation can, in principle, be done in humans, makes us cautiously optimistic that we may be on the right course. However, there is still a series of questions that need to be addressed before we can move forward”, says Bachmann. He explains that the MLR is a relatively complex structure and the exact region that has to be stimulated has to be identified. Furthermore, the fact that humans walk on two legs, and therefore balance control is very important for functional walking, has to be considered. Also the nature of the injury, e.g. how much of the spinal cord and function of the lower body has been spared will be crucial for successful treatment. “We now work in close collaboration with our colleagues in neurosurgery at the University Hospital Zurich and the Spinal Cord Injury Center at Balgrist Hospital to figure out practical solutions to these challenges. There is still some way to go, but we are hopeful that we can move forward and test the effectiveness of this deep brain stimulation approach in a first set of patients in the not too distant future”, Lukas Bachmann concludes.

Lukas Bachmann received the ZNZ PhD Award for this outstanding research. In his absence – Bachmann now works at the Salk Institute for Biological Studies in San Diego – his supervisor Martin Schwab presented the work at the 2014 ZNZ Symposium.

Deep brain stimulation of the midbrain locomotor region improves paretic hindlimb function after spinal cord injury in rats. Bachmann LC, Matis A, Lindau NT, Felder P, Gullo M, Schwab ME. Sci Transl Med. 2013 Oct 23;5(208):208ra146 PubMed Abstract

Chasing central nervous system plasticity: the brainstem’s contribution to locomotor recovery in rats with spinal cord injury. Zörner B, Bachmann LC, Filli L, Kapitza S, Gullo M, Bolliger M, Starkey ML, Röthlisberger M, Gonzenbach RR, Schwab ME. Brain. 2014 Jun;137(Pt 6):1716-32 PubMed Abstract