title: Review: Roles for astrocytes in epilepsy: insights from malformations of cortical development.
abstract: Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood-brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro-inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence.
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kielbinski
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Gzielo
authors.affiliation: Department of Neuroanatomy, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Soltys
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D004827:Epilepsy / Q000150:complications / Q000473:pathology*; D005911:Gliosis; D006801:Humans; D054220:Malformations of Cortical Development / Q000150:complications / Q000235:genetics / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: astrocyte; cortical dysplasia; epilepsy; glial dysfunction; gliosis