MICHAEL PRIZE

Alon Friedman is a neuroscientist at the Ben Gurion University of the Negev. During his medical studies he developed an interest in mechanisms regulating excitability of cortical neurons and epileptogenesis. During his postdoc work he realized that the blood brain barrier can be partially opened under extreme stress conditions. This primed his interest during training as a neurosurgeon and he identified a number of clinical conditions associated with an open blood brain barrier. Using quantitative EEG analysis during his training in G. Wieser’s lab and subsequently he showed that areas with a focally opened blood brain barrier are associated with abnormal EEG activity. He showed in a number of clinical studies that an open blood brain barrier not only increases risk for acute seizures during pharmacological interventions but posed the question whether an open blood brain is in general a risk factor for development of an epileptic focus and development of drug resistance. He chose to open blood brain barrier in a direct approach and established that this will lead to an area of hyperexcitability in the brain which can lead to recurrents, seizures and thus epilepsy. He clarified that the evasion of albumin from the blood vessels into the parenchyma, subsequent regulatory uptake into astrocytes leads to functional alterations in astrocytic properties. By interfering with albumine uptake into astrocytes which is a TGF beta receptor dependent process he was able to prevent subsequent epileptogenesis.

By his expertise as a clinician he has established a comprehensive epilepsy care center in his University hospital which is extremely strong in putting clinical observation into experimentally testable hypotheses. This translational aspect of his work and the discovery that the neurovascular unit is also involved in epileptogenesis is a novel approach for which he is awarded with the Michael Prize 2005/2006.

Dr. Christophe Bernard has devoted himself to translational epilepsy research. He has established an interdisciplinary group aimed at addressing the mechanisms of seizure genesis and propagation in animal models of temporal lobe epilepsy. His main focus is to study the reorganization of the hippocampus CA1 region in epileptic animals to determine the changes that could be considered pro-epileptic vs. those that are compensatory changes and perhaps even antiepileptic in nature. He developed projects to study the dynamics of reorganization during the evolution of epileptogenesis attempting to identify predictive factors that may account for the development of seizures. The research has direct translational applications and can be correlated with studies involving the analysis of stereo-EEG in epileptic patients during the presurgical evaluations. In his award-winning paper, he was able to demonstrate that during the latent period there are specific cell domain/dependent changes in the glutamatergic and GABAergic in the rats CA1 region with a preponderance of global changes to more glutamatergic and less GABAergic activities during the period preceding the chronic development of epilepsy. The data can be used to design specific treatments to prevent the development of epilepsy.

Dr. Bernard's scientific work is in the forefront of translational epilepsy research. The scientific concepts created and further elaborated by Dr. Bernard are indeed evidence of outstanding progress in epileptology and it is expected that they will influence epilepsy research in many years to come.