"Epilepsy is a debilitating neurological disorder, with multiple causes. Currently, treatment for epilepsy includes only drugs which control seizures, rather than tackling the underlying causes. Further, approximately 30% of epilepsy patients are resistant to all available drugs. Epilepsy which develops following an acute insult to the brain, such as a seizure or head injury are particularly commonly associated with resistance to drugs. Understanding the processes which lead to the brain becoming chronically epileptic and the causes of drug resistance is important for developing solutions.
When the brain is mechanically injured, deprived of oxygen, deprived of blood or hyperexcited, ATP, a molecule involved in providing energy to cells, is released into the extracellular space. Here, it acts as a trigger for inflammation which is important for limiting damage to local sites, killing pathogens, removing debris from damage, etc. Inflammation, however, when chronic, can contribute to pathology. It has previously been demonstrated that inflammation contributes to the development of epilepsy and is involved in resistance to antiepileptic treatments.
The purpose of this project was to investigate the contribution of ATP to this process via the ATP receptor, P2X7, which has been widely reported as a ""gatekeeper"" of inflammation. This has involved characterizing ATP release in the brain during and following seizures and investigating the contribution of P2X7 to epilepsy and resistance to anti-convulsants, using an array of transgenic mice and P2X7-targeting drugs. The overall objective of the project was to characterise the role of the ATP-P2X7 axis in drug-resistance and development of epilepsy and test methods for potentially intervening."
