APAGBI Small Research Grant

The effect of xenon-treatment on the developing brain following paediatric neurotrauma

Dr Robert Dickinson

Head Injury (Traumatic Brain Injury or TBI) is one of the most common causes of death and disability in children in the UK and worldwide. Children who experience a head injury often suffer from long-term disability and complications including difficulties in learning and memory, impaired movement (locomotor function) and epilepsy (or "fits"). Unlike head injury in adults, traumatic brain injury in children (paediatric TBI) affects a brain that is still developing. Worryingly, head injury in children is associated with a worse outcome than in adults. Current treatment for head injury in both adults and children is mainly supportive and there are no treatments specifically targeting the loss of brain cells that occurs following a head injury. Our laboratory has recently shown for the first time that xenon, a gas used as a general anaesthetic, can limit the development of injury and brain cell death and improve survival after traumatic brain injury in adult mice.

This project aims to test the hypothesis that xenon will reduce the development of injury in the first 24 hours after TBI in paediatric rats and that this will result in an improvement in learning and memory, locomotor function and reduced anxiety in adulthood.

We will use a well-established laboratory model of blunt traumatic brain injury (the most common type of TBI caused for example by falls or a blow to the head) in rodents. We have already used this model (called the controlled cortical impact model) to show that xenon protects against brain injury in adult mice. Paediatric rats (aged 21 days) are a similar size to adult mice, therefore the same equipment can be used. We will measure the size of the 'contusion' (bruise of the brain) in animals with and without xenon treatment in one group. Another group will be allowed to grow to adulthood following TBI and we will then perform behavioural tests of learning, memory and movement in these adult animals.

Expected outcomes
We expect that xenon-treatment will reduce injury development following TBI in paediatric rats. We expect that untreated rats that had paediatric TBI will have impairments in locomotor function, learning and memory, and anxiety and that xenon treatment will prevent or reduce these impairments. The ultimate aim of this project is the use of xenon in TBI in humans. If this project is successful then it may lead to clinical trials of xenon as a treatment for head injury in children.