title: Intrinsic epileptogenicity of dysplastic cortex: converging data from experimental models and human patients.
abstract: Focal cortical dysplasia (FCD) is a brain malformation associated with particularly severe drug-resistant epilepsy that often requires surgery for seizure control. The molecular basis for such enhanced propensity to seizure generation in FCD is not as yet elucidated. To investigate cellular and molecular bases of epileptogenic mechanisms and possible effect of severe epilepsy on the malformed cortex we have here performed a parallel analysis of a rat model of acquired cortical dysplasia previously established in our laboratory, i.e., the methylazoxymethanol/pilocarpine (MAM-PILO) rats, and surgical samples from patients with type IIB FCD. Data from the MAM-PILO rat model and human FCD samples reveal in both conditions: (1) that status epilepticus (SE) and/or seizures can further modify the cellular and molecular settings of the malformed cortex; (2) excitation/inhibition imbalance, and dysregulation of the N-methyl-d-aspartate/ membrane-associated guanylate kinase (NMDA/MAGUK) expression; (3) activation of cell death in neurons and glia. The data therefore highlight the mechanistic relevance of glutamate/NMDA hyperactivation in FCD epileptogenesis and suggest that epilepsy is a pathologic process capable of affecting structure and function of both neurons and glia.
authors.affiliation: Molecular Neuroanatomy and Pathogenesis Unit, IRCCS Foundation Neurological Institute Carlo Besta, Via Libero Temolo 4, Milan, Italy. giorgio.battaglia@istituto-besta.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.forename: Francesca
authors.initials: F
authors.lastname: Colciaghi
authors.forename: Adele
authors.initials: A
authors.lastname: Finardi
authors.forename: Paola
authors.initials: P
authors.lastname: Nobili
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology*; D051528:Guanylate Kinases / Q000378:metabolism*; D006801:Humans; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000503:physiopathology*
chemical_list: D051528:Guanylate Kinases
keywords: Focal cortical dysplasia; Glutamatergic synapse; MAGUK proteins; NMDA receptor; Seizure-induced cell death