title: A spatiotemporal study of gliosis in relation to depth electrode tracks in drug-resistant epilepsy.
abstract: Key questions remain regarding the processes governing gliogenesis following central nervous system injury that are critical to understanding both beneficial brain repair mechanisms and any long-term detrimental effects, including increased risk of seizures. We have used cortical injury produced by intracranial electrodes (ICEs) to study the time-course and localization of gliosis and gliogenesis in surgically resected human brain tissue. Seventeen cases with ICE injuries of 4-301 days age were selected. Double-labelled immunolabelling using a proliferative cell marker (MCM2), markers of fate-specific transcriptional factors (PAX6, SOX2), a microglial marker (IBA1) and glial markers (nestin, GFAP) was quantified in three regions: zone 1 (immediate vicinity: 0-350 μm), zone 2 (350-700 μm) and zone 3 (remote ≥2000 μm) in relation to the ICE injury site. Microglial/macrophage cell densities peaked at 28-30 days post-injury (dpi) with a significant decline in proliferating microglia with dpi in all zones. Nestin-expressing cells (NECs) were concentrated in zones 1 and 2, showed the highest regenerative capacity (MCM2 and PAX6 co-expression) and were intimately associated with capillaries within the organizing injury cavity. There was a significant decline in nestin/MCM2 co-expressing cells with dpi in zones 1 and 2. Nestin-positive fibres remained in the chronic scar, and NECs with neuronal morphology were noted in older injuries. GFAP-expressing glia were more evenly distributed between zones, with no significant decline in density or proliferative capacity with dpi. Colocalization between nestin and GFAP in zone 1 glial cells decreased with increasing dpi. In conclusion, NECs at acute injury sites are a proliferative, transient cell population with capacity for maturation into astrocytes with possible neuronal differentiation observed in older injuries.
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Goc
authors.forename: Joan Y W
authors.initials: JY
authors.lastname: Liu
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
authors.forename: Maria
authors.initials: M
authors.lastname: Thom
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002135:Calcium-Binding Proteins; D002921:Cicatrix / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004567:Electrodes, Implanted / Q000009:adverse effects*; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2 / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D064926:Neurophysiological Monitoring / Q000009:adverse effects / Q000295:instrumentation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; C577484:NES protein, human; D064231:Nestin; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2
keywords: cortical injury; epilepsy; gliosis; nestin-expressing cells