The 2009 Michael Prize was awarded to
Department of Pediatric Neurology
at the Medical Faculty
Carl Gustav Carus Technical University,
Dresden, Germany and
Department of Neurology Clinical Science Center,
Prof. Dr. Hrissanthi Ikonomidou
Department of Anatomy & Neurobiology
University of California
Dr. Hrissanthi Ikonomidou obtained her MD/PhD degree in 1986 from the Georg August University Medical School, and completed 3 years of doctoral-research fellowship at the Max Planck Institute for Experimental Medicine in Gottingen, Germany. After completing her research fellowship with Dr. Olney at the Washington University in St. Louis, she pursued her training in Pediatric Neurology first in Germany and thereafter at the University of Washington in St. Louis in 1995. She then returned to Germany initially working at the Humboldt University in Berlin as an Assistant and Associate Professor in the Department of Neurology. 2004 she was appointed Professor and Head of the Department of Pediatric Neurology at the Medical Faculty Carl Gustav Carus Technical University Dresden, Germany.
Dr. Ikonomidou made a breakthrough observation that medications commonly used to treat seizures can induce apoptosis in the developing brain with potential long term detrimental effects. She has demonstrated that GABA agonists, GABA uptake inhibitors and sodium channel blockers can induce apoptosis, and raised several questions as how to best treat seizures early in life. In subsequent studies, she identified that new antiepileptic drugs may have much lesser prominent effects on apoptosis. In addition, she was able to demonstrate that estrogen treatment may ameliorate the degree of apoptosis. This finding may imply that sex hormones may have a modulatory role on brain development in health and disease.
Her current work has expanded these findings in a very systematic fashion. In elegant papers, Dr. Ikonomidou was able to show that sedative and anticonvulsant drugs suppress postnatal neurogenesis in addition to inducing apoptosis; some of these changes may occur in humans. Indeed, she recently identified that prenatal to monotherapy or polytherapy with antiepileptic drugs leads to decreased grey matter density in subcortical brain regions including the basal ganglia, the hypothalamus and parts of the thalamus in human subjects. This work demonstrates for the first time morphological sequelae of prenatal exposure to antiepileptic drugs in the human brain.
The consistent theme of Dr. Ikonomidou’s work is the understanding of the conditions under which brain injury can occur early in life and how to prevent it. Dr. Ikonomidou’s impact to the scientific community has been remarkable. Through her careful constructed work in animals and humans, she has demonstrated the need to identify age specific antiepileptic agents and has also proposed ways on how to prevent injuries that may occur in this age group as a result of various noxious injuries that seem to share common final pathways. In other words, her data show that the various insults may preferentially use a pathway that is functioning early in life, and this common denominator can produce severe deficits that will not occur in other age groups. The impact of her research findings in the care of patients will be increasing as we, as a community, avail ourselves of her data.
Prof. Dr. Ivan Soltesz obtained his PhD degree in Comparative Physiology from the Eotvos University in 1989 in Budapest. During his undergraduate and graduate years, he studied and carried out research on interneuronal microcircuits in the laboratories of Drs Tamas Freund and Peter Somogyi at the Anatomy Institute in Budapest and at the MRC Anatomical Neuropharmacology Unit in Oxford. Subsequently, as a postdoctoral fellow, he worked with Vincenzo Crunelli in London on sleep rhythms in thalamo-cortical circuits, with Martin Deschenes at Laval University in Quebec City on theta-gamma oscillations in vivo, and with Istvan Mody at Stanford University and in Dallas on plasticity of neuronal excitability in the dentate gyrus. He became a faculty at the University of California, Irvine in 1995, and he has stayed at UC Irvine since. He rose to the ranks of full Professor in 2003, and in 2006 he was elected Chair of the Anatomy & Neurobiology department. He also holds joint faculty appointments in the departments of Physiology & Biophysics, and Neurobiology & Behavior.
Dr. Soltesz’s laboratory has been focused on understanding injury-induced long-term plasticity of limbic microcircuits using a combination of cutting edge techniques, including paired patch clamp recordings from identified neurons and immunocytochemistry. It was Dr. Soltesz’s laboratory that first showed that the h-current and the endocannabinoid system are major sources of plasticity in seizures, which then resulted in whole new fields of research into these topics with the active participation of numerous major epilepsy research laboratories. In addition, his experimental work also identified exciting, novel potential future treatment avenues, including the idea to use, paradoxically, acute pro-convulsants as prophylactic epileptogenic agents. Indeed, his work has demonstrated that administration of a cannabinoid receptor antagonist, a pro-convulsant, abolishes both trauma- and febrile seizure-induced long-term hyperexcitability in the hippocampus. The idea to use acute pro-convulsants for the prevention of acquired epilepsy is not only extremely interesting but also very timely, as effective prophylaxis for post-traumatic epilepsy currently does not exist, and numerous clinical trials using anti-convulsant drugs yielded no long-term anti-epileptogenic effects.
Ivan Soltesz is a leading figure in computational neuroscience and has made very important contributions to understanding the electrophysiology and pharmacochemistry of epileptic discharges. In his submitted papers, Dr. Soltesz has developed the theoretical underpinnings to realistically model the epileptic brain by introducing tools including molecular plasticity as well as homeostasis of network excitability through chronic adjustment in synapses as they are altered by use. The models will provide significant insight for future research by alleviating the need of using experimental animals. His work has helped to merge modern computational approaches with epilepsy research applications, opening up a whole new field of investigation in epilepsy to what is likely to be robust further growth and evolution in the future.
Prof. Dr. Hrissanthi Ikonomidou
Prof. Dr. Ivan Soltesz
The prize money of € 15.000 was kindly donated by UCB International. The Michael Prize was presented at the International Epilepsy Congress in Budapest.
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