S.Sisodiya., M.Thom., J. Liu.
We have carried out a broad range of research studies which have utilised the extensive collections of specimens in the Epilepsy Tissue Bank within the department. This includes studies into mechanisms of drug resistance in epilepsy and the localisation of drug transporter proteins on the vascular endothelium, gene expression studies in epilepsy, the correlation of genome copy variants e.g. 16p13.11 with cortical architectural features and the neuropathology in Dravets syndrome with SCN1A mutations. We have recently explored the patho-mechanisms of white matter abnormalities in focal cortical dysplasia, in terms of myelin abnormalities and oligodendroglial cell maturation. We have correlated patterns of hippocampal sclerosis with outcome following surgery and, utilising post mortem brain samples, how the patter of sclerosis varies through the longitudinal axis of the hippocampus with parallel changes with interneuronal populations. We have also studied patterns of thalamic atrophy in patients with epilepsy and the accumulation of Alzheimer type pathology in relation to lifelong seizures and accumulative traumatic brain injury. We have been carrying out comparative investigations of the patterns of neuronal loss in hippocampal sclerosis in epilepsy and dementia, in relation to sprouting of mossy fibres and alterations of inhibitory interneuronal networks. In studies of SUDEP we have recently audited post mortem practice and investigated patterns of acute neuronal injury in the hippocampus. Ongoing funded studies will address progenitor cell population and gliogenesis in temporal lobe epilepsy and inflammatory pathway activation in SUDEP.
Epilepsy Tissue Bank
(based at UCL, Institute of Neurology)
S.Sisodiya, M Thom, L Martinian
We have continued our research into the neuropathology of epilepsy, focussing on temporal lobe epilepsy associated with hippocampal sclerosis, focal cortical dysplasia and specific pathways, such as cdk5 and its substrates. We showed extensive alteration within this pathway, suggesting links between neurodevelopment and neurodegeneration through disruption of the cell cycle and its regulation, leading, in FCD, to accelerated neuronal loss through tau-mediated processes. We secured funding for research into our valuable post mortem brain archive, which will be studied intensively to explore mechanisms of drug resistance, neuronal loss, gene expression, somatic mutation and recovery from epilepsy.