New research has revealed potential for the development of therapies which could help safeguard against cognitive decline and depression post-concussion.
The study in mice clarified the role of specific immune cells in the brain that contribute to chronic inflammation.
Using a technique called forced cell turnover, researchers eliminated these cells in the injured brains of mice for a week and then let them repopulate for two weeks.
Compared to brain injured mice recovering naturally, mice that were given the intervention showed less inflammation in the brain and fewer signs of thinking problems 30 days after the injury.
Although temporarily clearing away these cells, called microglia, in humans is not feasible, the findings shed light on pathways to target that could lower the brain’s overall inflammatory profile after a concussion, potentially reducing the risk for behavioural and cognitive problems long after the injury.
“It’s almost like hitting the reset button,” said senior study author Jonathan Godbout, professor of neuroscience in The Ohio State University College of Medicine.
“In a moderate brain injury, if the CT scan doesn’t show damage, patients go home with a concussion protocol. Sometimes people come back weeks, months later with neuropsychiatric issues. It’s a huge problem affecting millions of people.
“How do you treat that? At least in mice, by turning over the microglia in the brain we had a very positive effect on their behaviour, cognitive status and level of inflammation in the brain.
“Now we can focus on cellular pathways that generate chronic inflammation as a target.”
About 85 per cent of traumatic brain injuries are similar to the type of concussion examined in this study, involving dispersed impact to the head that causes brain tissue to bump against the skull.
Previous research suggests that at least 75 per cent of people who experience a moderate brain injury have long-term mental health and cognitive complications.
Professor Godbout’s lab has previously linked depressive symptoms in mice to microglia’s sustained ‘high alert’ status after a head injury, which causes the cells to overreact to later challenges to the immune system and become excessively inflammatory.
In a more recent study in mice, his team showed that forced turnover of microglia before a head injury could reduce later neuropsychiatric complications.
“That was a proof of principle to show that a lot of the inflammation, especially in the long term, is mediated by microglia,” he said.
“But there is an acute phase of inflammation – you want to initiate that repair process.
“There’s a positive to that early inflammatory response in the brain or spinal cord. If it lasts a long time and doesn’t fully resolve, that’s when it’s dangerous.”
In this new study, researchers waited for seven days after the brain injury to force the turnover of microglia, giving the cells time to carry out their work promoting initial healing.
An experimental drug that inhibits a protein that microglia in mice need for survival was added to their food for a week, resulting in depletion of over 95 per cent of microglia in their brains.
After allowing 16 days for the microglia to repopulate, researchers compared the intervention mice to injured mice that recovered without the cell turnover treatment.
The intervention mice performed better than control mice on tasks testing their memory and depressive symptoms.
Further analyses of injured brain tissue suggested the cell turnover reversed some injury-related damage to neurons, lowered overall inflammation and improved the brain’s ability to adapt to change.
Researchers also injected mice with a molecule that triggers an immune response to mimic an infection, and found that sickness behaviour was lower in the intervention mice.
Prof Godbout said these combined findings suggest that the repopulating microglia returned in a less “primed” state of readiness, lowering chances for a lifetime of exaggerated inflammatory responses in the brain to any challenge to the immune system – that brain inflammation being the likely culprit behind the neuropsychiatric complications that follow a head injury.
“If microglia in the human brain don’t return to normal and chronic inflammation persists after a head injury, it’s not just a secondary brain injury that causes problems,” said Prof Godbout.
“Even getting a viral infection after concussion recovery can progress into a cognitive or behavioral issue or amplify some other part of behaviour, like depression.
“There is a real connection between a head injury and mental health, and the risk doesn’t go away.
“Now we’re looking more closely at the pathways that cause changes in microglia, and targeting something specific in that pathway. That is a way forward.”
Brain injury survivor fundraises for The Walton Centre
Karen Parry’s running club is fundraising for the specialist centre which saved her life
A woman whose life was saved by The Walton Centre after an accident at home has inspired a fundraising initiative on behalf of the nationally-renowned specialist centre.
In December last year, Karen Parry was making her way up to bed when she fell down the stairs, hitting her head on the hall floor.
Karen, from Prescot, was rushed to the Aintree Trauma Unit before being transferred to the neighbouring Walton Centre for life-saving brain surgery.
“It was one of the most terrifying nights of my life,” recalls Karen’s husband, Gavin.
“Karen was badly hurt, but I didn’t realise how badly until I was at The Walton Centre speaking to the anaesthetist about the emergency surgery she was going to have.
“Mr Rasheed Zakaria and his surgical team saved Karen’s life, but they also took the time to calmly and compassionately explain Karen’s condition to me along with the steps they would be taking.”
