Damage to the spinal cord is irreparable. Severe damage leads to serious, permanent impairment of function below the site of the injury. New approaches to treatment are desperately needed to improve the outlook for those affected.
In this project, Professor Di Giovanni has built on an existing body of research from two world-leading labs to test different combinations of rehabilitation and treatment, assessing regeneration and recovery.
It is estimated that there are around 50,000 people living with a spinal cord injury in the UK, with around 1,000 new injuries occurring each year.
Damage to the spinal cord is irreparable. Severe spinal cord injury leads to serious, permanent impairment. Depending on the site of the injury, it may affect not only movement and sensation, but potentially also bowel and bladder function, breathing, heart rate and blood pressure. Rehabilitation has some benefit after moderate spinal cord injury, but fails to improve recovery after more severe injuries.
In contrast to the irreparable nature of damage to the spinal cord (which, together with the brain, forms the central nervous system, CNS), nerves in the peripheral nervous system do have the capacity to grow back.
The peripheral nervous system is the network of nerves that links the CNS to the rest of the body. People with nerve damage in their peripheral nervous system can recover some lost function; about 30 per cent of the nerves grow back and there is often recovery of movement and function.
A key aim is to understand why nerve fibres (axons) in the peripheral nervous system regenerate whilst those in the CNS do not.
Read more: Brain and spinal cord injury
The aim of this project was to understand why axons in the peripheral nervous system regenerate whilst those in the spinal cord do not.
In collaboration with Professor Gregoire Courtine, a world-leader in neuro-rehabilitation from the Swiss Federal Institute of Technology, Professor Giovanni used electrical stimulation in combination with rehabilitation in rodents with spinal cord injury. These techniques were then combined with a drug (TTK21) that had been previously shown to promote axonal regeneration.
When administered in the acute phase, starting 4 to 6 hours after injury, the team showed that TTK21 stimulated neuronal plasticity, regrowth and sprouting, as well as recovery of motor and sensory function in rodents, even after a severe spinal cord injury. Contrary to expectations, however, the combination of electrical stimulation and neurorehabilitation with TTK21 did not show an increase in functional recovery, compared with TTK21 alone.
The team also used the drug in a chronic, severe model of spinal cord injury, starting 12 weeks after injury. This simulates the condition of millions of patients with severe disability following spinal cord injury. Surprisingly, TTK21 was found to promote axonal regeneration in this more extreme injury condition, but did not enhance functional recovery.
There is currently no treatment that can repair a spinal cord injury. Those affected live in hope of a breakthrough that may help them regain lost function.
This work has enhanced understanding of how the effects of TTK21 can promote neuronal plasticity, sprouting and regeneration in models of moderate to severe spinal cord injury in rodents. This gives an insight to mechanisms of repair, and potential new approaches to stimulate repair and recovery after spinal cord injury.
Acquired brain and spinal cord injury (including stroke) is one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of how to promote repair of the brain and spinal cord following injury.
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Find out about our other research in this area:
