title: The extracellular matrix and diffusion barriers in focal cortical dysplasias.
abstract: Focal cortical dysplasias (FCDs) of the brain are recognized as a frequent cause of intractable epilepsy. To contribute to the current understanding of the mechanisms of epileptogenesis in FCD, our study provides evidence that not only cellular alterations and synaptic transmission, but also changed diffusion properties of the extracellular space (ECS), induced by modified extracellular matrix (ECM) composition and astrogliosis, might be involved in the generation or spread of seizures in FCD. The composition of the ECM in FCD and non-malformed cortex (in 163 samples from 62 patients) was analyzed immunohistochemically and correlated with the corresponding ECS diffusion parameter values determined with the real-time iontophoretic method in freshly resected cortex (i.e. the ECS volume fraction and the geometrical factor tortuosity, describing the hindrances to diffusion in the ECS). The ECS in FCD was shown to differ from that in non-malformed cortex, mainly by the increased accumulation of certain ECM molecules (tenascin R, tenascin C, and versican) or by their reduced expression (brevican), and by the presence of an increased number of astrocytic processes. The consequent increase of ECS diffusion barriers observed in both FCD type I and II (and, at the same time, the enlargement of the ECS volume in FCD type II) may alter the diffusion of neuroactive substances through the ECS, which mediates one of the important modes of intercellular communication in the brain - extrasynaptic volume transmission. Thus, the changed ECM composition and altered ECS diffusion properties might represent additional factors contributing to epileptogenicity in FCD.
authors.affiliation: Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 150 06 Prague, Czech Republic. josef.zamecnik@lfmotol.cuni.cz
authors.forename: Josef
authors.initials: J
authors.lastname: Zamecnik
authors.forename: Ales
authors.initials: A
authors.lastname: Homola
authors.forename: Michal
authors.initials: M
authors.lastname: Cicanic
authors.forename: Klara
authors.initials: K
authors.lastname: Kuncova
authors.forename: Petr
authors.initials: P
authors.lastname: Marusic
authors.forename: Pavel
authors.initials: P
authors.lastname: Krsek
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
authors.forename: Lydia
authors.initials: L
authors.lastname: Vargova
mesh_terms: D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D058581:Brevican / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004058:Diffusion; D004827:Epilepsy; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D007478:Iontophoresis / Q000379:methods; D008297:Male; D054220:Malformations of Cortical Development / Q000378:metabolism / Q000473:pathology*; D065703:Malformations of Cortical Development, Group I; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology; D019063:Tenascin / Q000032:analysis; D053675:Versicans / Q000032:analysis; D055815:Young Adult
chemical_list: D058581:Brevican; D019063:Tenascin; D053675:Versicans; C074638:tenascin R