Karen made it through the surgery at the pioneering Walton Centre and was put in a medically-induced coma to allow her brain to recover enough to be woken up later.
“I was visiting Karen in ICU every day with special permission due to the severity of Karen’s condition,” Gavin continues.
“When I came in the day she was being brought out of her coma, I found her dedicated nurse brushing her hair, she said it was because removing the tangles would have hurt her when she was awake.
“I thought this was very kind and thoughtful. They cared so well for her, it was outstanding.”
The 52-year-old spent over two weeks in ICU, having further corrective procedures before moving to a ward to recover further – spending Christmas in hospital.
Gavin said: “Karen had been assisted into the chair at the side of her bed for our visit, which was great to see.
“At this stage Karen was too weak to spend much much more than half an hour sat upright and we were all really happy to be with each other.
“It was a lovely visit and we were sad to leave. As on any other day the staff were busy but lovely and kind.”
Then March this year, Karen was able to return home, after receiving rehabilitation with the Cheshire and Merseyside Rehab Network, hosted by The Walton Centre.
“Karen was so determined to get better, she’s so tough,” said Gavin.
“She kept getting stronger. The Walton Centre continued to support her. Mr Zakaria, the neurosurgeon who saved her life, sent a detailed letter to her GP to ensure they knew exactly how to support Karen when she did come home.”
While Karen was in hospital, her local running club Knowsley Harriers nominated The Walton Centre Charity as their charity of the year.
Karen is Treasurer of the club and an avid running coach. Each month the club hosts ‘The Walton Centre Charity’ 5km run, which encourages members and non-members to donate to the charity.
So far they have raised nearly £900 this year, and will continue to do so for the rest of 2022.
Gavin added: “The club has a number of links to the hospital, from other members who have previously been looked after there. We were delighted when they picked The Walton Centre Charity.
“This was a very frightening time for my son and myself and very much a rollercoaster ride of emotions explained to us when Karen entered the unit.
“Sadly, Karen remembers very little of her time in The Walton Centre but I have reminded her of the wonderful care which she has received.
“The nurses, doctors and therapy staff are truly inspirational, not only for their professionalism and incredible skills as medical practitioners but they also have the kind of qualities that cannot be taught in a classroom – care, love, kindness, understanding and humanity – they have them in abundance.”
Karen said: “Sadly, I remember little about my time in The Walton Centre due to the nature of my head injury. Gav has spoken to me at length about the wonderful people that cared for me there. I would just like to thank them all from the bottom of my heart.”
To donate to the fundraising appeal, visit https://www.justgiving.com/fundraising/khac2022
Fact-finding tour helps creation of ABI Strategy
Chris Bryant MP and UKABIF visit three key neuro-rehab sites nationally
Efforts to gather information which will help in the creation of the new Acquired Brain Injury (ABI) Strategy have been boosted through Chris Bryant MP’s visits to key neuro-rehabilitation sites around the country.
The MP – chair of the All Party Parliamentary Group (APPG) on ABI, who has been instrumental in securing the go-ahead from the Government to create the Strategy – visited sites in Newcastle, Sheffield and Birmingham to gain greater insight into what provision exists and what more is needed.
The Strategy has been hailed as being of vital importance in helping to support people living with brain injury and to help level the disparity in provision across the country.
Chris – also co-chair of the ABI Strategy Programme Board – visited Walkergate Park in Newcastle with UKABIF’s chief executive, Chloe Hayward, who is co-chair of the Strategy’s Patient and Public Voice Reference Group.
The Tyneside centre provides neuro-rehabilitation and neuropsychiatry services for adults with a disability caused by injury or disease affecting the brain or spinal cord.
They met with staff and patients at the 64-bed centre, learning about the range of rehabilitation offered by its specialist neuro-rehab team, and the equipment and technology available to help people affected by ABI to live as independently as possible.
In Sheffield, they visited Steps rehabilitation centre, which provides 23 rooms for residential rehabilitation, and offers everything from hydrotherapy to music therapy, alongside the latest technology to benefit patients’ lives.
On their trip to Birmingham Women and Children’s Hospital, to see what rehabilitation services are available for children, Chris met with staff, patients and families on a tour of the city centre hospital and also spoke with The Child Brain Injury Trust.
At each location, staff and patients were given the opportunity to say what they thought was needed to improve the lives of those living with ABI.
“These visits have been hugely helpful as we look to gather information and first hand views from people working in ABI neuro-rehabilitation,” said Chris, whose Private Members’ Bill led to the Government granting approval for the creation of the ABI Strategy.
“If the ABI Strategy is to be fit for purpose, we need to know what is currently working, but perhaps more importantly, what isn’t working in order to ensure the needs of people with an ABI are properly addressed.
