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New function of CHIMERA adds severe impacts to aid researchers in studying traumatic brain injury

Asma Bashir and Cheryl Wellington at UBC.

Pictured: Dr. Asma Bashir (left) and Dr. Cheryl Wellington (right) following Dr. Bashir's successful PhD defense on December 13, 2019. Image source: Twitter/@her_science.

Traumatic brain injury occurs along a scale ranging from mild to severe, with damage occurring either cumulatively over a series of smaller impacts, to devastating accidents that can occur just once. Using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration), a model of head injury developed by Dr. Cheryl Wellington and colleagues, researchers have been studying the short- and long-term effects of traumatic brain injury (TBI); recent modifications to the platform have allowed Wellington lab researchers, including Dr. Asma Bashir, to study the cerebrovascular, behavioural and physiological effects of more severe TBI. 

The findings, published recently in the journal Experimental Neurology, speak to the value of CHIMERA as a tool for understanding a range of outcomes across the spectrum of brain injuries.

CHIMERA has been effective for studying mild TBI in mice, but researchers wanted to better understand the effects of serious TBI on the brain’s axons and blood vessels. Working with colleagues in the Department of Mechanical Engineering, the team designed and constructed an interface to study higher energy impacts mimicking moderate-severe human head trauma and its signatures in surrounding brain tissue, as well as in the blood.

The results showed cerebrovascular damage and elevations in tau in the blood. Tau is a protein that primarily accumulates in neurons in the brain and central nervous system, and has been implicated in neurodegenerative diseases including Alzheimer’s disease and Chronic Traumatic Encephalopathy, which is believed to be a potential long-term consequence of repeated concussions.

“We’re encouraged that we can see clear elevation of tau in the blood, which may serve as a biomarker for TBI; it is elevated in the blood at the six-hour mark post-TBI, which suggests tau could have clinical relevance in aiding diagnosis around the severity of a head injury,” said Dr. Bashir.

A follow-up behavioural study found deficits in spatial memory up to one month post-injury; changes in hippocampal synaptic function and inflammation within the brain’s grey matter were also observed.

For the Wellington lab, these findings are encouraging as they further reinforce the utility of CHIMERA as the top platform for studying TBI; now that the team can model a range of injury, from mild TBI to more severe head trauma, the platform can also be used to assess possible drugs and inform studies of long-term brain damage.

“This study validates CHIMERA as a versatile model of head injury and establishes the foundation for future research into TBI-induced changes in brain tissue, vasculature, and cognition and behavior,” said Dr. Bashir. Wellington lab researchers spent much of last year travelling to research facilities across North America and Japan to install the CHIMERA for researchers wanting to utilize the platform within their own labs, as CHIMERA is increasingly seen as one of the best tools for modelling human concussions using animal models in a lab environment.  

For Dr. Bashir, who completed the paper as a portion of her larger PhD thesis, this work represents the culmination of several years of effort to understand what happens to the brain after TBI.

“This paper sets the tone for future experiments, and will inform new questions and experiments about the mechanisms of brain changes after injury,” said Dr. Bashir, who recently completed her PhD and will begin a postdoctoral fellowship at the University of Edinburgh in February 2020.