Humanised model of brain injury to study tissue damage and repair

The Problem

About 1 million people in the UK visit A&E each year with some form of head injury, whether due to road traffic accidents, assaults, falls, or other accidents at home or at work. Our brains heal slowly, and most people will have no lasting effects, but many others will be left with a traumatic brain injury that can have a devastating and lifelong impact on them.

Research to develop and test new treatments, such as protective drugs and electrical stimulation, depends on creating injuries in living animals, and are among the most invasive procedures in experimental research. Because brain injuries can be of different severity, animal ‘models’ of different severity are also used.

Hundreds of papers have been published describing thousands of mice and rats subjected to traumatic head injuries by cutting or crushing the brain tissue, causing pain and suffering, and often paralysis and infection.

To mimic a brain injury in a dish is difficult because cell-based models are often too simple:
• They don’t usually have all the cell types of the nervous system (including immune cells).
• It’s difficult to create ‘injuries’ in these models.
• Most models can’t re-create the complicated events that occur after injury, such as scarring and inflow of immune cells.
• Monitoring injury and repair using imaging tools is technically challenging.

Pictured: Prof Divya Maitreyi Chari (centre) with Dr Stuart Jenkins and Dr Christopher Adams, along with lab members Rux Birea, Celeste Musasa, Zoe Dombros Ryan, Jack Griffiths and Emily Franks

The Project

The Neural Tissue Engineering Keele (NTEK) group, led by Divya, with Dr Christopher Adams, have developed a new, high throughput, and technically easy model of neurological injury in a dish, using mouse brain cells. They have created a brain tissue-mimetic network in a jelly-like matrix which contains all the major nervous system cells.

Processes like scarring, immune cell reactions and stem and/or progenitor cell migration can all be replicated in this system. They also know that important brain development events such as formation of protective sheaths around nerve cells, and electrical maturation of nerve cells can happen in this model.

Working with Professor Harish Poptani at the Liverpool Centre for Preclinical Imaging, the Keele NTEK group will re-develop the model using off-the-shelf human cells and see if imaging methods used in clinical diagnosis can be used to ‘see’ injury and repair in the model.

If this is possible, they can develop a sophisticated and advanced model of brain injury for medical research and new therapy development.

The Potential

If successful, it will allow for the first time, non-invasive clinical imaging methods used in patients, to be applied to the study of 3D dish injury models without reliance on animals or products derived from animals.

This will give the neuroscience and tissue engineering research community, a new human-specific way to study brain injury and therapeutic interventions without relying on recreating brain injuries in animals.