Molecular Neuroanatomy and Pathogenesis Unit, IRCCS Foundation Neurological Institute “Carlo Besta”, Milano, Italy, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany, Department of Physiology and Neurobiology, University of Connecticut, Storrs CT, USA, INMED, Inserm U901, Université de la Méditerranée, Campus de Luminy, Marseille, France, Department of Neurological Surgery, University of California, San Francisco, CA, USA, Department of Neurological Surgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy
- Mots-clés : epileptogenesis, glutamate receptors, methylazoxymethanol, pilocarpine, in utero irradiation, MAEUK proteins, MCD, animal model
- DOI : 10.1684/epd.2009.0273
- Page(s) : 206-14
- Année de parution : 2009
Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.