Scientific Title: Thalamic GABA in childhood and juvenile absence epilepsy
Lead investigator: Professor Vincenzo Crunelli, Cardiff University
Co-investigators: Prof Richard Wise, Cardiff University, Dr Khalid Hamandi, Cardiff and Vale University Health Board, Dr Daniella Brazzo, Cardiff and Vale University Health Board
Pilot grant: £30,000, 2 years
“We are excited by the possibility of testing our hypothesis with state of the art MRI scans in a young population with absence seizures. This data will in the medium-term inform the development of novel drugs that selectively target the aberrant mechanisms responsible for increased GABA levels in sub- populations of people with absences, and potentially control both their seizures and the associated cognitive deficits.” Professor Vincenzo Crunelli, Cardiff University
Neurons can increase or decrease the activity of other neurons by releasing chemicals, called neurotransmitters, thus producing excitation or inhibition, respectively, of their neighbours. The normal function of the brain relies on an intricate balance between excitation and inhibition within and across different brain regions. Decreased inhibition and/or increased excitation are currently believed to underlie the generation of epileptic seizures. However, there are different types of inhibition in the brain. The researchers discovered that there is an elevated activity of the inhibitory neurotransmitter GABA in a brain region called the thalamus in different animal models of absence seizures. Absence seizures are epileptic seizures that are particularly common in children and teenagers. In animal models of absences, elevated GABA activity is both necessary and sufficient for the generation of absence seizures, and a higher GABA concentration was recently reported in one child showing abnormal electrical activity seen in absence seizures.
This study will use a high strength brain scanner (only available in a few places worldwide) to compare the concentration of GABA in the thalamus and cortex between normal children and teenagers, with those with absence seizures.
These results will provide the necessary preliminary data for a larger study aimed at investigating whether abnormal GABA levels in different brain regions of young people with absence seizures are a consistent feature of these seizures and whether it can predict the response to anti-epileptic medications. The results may help direct the development of new therapies.