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Stroke: Using immune cells to boost brain repair

Project details

Researcher
Dr Barry McColl
Institute
University of Edinburgh
Research area
Stroke
Funding type
Project grant
Awarded in
September 2019
Completion
Ongoing

Overview

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 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, and he will now assess the effects of the 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.

About stroke

Stroke happens when blood supply to the brain is suddenly interrupted. This starves the brain of oxygen and glucose, causing brain cells to die. The consequences can be devastating.

Thankfully the number of deaths from stroke is going down, and is now less than half what it was 30 years ago. This is partly due to a reduction in the incidence of strokes but is also a reflection of the greater awareness of symptoms, and better emergency treatments.

The lower mortality rates mean that more people are surviving stroke than ever before, and it is estimated that there are 1.2 million stroke survivors in the UK today.

But over half of stroke survivors are left with a life-limiting disability. Stroke-related disabilities vary depending on the extent of the damage and the exact area of the brain affected, but include limb weakness, impaired mobility, and problems with speech, balance and co-ordination.

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.

Read more: Stroke

Using immune cells to aid repair of the brain after stroke

Existing treatments for ischaemic stroke work by unblocking the damaged artery; this needs to be done very quickly after stroke happens in order to limit the damage. There is no treatment currently approved to treat stroke patients beyond this initial emergency treatment – to help the damaged brain heal.

We know from previous research that the area of brain tissue around the stroke damage, and connected regions, can adapt and reorganise to boost recovery or make-up for lost function. This remarkable ability of the brain to ‘rewire’ itself 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 other cell types, including some types of immune cells called macrophages, can help the nerve cells by creating the right conditions for repair to take place.  

The team proposes that further boosting the helpful functions of macrophages, including specialised macrophages called microglia that live in the brain, could enhance plasticity and improve recovery.

With colleagues at the University of Edinburgh, they recently made a modified version of a protein that occurs naturally in the body and controls various functions of macrophages. In a proof-of-concept study, they showed that treating mice with this protein improved their ability to use their forepaw in the first week after stroke. There were also indications that the protein changes the macrophage cells to a ‘pro-brain repair state’.

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.

About the research team

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

Impact

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 injury, with applicability to other types of brain injury, as well as neurodegenerative diseases.

Related projects

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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