Researchers have created a traumatic brain injury (TBI) computer model that maps blood vessels in a rat brain in the highest resolution yet.
The team at Imperial College London say the models could help improve understanding of how blood vessels are affected by TBI, as well as its effects on the protective layer encasing them known as the blood-brain barrier (BBB), which protects the brain from harmful circulating molecules and pathogens.
If the methods translate well onto human brains, Imperial say they could also help improve understanding of how TBIs develop and how best to treat and protect against them.
The simulations could even help to replace animal models of TBI, potentially reducing the use of animals in brain research.
TBIs are the most common cause of chronic disability in under 40-year-olds and result from severe blows or jolts to the head.
Beginning at the site of impact, mechanical forces travel in waves through the brain, twisting, stretching, and shearing brain structures as the injury cascades. These forces are known to affect blood vessels, but the finer details of the relationship between mechanical forces and vascular injury are yet to be established.
Now, researchers at Imperial have created a computer model of TBI which maps the network of vessels in the brain – called the vasculature – in the highest resolution yet, incorporating rat brain vessels just 10 microns in diameter.
Using the models, they found that adjacent blood vessels sustain profoundly different levels of stress depending on their alignment with neighbouring ones.
Blood vessels at 90 degree angles to others were less likely to be damaged, and vessels could be stretched to up to 14 per cent of their original length without injury, while stretching by more than this amount would result in injury.
Lead author Dr Siamak Khosroshahi, who conducted the work while at Imperial’s Dyson School of Design Engineering, says: “Our unique approach explains the unrecognised role of the vascular anatomy and shear stresses in how large forces cascade through the brain. This new understanding could contribute to improving TBI diagnosis and prevention.”
The degree to which the BBB lets molecules into the brain is known as permeability. The barrier can become more permeable after injury, making it more likely to let pro-inflammatory molecules reach the brain and usher in further injury.
By using rat models of TBI, the authors demonstrated that greater BBB permeability occurs in TBI as a result of disruption of the vasculature, and that this is most evident soon after injury.
From this information they created brain models digitally in high enough resolution to highlight the vasculature. They found that the computer models allowed them to accurately predict the distribution of stress in the small blood vessels of the rat brains. The models also allowed them to slow down time to look at the details of TBI more closely.
Senior author Dr Mazdak Ghajari, also of Imperial’s Dyson School of Design Engineering, says: “Injury happens in a fraction of a second, making it hard to observe exactly what goes on. By slowing down the process, we can pinpoint exactly which brain areas sustain the most damage and go some way to understanding why.”
The new, high resolution computer simulations could provide a blueprint for studying TBIs using more computers and fewer animal models, in line with the principles of Replacement, Reduction and Refinement (the 3Rs) in animal research.
The researchers say their models could also provide a more objective way to assess protection systems like helmets. Future studies on humans that include detailed reconstructions of the biomechanics of TBI are also needed to confirm the findings before using them to predict injury risk in humans.
The improved understanding of the BBB could also help further research into drug delivery of brain-specific medicines.
PFA leaders pledge to donate brain to Concussion Legacy Project
Two senior figures at the PFA have pledged to donate their brain to research as part of the pioneering Concussion Legacy Project to protect future generations of players.
PFA Chief Executive Maheta Molango and PFA Chair John Mousinho have both made the pledge through a partnership with the Concussion Legacy Foundation UK, following the lead of England Rugby World Cup winner Steve Thompson.
The Concussion Legacy Project, unveiled yesterday, will research Chronic Traumatic Encephalopathy (CTE) and other consequences of brain trauma in athletes and military veterans in the UK.
PFA Chief Executive Molango, a former striker at Brighton & Hove Albion, Lincoln City and Oldham Athletic, said: “While being very mindful of taking immediate steps to protect current players, in the long-term ongoing research is vital to enable us to be able to answer more questions and best support members.
“We have been listening and engaging with leading academic experts, and they tell us that brain donation is a key piece to the puzzle in understanding CTE. We are excited to join a global network of the most prominent researchers in this area.”
Yesterday, Steve Thompson became the first athlete to pledge to the Concussion Legacy Project’s Brain Bank, with the former Lion previously stating that he cannot remember playing in England’s 2003 World Cup final win over Australia.
