My laboratory’s research focuses on the discovery of novel diagnostics and therapeutics of epilepsy, one of the most common chronic neurological disorders in humans. Using state-of-the art techniques in chemical profiling by mass spectrometry, we are exploring alterations in the metabolome (entire profile of small molecule metabolites) in brain microdialysis fluids and blood samples from patients with drug-resistant epilepsy. Changes in specific metabolites detected during the initial profiling will be further validated as potential diagnostic markers and therapeutic targets for this disease. We are also investigating the role of glutamate, glutamine synthetase and astrocytes in the causation of epilepsy. Patients with drug-resistant mesial temporal lobe epilepsy have remarkably high levels of the excitatory and toxic amino acid glutamate in their brain. Recent studies by us have indicated that the glutamate overflow in mesial temporal lobe epilepsy may be due to a loss of the enzyme glutamine synthetase in astrocytes of the epileptic brain (Eid et al., Lancet 2004; 363: 28-37). An important goal of our research is to define the relationships among the loss of glutamine synthetase, brain glutamate concentrations, epileptic seizures and epilepsy-related brain damage. To this end we are using a variety of techniques such as simultaneous brain microdialysis and video-intracranial EEG monitoring, 13C- and 15N-isotope labeling studies combined with mass spectrometry and immunogold electron microscopy. We are also exploring the molecular-genetic and proteomic mechanism of the glutamine synthetase deficiency using chromatin immunoprecipitation, 2D gel electrophoresis and mass spectrometry on epileptic brain tissue.
Extensive Research Description
- Characterizing the Metabolome of Epileptic Seizures
- Eid, T., Ghosh, A., Wang, Y., Beckstrom, H., Zaveri, H.P., Lee, T.S., Lai, J.C., Malthankar-Phatak, G.H., and de Lanerolle, N.C. (2008). Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain 131,
- Eid T, Lee TS, Thomas MJ, Amiry-Moghaddam M, Bjornsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC (Jan 2005) Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus., Proceedings of
- Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC, Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temp