Better awareness and improved treatment have both contributed to a reduction in the number of people dying from stroke, leading to an increase in the number of stroke survivors. Unfortunately, however, many survivors are left with life-limiting disabilities.
Dr Barry McColl is working towards the development of a new treatment that could boost brain repair in stroke survivors and improve recovery. He is building on pilot data showing that administration of a protein that acts on certain types of immune cells enhances short-term recovery of forelimb function in mice. He will now assess the effects of this protein in the longer term, and fully understand how it works.
Following rigorous assessment as part of our competitive grant round, this project was recommended for funding for its strong potential to bring new understanding on how manipulation of immune cells could enhance repair of the nervous system following injury. It has high translational potential, with relevance to other areas including traumatic brain injury and dementia.
A stroke is caused by sudden interruption of the blood supply to the brain. This starves the brain tissue of oxygen and glucose, causing brain cells to die. Rapid emergency treatment can limit the damage, saving lives and reducing the long-term harm.
But around half of the 1.3 million stroke survivors in the UK are left with life-limiting disabilities. The nature and severity of the disability will vary depending on the extent of the damage and the exact area of the brain affected, but may include limb weakness, impaired mobility, and problems with speech, balance and co-ordination. All of these impact on the survivor's ability to resume a normal, independent life.
In addition to the huge personal impact on the lives of survivors, the impact on society is enormous. The economic burden of stroke in the UK is estimated at £9 billion a year – including health and social care costs, informal care, productivity losses and benefit payments. Two-thirds of working age survivors are unable to return to work.
Improving stroke recovery is therefore a key goal.
We know from previous research that the area of brain tissue around the stroke damage, and connected regions of the brain, can adapt and reorganise to boost recovery or make-up for lost function. This remarkable ability is known as ‘plasticity’. It helps to explain how, with the help of rehabilitation, people can recover functions that were initially lost. Finding a treatment that can enhance plasticity in stroke patients would facilitate a faster, more complete recovery.
This new work by Dr McColl and colleagues builds on the relatively new understanding of the importance of the immune response in brain recovery and repair. Previous research has shown that immune cells called macrophages can facilitate repair by creating the right conditions. The team proposes that further boosting the helpful functions of macrophages could enhance plasticity and improve recovery.
With other colleagues at the University of Edinburgh, they have created a modified version of a naturally-occurring protein that controls various functions of macrophages. In a proof-of-concept study, they have shown that treating mice with this modified protein improved their ability to use their forepaw in the first week after stroke.
Because long-term recovery is what ultimately matters to patients, and to rule out that this is a transient effect, Dr McColl now needs to check whether the treatment can enable better recovery in the longer-term, and to learn more about how it does this and how the effects can be monitored, for example using neuroimaging techniques.
Edinburgh is one of the top research centres in the UK for neuroregenerative research and neuroimaging and has in place all of the key resources for successful delivery of this project.
The project brings together a team of leading basic and clinical researchers, blending their extensive experience and expertise in preclinical and translational stroke studies. Dr Barry McColl is widely recognised as a leader in the field of neuroimmunology, with more than 15 years’ experience investigating neuroimmune mechanisms in stroke, and a number of recent key discoveries in the field. Co-investigator Dr Lawrence Moon, of King’s College London, brings crucial expertise in neuroplasticity after CNS injury. And the team’s expertise is further complemented by the inclusion of Dr Gerry Thompson, an NHS neuroradiologist with clinical and research interests in neuroimaging.
"The participation of scientists expert in each technical part of the project is a guarantee of success” - External reviewer
The effects of stroke are devastating and rob people of their ability to live a productive, independent life. This project is a crucial step in the development of a potential new treatment to boost brain repair in stroke survivors and enhance recovery of function.
The work will give further insight as to how immune cells can be manipulated to influence neuroplasticity and functional recovery after stroke, with applicability to other types of brain injury, as well as neurodegenerative diseases.
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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