Epilepsy; Nervous System; Trauma, Nervous System
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.
Our studies on traumatic brain research are focused primarily on brain injury caused by explosive blast pressure waves as encountered by soldiers in warfare.
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, cellular and molecular 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. Our studies specially focus on the role of inflammatory processes in epileptogenesis and the maintenance of 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.
In a second line of investigations the laboratory focusses on the neuropathology of the brain in soldiers and large animals exposed to explosive blast pressure waves in order to understand the neural mechanisms underlying neuropsychiatric disorders associated with exposure to blast. Completed studies have found for the first time unequivocal evidence of injury to the anterior hippocampaus correlated with memory impairments, and a unique pattern of periventricular axonal injury. Present work is further exploring the relationship of periventricular injury to suicide and depression.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.
- de Lanerolle, N.C., J.H. Kim, and F.A. Bandak (2015) Neuropathology of traumatic brain injury: Comparison of penetrating, non-penetrating direct impact and explosive blast etiologies. Seminars in Neurol, 35: 12-19
- de Lanerolle, NC., Hamid, H., Kulas, J., Pan, J., Czlapinski, R., Rinaldi, A., Ling, G., Bandak, F. and Hetherington, H. (2014) Concussive brain injury from explosive blast. Annals Clin Transl. Neurol. 1: 692 - 702
- De Lanerolle, N.C. Lee. T-S. and Spencer, D.D. Histopathology of human epilepsy In: Jasper’s Basic Mechanisms of Epilepsies, 4th Edition (Eds) J.L. Noebels, M. Avoli, M.A. Rogawski, and R.W. Olsen. Chapter 30, p. 387 Oxford University Press, 2012
- de Lanerolle, N.C., Lee, T-S. and Spencer, D.D. (2010)Astrocytes and epilepsy. Neurotherapeutics 6: 135-144