A new breakthrough in the successful rehabilitation of laboratory rats with spinal cord injuries offers long-term hope for similar results with humans.
Scientists in Switzerland, using robot-assisted rehabilitation and electrochemical spinal cord stimulation, have helped rats with clinically relevant spinal cord injuries to regain control of their paralyzed limbs.
The researchers wanted to know how brain commands for functions such as walking or climbing stairs bypass the injury and still reach the spinal cord to execute such complex tasks.
These scientists, at the Ecole Polytechnique Fédérale de Lausanne (Swiss Federal Institute of Technology), or EPFL, say they observed for the first time that the brain reroutes task-specific motor commands through alternative pathways that originate in the brainstem and project to the spinal cord.
The therapeutic treatment triggers the growth of new connections from the motor cortex into the brainstem, and from the brainstem into the spinal cord.
This sequence reconnects the brain with the spinal cord — below the injury.
Grégoire Courtine, PhD, the principal investigator, and Léonie Asboth, a doctoral student at EPFL, published their last month in the journal Nature Neuroscience.
Courtine is an associate professor at EPFL where he holds the International Paraplegic Foundation chair in spinal cord repair at the Center for Neuroprosthetics and the Brain Mind Institute.
“The brain develops new anatomical connections through regions of the nervous system that are still intact after injury,” Courtine said in a news release on the EPFL website. “The brain essentially rewires circuits from the cerebral cortex, brainstem, and spinal cord — an extensive rewiring that we exposed to unprecedented detail using next-generation whole brain-spinal cord microscopy.”
Asboth, the lead author of the EPFL study, said in the same release: “The recovery is not spontaneous. You need to engage the animals in an intense rehabilitation therapy for the rewiring to take place. In our case, this therapy involves electrochemical stimulation of the spinal cord and active physiotherapy in a smart assistive harness.”
Today, after 15 years of research with rats and monkeys, Courtine is directing trials with human patients.
“I am conducting a clinical trial at the University Hospital Lausanne, together with neurosurgeon Dr. Jocelyne Bloch,” he told Healthline. “Several patients have been implanted with the same stimulation technology we used in primates and are now following the rehabilitation program.”
The results will be published later this year or sometime next year, he said.
Long journey on research
Courtine talked about his research in a video that summarizes the presentation he made at the 13th World Congress of the International Neuromodulation Society on May 31, 2017, in Edinburgh, Scotland.
He said he began his research — first with rodents, then nonhuman primates (monkeys), and now human patients — as a postdoctoral fellow at the Brain Research Institute at the University of California, Los Angeles. He then continued the research as a faculty member at the University of Zurich, then at EPFL.
From the beginning, his goal has been to “develop interventions to accelerate and improve the functional recovery from spinal cord injuries.”
Spinal cord injuries (SCI) interrupt communication between the brain and the lumbar spine.
“In rodents, we reactivated the lumbar circuits to provide to the cells the type of information the brain would deliver naturally, in order to walk,” Courtine said in the video. “We use two forms of modulation — pharmacological and electrical stimulation. We call this electrochemical neuroprosthesis, and with it we transform the brain circuit from dormant to a highly functional state.”
On a treadmill, paralyzed rats could show coordinated movements, but they were completely involuntary, Courtine said.
Those movements show the ability of the spinal cord to process information and to activate the muscle in a coordinated manner to produce an automated stepping pattern.
This is the first step of this SCI intervention, he said, and it immediately enables motor control.
Training paralyzed rats to walk again
The rehabilitation involves some training.
“We train the animals, but not in a classical manner,” Courtine said. “We developed a cutting-edge robotic interface that enabled us to support the rats, similar to the way a father would hold up a young child making its first steps. But the rat had to work very hard to engage the paralyzed leg.”
“In the beginning, it did not work very well,” he added. “The animal can walk very well on the treadmill, but when we put it on the robotic interface, we can see that the animal is stuck and cannot engage his paralyzed leg.”
Then, progressively, the animal makes one or two steps. But it’s a difficult process, Courtine said, and the strain can be seen on the animal’s face.
“Yet, he realizes the first steps,” he said. “From this moment, they improve every day. They get better and better. And after several months of rehabilitation, a rat that would normally be completely paralyzed decides to start sprinting to the wall we put in front of the runway.”
That was the first time in experimenting with spinal cord medicine that Courtine and his colleagues had observed the recovery of full-time movement after a lesion led to full-time paralysis of a lower limb.
What’s the physical mechanism that allows this reconnection?
Courtine said what he discovered was unexpected.
“We developed a very extensive tool box of neurotechnology. This has been key to creating an evidence-based concept to apply the stimulation in higher mammals and, eventually, humans. To reflect the intention of the animal, we implanted an electrode into the brain of the nonhuman primates (monkeys) in the region that controls the motor cortex, which normally controls leg movements.”
“We did not aim to regenerate or regrow the severed fibers, yet the highly functional state of the circuit below the injury encouraged the system to grow new fibers,” he said. “These fibers did not go through the injury, but are dependent on spare tissue bridges that establish new connections, and those support the recovery of the brain control that moves the paralyzed leg.”
Research produces new SCI insights
Daofen Chen, PhD, is program director for systems and cognitive neuroscience and neurorehabilitation at the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health.
NINDS is the major funding agency that supports clinical research of neurological diseases, including SCI.
“This is perhaps one of the most comprehensive SCI animal studies conducted in recent years, using an array of cutting-edge research tools and innovative experimental approaches,” Chen told Healthline. “It is indeed groundbreaking in providing new insights in our understanding of the neural structures and functions, and the possible underlying mechanisms, associated with the recovery process after SCI.”
The strength of this study, Chen said, is its strong scientific premise and rigorous experimental designs, with significant efforts to identify and confirm potential causal relationships.
“The study has demonstrated that both neuromodulation such as stimulations, either electrically or pharmacologically, and behavioral interventions such as physical rehab trainings, are essential for the recovery process.”
After his significant breakthrough, and with clinical trials underway with human patients, Courtine is optimistic.
“We previously showed that plasticity — the remarkable ability of the nervous system to grow new connections after spinal cord injury — is even more robust in humans than in rodents,” he said.