Brain Blood Flow Regulation After Brain Injury

Hello everyone. A massive appreciation to Tamin and Sam for all their help in organizing this session. On behalf of Paul, myself, and the other members of our research group, we are delighted to contribute to this webinar series. We are really pleased to talk about some of our research in this space and will try to keep things accessible, which is sometimes difficult for researchers with very niche interests in physiology. If you have any questions that we do not get to in the Q&A at the end, you can see my email address and Paul's email address on the screen; we would be delighted to answer any questions over email as well.

Paul and I are part of the ExHIBIT research group at the University of Exeter. ExHIBIT stands for the Exeter Head Impact, Brain Injury and Trauma research group. We are a collective of scientists with a range of skills and interests, which allows us to do multidisciplinary research and look at head impacts from a variety of different angles. I am mostly interested in vascular function, specifically cerebrovascular function, which is the health of the network of blood vessels that feed the brain. Paul is much more interested in neurometabolism, or how the brain is fueled. We also have other members of staff interested in motor control and whether we can measure movement as a way of diagnosing changes in brain function.

As a vascular physiologist, my research group is interested in how lifestyle exposures—such as exercise, diet, sleep, and head impacts—might increase or alter your risk of chronic cardiovascular disease, including vascular dementia. Vascular dementia involves a known blood vessel element that progresses over the lifespan. Today, we are focusing on head impacts and how they affect brain blood flow regulation.

We know that brain blood flow regulation is altered in people who have had a traumatic brain injury (TBI). It can be slightly unhelpful to lump all TBIs together, and the same is true for concussions. I am interested in these impacts, including subconcussive head impacts, which are the impacts that do not lead to an overt concussion. Concussion is hard to measure and can sometimes be a silent injury. We measure aspects of cerebrovascular health in my lab, such as neurovascular coupling and autoregulation.

An area of public concern at the moment is how heading in football relates to dementia risk. No one is getting concussed from the act of heading a football itself, making it a prime example of subconcussive impact. However, the 1966 World Cup winner Nobby Stiles, who died in 2020, had advanced dementia and chronic traumatic encephalopathy (CTE), which led to widespread discussion about the dangers of heading. Research from Professor Willie Stewart’s lab in Scotland has shown that professional footballers from the 1970s were three and a half times more likely to die from neurodegenerative disease and were five times more likely to have dementia-related medication. Interestingly, goalkeepers were only about half as likely to require such medication, suggesting that the act of heading is a significant factor. Due to these concerns, the English FA has moved to ban heading in training for children and recently made it an offense to head the ball in certain contexts.

In our lab, we use an ultrasound technique to measure the velocity of blood flow through the brain. When we head a football, the brain—which is suspended in fluid—might move inside the skull, potentially causing a counter-coup injury. The back of the brain is involved in vision, which is why a blow to the head might make you 'see stars.' We use a visual search task to observe blood flow responses in the back of the brain. Research has shown that neurovascular coupling is altered after repeated heading, which indicates silent changes occurring in the brain. We also conducted a study including women football players, noting that women often experience greater head acceleration during heading, likely due to lower neck strength. While our study of six headers over an hour did not show changes in neurovascular coupling, it highlights the need to continue investigating these long-term, repeated exposures.

We also study autoregulation, which is the body's ability to maintain constant brain blood flow despite changes in blood pressure, such as when you stand up. We know this ability is altered in people who have had concussions. We used a squat-stand maneuver to observe this in a university boxing squad. We found that after three rounds of boxing, the participants’ ability to regulate brain blood flow was slower than before, even though their cognitive function appeared normal. This suggests a silent process that only specialized measurement can detect.

I will now hand over to Paul to talk about neurometabolism and our research on supporting brain health.

Thank you, Bert. Before I started researching traumatic brain injuries, I was a diabetes researcher looking at how low brain blood sugar affects the brain. I switched to TBI research because I play American football and wanted to understand the risks better. About a million people in the UK suffer from acquired brain injuries, a number comparable to those with dementia.

Your brain has a sweet tooth; it represents about 2% of your body weight but uses 20% of your daily calories, primarily in the form of sugar. This energy is delivered by blood, so if blood flow is disrupted, energy metabolism is also disrupted. Research in rodents shows that after a head injury, the brain's ability to take up sugar decreases. We think this leads to a brain energy deficit in humans, which might contribute to long-term issues.

We are looking at whether we can improve brain function after injury using alternative fuel sources, specifically ketones. Ketones are produced naturally during starvation, but they can also be taken as supplements. Evidence suggests that ketones can improve brain function in cases like Alzheimer's disease. We are currently conducting a study with American football players, providing them with a ketogenic supplement immediately after a game to see if it supports recovery and helps mitigate the brain energy deficit. While it is early days, the results are promising.

Beyond ketones, we are also looking at creatine and vitamin B12, which have shown potential in supporting brain function post-concussion. We are also exploring drug options to improve mitochondrial function, as mitochondria are the powerhouses of your cells. To summarize, the brain is an adaptable organ. If we can fuel it properly, we can help it help itself. We are spending time unpicking why energy systems are disrupted so we can develop targeted, drug-like approaches to support brain energy following injury. Please feel free to email us with any questions.