Background
In a healthy spinal cord, information from the brain passes down to specialised circuits that control and coordinate functions such as walking. Even though movement is coordinated by these spinal circuits there is a need to have input from the brain to stop, start and make other adjustments.
After SCI, commands from the brain are reduced or lost below the level of the injury and the circuits adapt inappropriately in response. Treadmill training is still one of the most effective ways to improve functional recovery.The mechanisms underlying this strategy remain largely unknown but it is known to produce positive effects on the damaged spinal circuits. Understanding the fundamental processes driving these beneficial changes will be crucial in developing more efficient and effective interventions for people who have been paralysed.
Our University of Leeds team, led by Professor R Edgerton, Professor J Deuchars and Dr Ichiyama, is trying to:
determine what cellular and biochemical changes occur in spinal circuits following spinal cord injury and
compare these to beneficial changes seen when treadmill training is applied.
Report:
We have successfully completed all experimental stages of the proposed studies. We have been successfully applying a small electrical stimulation to the surface of the spinal cord in our injury model to produce stepping. This allows us to train laboratory animals to take steps again, even after a complete SCI. This is a major advancement in our knowledge.
We have generated a large volume of tissue samples and detailed analysis of changes in specific cells in the spinal cord due to the injury and/or treadmill training are presently being carried out.
This will determine whether inhibitory (i.e. cells that prevent activation) nerve cells become active after an injury and whether daily step training can reverse this. Accordingly, we are also investigating whether excitatory nerve cells (i.e. cells that facilitate activation) are deactivated by the injury and ‘reawakened’ by daily treadmill training.
These observations are fundamental to improve the effectiveness of rehabilitative interventions. For example, if our analysis suggests that only the inhibitory neurons are changing with injury and step training, those neurons can become specific targets for pharmacological interventions. It can be envisioned that specific drugs targeted at those cells could be delivered after injury to enhance the recovery of movement and feeling.
