What cellular processes help to stop seizures?
ENDEAVOUR PROJECT GRANT
£174,700
Professor Andrew Trevelyan
Newcastle University
Most seizures stop on their own without any medical help. This suggests that the brain has natural anti-seizure mechanisms, but we still do not fully understand what these are or how they work. One possible explanation is a phenomenon called cortical spreading depression (CSD) – a wave of activity that travels through the brain and has been observed at the end of seizures. However, CSD may be a double-edged sword: while it could help end seizures, it has also been linked to SUDEP (sudden unexpected death in epilepsy). Understanding exactly how seizures stop, and whether CSD plays a protective or harmful role, is vital for improving outcomes in people with epilepsy.
"The vast majority of seizures stop without any medical intervention, which does imply that there are anti-seizure mechanisms hard-wired into the brain, although we still do not know how this happens. We believe we might now have discovered the answer, and we will test this new theory, supported by the Epilepsy Research Institute
This study will investigate how seizures naturally stop, with a focus on cortical spreading depressions. The team recently discovered a new way to trigger CSDs in the lab, offering a fresh perspective on how they arise. The researchers believe that during a seizure, ions flood into brain cells and put them at risk of bursting. The brain may respond by triggering a protective mechanism – CSD – to prevent this. However, in some cases, this response may spread too far, potentially contributing to SUDEP.
Using their new experimental model, the team will closely examine what happens inside neurons during and after seizures. They aim to identify the molecular triggers caused by CSD and how this process might both stop seizures and, in some cases, cause harm. This work may also lead to the development of new medicines that can safely stop seizures and reduce the risk of SUDEP.
This research tackles one of the biggest unanswered questions in epilepsy: how seizures end naturally. Shorter-term benefits include identifying molecules that make brain cells vulnerable during seizures, leading to new drug targets. The work may also result in new tools to test epilepsy treatments and a computer model to simulate seizure activity. Understanding more about how seizures stop could be transformational in the long-term, as it may reveal new treatment strategies that work with the brain’s natural defences to better control seizures and reduce the risk of SUDEP.