“I want to say a huge thank you to everyone we met for sharing their experiences for us to consider as we take the Strategy forward.
Chloe Hayward said: “Being able to see and speak to both staff and patients means we have real life experiences from people.
“As co-chair of the Strategy’s Patient and Public Voice Reference Group, I want to make sure patients’ views are taken into consideration when the Strategy is being established.”
New therapy reduces veteran headaches after brain injury
Cognitive Behavioural Therapy for Headache also shown to have positive impact on PTSD symptoms
The first therapy to be developed specifically for post-traumatic headaches significantly reduced related disability in veterans following a traumatic brain injury (TBI), a study has revealed.
Cognitive Behavioural Therapy for Headache (CBTH) was also shown to reduce co-occurring symptoms of post-traumatic stress disorder (PTSD) comparably to a gold-standard PTSD treatment.
Furthermore, the therapy was shown to be appealing to patients with low drop-out rates, and is easy for therapists to learn and deliver, increasing its potential to be widely used and to improve the lives of servicemen and women and veterans globally.
CBTH, which uses cognitive behavioural therapy concepts to reduce headache disability and improve mood, includes key components such as relaxation, setting goals for activities patients want to resume, and planning for those situations.
“We are excited by this development in the treatment of post-traumatic headache, which along with TBI is poorly understood and for which treatment options are so limited,” said Dr Don McGeary, associate professor at The University of Texas Health Science Center at San Antonio (UT Health San Antonio).
“To find the first major treatment success for post-traumatic headache, which is arguably the most debilitating symptom of TBI, and that the treatment also significantly reduces co-morbid PTSD symptoms, is a major breakthrough.”
Both TBI and PTSD are prevalent in post-9/11 military conflicts, and the two conditions commonly occur together.
Post-traumatic headaches, or headaches that develop or worsen following a head or neck injury, become chronic and debilitating in a large percentage of those who experience a TBI such as a concussion, inhibiting their ability to engage in the activities of daily life.
When PTSD is co-occurring, it can worsen the headaches and make them more difficult to treat.
Effective treatments exist for PTSD but not for post-traumatic headache, which along with TBI, scientists are still working to understand.
Migraine medications commonly used to alleviate the headache pain do not relieve related disability. They also often have unwanted side effects, and their overuse can worsen headaches.
In the study, Dr McGeary and his team developed CBTH by modifying a psychotherapy for migraine headaches. They evaluated its efficacy with co-occurring post-traumatic headache and PTSD symptoms.
The study was conducted at the Polytrauma Rehabilitation Center of the South Texas Veterans Health Care System.
Participants had clinically significant PTSD symptoms and headaches persisting more than three months following a TBI. They were randomly assigned to receive either CBTH, a leading PTSD treatment called Cognitive Processing Therapy (CPT), or the usual care provided at the VA Polytrauma Center.
At the end of treatment, researchers found that, compared to usual care, those receiving CBTH reported significant reductions in disability and in negative impact on function and quality of daily life.
They also showed improvement in PTSD symptoms comparable to the group that received CPT. All of these treatment gains were maintained six months after treatment completion.
CPT, on the other hand, led to significant and lasting improvements in PTSD symptoms, but on its own did not improve headache disability.
“This was a surprise,” said Dr McGeary.
“If theories about PTSD driving post-traumatic headache are correct, you’d expect CPT to help both PTSD and headache. Our findings call that into question.”
Interestingly, CBTH did not reduce headache intensity or frequency compared to usual care.
Dr McGeary said its dramatic reductions on negative life impact are likely due to its building patients’ confidence that they could control or manage their headaches, a concept known as “self-efficacy.”
That sense of control was key to helping patients “get their lives back,” he said.
“If you can improve a person’s belief that they can control their headache, they function better,” Dr McGeary said.
“That’s because, when dealing with a long-term, disabling pain condition, people make decisions about whether they’re going to actively engage in any kind of activity, especially if the activity exacerbates the pain condition.
“They make those decisions based on their perceptions of their ability to handle their pain.”
In comparison to CPT, CBTH requires fewer and shorter therapy sessions—typically eight sessions of 30-45 minutes each. CPT typically involves 12 sessions lasting 60-90 minutes each.
CBTH requires only two hours to train clinicians to deliver the therapy, compared to CPT, a complex treatment that requires significant training and acquired skill.
The research team now hope to broaden their study to be as representative as possible.
Dr McGeary said: “We need more women, more racial and ethnic diversity, veterans as well as active military of different branches, with varying comorbidities, in different geographic regions attached to different hospitals and medical systems because we’re comparing to usual care.”
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