CHIMERA model produces surprising results in concussion study

MRI of concussion (human brain).

Pictured: an MRI scan of a human brain after concussion. Image source: iStock.

Dr. Tom Cheng was surprised to discover that the effects of repeated concussions can last much longer than originally thought. In a paper published recently in the journal Alzheimer’s Research & Therapy, Dr. Cheng, a postdoctoral fellow in Dr. Cheryl Wellington’s lab, and colleagues found that repeated mild traumatic brain injuries (mTBI) affected spatial learning and memory in mice for up to almost a year post-concussion. In mice with Alzheimer’s disease-like pathology, concussion reduced the brain’s ability to extinguish fear memory, leading to behaviours suggesting post-traumatic stress disorder (PTSD).

“Using CHIMERA, we’ve demonstrated that repetitive concussions in animals can lead to significant inflammation and damage of brain tissue, and observable deficits in motor and cognitive behavior,” said Dr. Cheng. “After two concussions and a recovery period of eight months, we were still able to detect inflammation and tissue damage.”

Collaboration between Dr. Wellington and the Department of Mechanical Engineering’s Dr. Peter Cripton has resulted in a unique model of concussion called CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration), which provides conditions that are clinically similar to traumatic brain injury (TBI). CHIMERA reproduces concussion-like injuries using a mechanically precise impact that leads to unrestricted head rotation, similar to most human concussions. CHIMERA is a unique tool in that allows researchers to induce a concussion-like experience in animal models and study the impacts over a long-term period.

The long-term effects of moderate and severe TBI include a range of psychiatric symptoms, including anxiety and depression, and can include cognitive impairments and dementia. Every year, 165,000 Canadians are affected by TBI with injuries spanning a spectrum of mild, moderate, and severe. While research into the serious impacts of moderate to severe TBI is robust, the long-term implications of mTBI, representing 80 per cent of all TBI cases, are less well-understood; according to Cheng et al, up to 55 per cent of those affected by mTBI report symptoms that persist between three and 12 months after injury.

“Our earlier research has shown that CHIMERA is a reliable model of injury, and in this case we can see that our findings in mice mirror the clinical literature for human TBI,” said Dr. Cheng. “Our hope is that we can continue to learn more about how TBI affects the brain in the short and long term, and that our current trajectory will lead to our ability to test potential treatments for traumatic brain injury.”

The value in CHIMERA has spread beyond the University of British Columbia, and this cross-faculty innovation is beginning to find homes in labs around the world.

“Going forward, we’ll need to look at the mechanisms behind behavioural changes following mTBI. We still have much to learn, but we are encouraged that CHIMERA continues to be a useful model of TBI and its effects on brain pathology,” said Dr. Cheng.

"Everyone in the Wellington and Cripton labs are thrilled with how well the CHIMERA program is growing since we first started this interdisciplinary collaboration in 2013," said Dr. Wellington. "Tom’s latest paper provides some very intriguing insights into the long-term consequences of concussion, and gives us much food for thought for additional studies on the relationship between TBI and PTSD. We are grateful to UBC and our funders for helping us realize the vision of creating a truly translational animal model of traumatic brain injury and look forward to many more exciting discoveries in the near future."