Nihal C. DeLanerolle DPhil, D.Sc.

Professor of Neurosurgery and of Neurobiology

Research Interests

Molecular and cellular neuropathology of human seizure foci; Development of animal models of human temporal lobe epilepsy; Neuropathology of Traumatic brain injury

Current Projects

Efficacy of erythropoietin (EPO) and EPO analogues in the treatment of temporal lobe epilepsy.

Neuropathology of blast related traumatic brain injury.

The role of glia in the development of hippocampal seizure foci.

Research Summary

In many types of epilepsy, notably in Temporal Lobe Epilepsy (TLE), seizures originate from regions of the brain that are anatomically and physiologically disorganized (seizure foci). The goal of our research is the analysis of the neuropathology of seizure foci to determine how they generate and maintain seizures. State-of-the-art molecular neuroanatomical techniques are employed to define the neuroanatomical substrates for specific types of epilepsy, while high-throughput gene expression analyses and proteomics are further employed to define the molecular complexity that underlies seizure foci.

Astrocytes in human seizure foci are targeted in studies to define their role in seizure maintenance and epileptogenesis. Our hypothesis is that astrocytes are the source of high extracellular glutamate at seizure foci through their responsiveness to inflammatory factors and modification of the blood-brain barrier at seizure foci. The laboratory is also developing new animal models of epilepsy, based on results of human studies, for translational research.

Extensive Research Description

My laboratory is engaged in a study of the pathophysiology of seizure foci in the brains of patients with epilepsy. Our work has concentrated on the molecular and cellular organization of hippocampal seizure foci in patients with medically intractable temporal lobe epilepsy, who have this seizure focus removed in our epilepsy surgery program for the control of seizures. In the past our work has defined the anatomical and cellular organization of the hippocampal seizure focus in patients with mesial temporal lobe epilepsy.

Our current work focuses on the molecular characterization these seizure foci through the use of high throughput techniques such as DNA microarray analysis and proteomics. The work completed using these techniques has focused attention on the molecular changes in reactive astrocytes at seizure foci, which appear to play a critical role in causing an excitable environment in the brain. Gene expression profiles in the blood of patients with temporal lobe epilepsy are also being carried out with the goal of identifying biomarkers of different subclasses of temporal lobe epilepsy and for predicting, prior to surgery, the outcome of surgery for controlling seizures.

In parallel with studies on human seizure foci, the laboratory is also developing and characterizing new animal models of temporal lobe epilepsy that better reflect the pathophysiological changes in human seizure foci. These translational studies are aimed at developing and testing new antiepileptic drugs and developing methods for seizure prediction.

This year the laboratory was awarded an NIH grant for the study of proteomic profiles in human seizure foci (PI, Nihal de Lanerolle) and for the continued development of a new animal model of seizures (PI, Tore Eid). It also received an award from DARPA for the study of blast induced brain injury.

Selected Publications

  • Eid, T., Ghosh, A., Wang, Y., Beckstrom, H., Zaveri, H., Lee, T-S., Lai, J.K.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 (July 6) doi:10.1093/brain/awn133
  • Lee, T-S., Mane, S., Eid, T., Zhao, H., Lin, A., Guan, Z., Kim, J.H., Schweitzer, J., King-Stevens, D., Weber, P., Spencer, S.S., Spencer, D.D., and de Lanerolle, N.C. (2007) Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol. Med. 13: 1-13
  • Eid, T., Hammer, J., Runden-Pran, E., Roberg, B., Thomas, M.J., Osen, K., Davanger, S., Laake, P., Torgner, I.A., Lee, T-S.W., Kim, J.H., Spencer, D.D., Ottersen, O.P., and de Lanerolle, N.C. (2007) Increased expression of phosphate activated glutaminase in hippocampal neurons in human mesial temporal lobe epilepsy. Acta Neuropathol. 113: 137-152
  • de Lanerolle, N.C. and Lee, T-S. (2005) New facets of the neuropathology and molecular profile of human temporal lobe epilepsy. Epilepsy & Behav. 7:190-203.

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