Nihal DeLanerolle, DPhil, DSc

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.

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

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.