Today, Oxford United’s captain Mousinho, who has amassed over 500 league appearances over a fifteen-year professional career, committed his support for the project.
PFA Chair Mousinho explained: “Brain donation is an intensely personal decision for former players and their families. However, I have been inspired by the team at the Concussion Legacy Foundation and The Jeff Astle Foundation, and I have decided to commit my brain to future research in the hope that it can help play a part in protecting future generations.
“The Concussion Legacy Foundation has a strong ethos of supporting families and everyone affected by brain injury, and they are values we share at the PFA.”
Dawn Astle, who has been campaigning for two decades for football’s authorities to publicly recognise a link between the repeated heading of a football and dementia in later life, has given her full support to the new concussion initiative.
Speaking on behalf of The Jeff Astle Foundation, she said: “Brain donation is the most valuable gift of all for future generations of footballers. It may be many years before this jigsaw is complete but adding each piece, one at a time is the only way we will understand the true picture and make a better future for others.
“The Jeff Astle Foundation encourages families of athletes and veterans to donate the brain of their loved one to the Concussion Legacy Project at PledgeMyBrain.org.”
‘We want to be part of the solution – for Bill and future generations’
Dr Judith Gates speaks to NR Times about this weekend’s football match organised by Head for Change, which will be the first ever to involve no heading of the ball
The first football match which involves no heading of the ball will help raise awareness and stimulate conversation about the impact of head injury in sport, its organisers have said.
The 11-a-side match, involving 25 former professional footballers, has been hailed as an experiment as researchers try to discover whether the game can function without heading, in light of ever-growing research which links football to neurodegenerative disease.
It is organised by Head for Change, the organisation helping to drive forward calls for changes to player safety, and will only allow headers in the penalty box for the first half and then restrict all heading during the second half.
It will be held at Spennymoor Town Football Club, in County Durham, on Sunday at 3pm.
The event forms part of the “legacy” for former Spennymoor Town and Middlesbrough defender Bill Gates, who has sports-related dementia, and whose wife Dr Judith Gates is co-founder and chair of Head for Change.
“When Bill received his diagnosis in 2017, we made two promises to him,” Dr Gates tells NR Times.
“One was to optimise his life and do all we could to make his life as good as we could as a dad, grandad and great grandad, and the second was for his legacy, to do everything we could to be part of the solution for future generations of footballers and their families not to have to face this.
“The purpose of this match is to raise awareness of the dangers of heading the ball and to provide alternative discussion with purpose. It’s an experiment to see what the game will look like.
“To be clear, Head for Change is not suggesting heading should be banned, that is a decision for football’s governing authorities, not for us.
“But we want people to realise the impact. Bill was a Titan to me in his 20s, fit and indestructible, so if this disease can do this to him, it can happen to anyone.”
The match has attracted widespread media attention and comes after an array of stark academic findings, including the research from Professor Willie Stewart that footballers are up to five times more likely to suffer from dementia than the general population.
“Part of why I co-founded Head for Change was to be part of the solution,” says Dr Gates.
“We’re extremely aware that there is a lot of bashing going on and everyone is saying it’s someone else’s fault, but lessons must be learnt from the past.
“For too long we have been assured that our brain was safe in our skull, but we are increasingly understanding how the brain works and how it can be damaged through contact sports. Education will continue to play a very important role in what happens going forward.”
The match itself – which will also be raising money for The Solan Connor Fawcett Cancer Trust – will be held at Spennymoor Town’s stadium, The Brewery Field.
The town is where Dr Gates grew up and met her husband, and in a quirk of fate, Spennymoor Town’s chief executive Brad Groves used to work for Bill as a warehouseman when Bill owned a chain of sports stores.
The club, alongside those playing in the match, have been hugely supportive of their ambitions, says Dr Gates.
“We’ve been amazed at the extent to which they have stepped up, Spennymoor have been phenomenal. Brad has been so kind in offering whatever he can do to help. We are hugely appreciative,” she says.
“The players taking part are excited to be part of it, they may not be able to use one of their many footballing skills but they can use the rest of them.
“Spennymoor is a small town with a big heart and we are so pleased to be able to hold this match, and particularly here, at Bill’s first club.”
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