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Understanding the role of blood vessel damage in traumatic brain injury

Project details

Dr Virginia Newcombe
University of Cambridge
Research area
Brain and spinal cord injury
Funding type
Project grant
Awarded in
October 2022


Traumatic brain injury (TBI) is a common cause of death and disability affecting people of all ages. There are no therapies capable of lessening the burden of the brain injury itself, and there has been little improvement in outcomes over the past two decades.

In this project, Dr Newcombe and colleagues aim to better characterise the injury to the brain, with a focus on injury to the blood vessels and changes to the way that the blood clots. This will guide the development of effective treatments.

Their two-part study draws on information from a European database that contains data on 400 brain-injured patients. And the team will recruit new 40 patients from the Neurocritical Care Unit at Addenbrooke's Hospital to take part in the second part of the study, which will use advanced MRI scanning and blood tests to find out more about the changes that take place in the injured brain.

Understanding how the changes seen on MRI in the acute and chronic phases after TBI relate to changes in clotting and blood vessel injury may help us to understand which patients may particularly benefit from therapies aimed at this subtype of injury.


Traumatic brain injury, frequently caused by falls and road traffic collisions, is a common cause of death and disability affecting people of all ages. It is the leading cause of death and disability in people aged one to 40 years.

We currently have no therapies capable of lessening the burden of the brain injury, and there has been little improvement in outcomes for brain-injured patients over the past two decades. Because TBI can occur at any age, the burden in terms of disability and loss of potential is enormous.

One of the problems in treating brain injury lies in the complexity and diversity of the injuries. The nature of the damage varies greatly between patients who may have overtly similar head injuries. Being able to characterise this damage will guide the development of effective treatments.

There is a growing awareness that injury to blood vessels within the brain contributes to the outcomes seen after TBI. It is also known that many patients with TBI are prone to bleeding, and this may be related to blood vessel (vascular) injuries. This is very relevant for TBI care, as continued bleeding in the brain is a common complication that leads to further irreversible damage and worse outcomes for patients. There is currently no treatment that prevents this bleeding.

“Traumatic brain injury continues to have enormous impact patients and their families.  Because TBI can occur at any age, the burden to society in loss of individual potential and productivity is immeasurable.  Yet we still have not made a major impact on new treatments to minimize disability.”  External reviewer


Dr Newcombe and colleagues want to understand the contribution that vascular injury makes to the outcomes seen after TBI.

Their study will have two phases. In the first, the team will use a database of over 400 patients from CENTER-TBI, a Europe-wide study, already curated and held at the University of Cambridge. The database contains extensive clinical information on these brain-injured patients, including MRI scans taken early (within three weeks of injury) and late (up to two years after injury).

The team will analyse the early and late MRI data to understand the consequences of vascular damage as well as damage to the white matter of the brain. They will relate the imaging data to patient outcome data and blood tests that indicate how severe brain injury is.

For the second part of the study, the team will recruit 40 patients with moderate to severe traumatic brain injuries from the Neurocritical Care Unit at Addenbrooke's Hospital. Blood tests and scans will be taken as soon as possible after the injury, and patients will be invited back for a second imaging session six months after injury to enable understanding of the long-term consequences.

Specifically, the team will:

  1. Use advanced MRI techniques to characterise the type and amount of vascular injury seen early and late after TBI.
  2. Assess whether there are detectable changes in the blood's ability to clot.
  3. Assess whether clotting changes are associated with the extent of injury found on the scans.
  4. Use the results to categorise patients into those with and without significant vascular injury, which will improve future clinical trial design.


The results from this study will give a better understanding of the extent and consequences of vascular injury following TBI. This will enable an improved estimate of injury severity, and potentially enable the selection of patients for targeted therapies.

If a link is proven with clotting abnormalities, existing drugs can then be tested in future trials and so potentially provide a targeted treatment to improve outcomes after TBI for the first time.

"This is an ambitious and innovative application from one of the leading investigators studying neuroimaging biomarkers in TBI.  There are many innovative and attractive features to this proposal, and the focus on TVI promises to open up new areas of therapeutic development." External reviewer

About the research team

This project will take advantage of a new collaboration between haematology and neuroimaging experts to answer key questions about traumatic vascular injury not previously possible.

The research environment in Cambridge and concentration of expertise in acute brain injury research and facilities is unrivalled anywhere in the world, and enables the team to address new research questions in a unique way.

The team is led by Dr Virginia Newcombe, an expert in Neurocritical Care, and she will build on previous successful collaborations with partners at Imperial College London, the University of Oxford and Aalborg University Hospital in Denmark to deliver this ambitious project.

“The research team and centre are outstanding on an international level.  The combination of the clinical and imaging infrastructure is rare.” External reviewer

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