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: Joanna Goc, Joan Y W Liu, Sanjay M Sisodiya, Maria Thom
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 39 Issue 12 Pg. 2151-62 (Jun 2014) ISSN: 1460-9568 [Electronic] France
• PMID: 24666402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Chemical References

• AIF1 protein, human
• Calcium-Binding Proteins
• DNA-Binding Proteins
• Eye Proteins
• Glial Fibrillary Acidic Protein
• Homeodomain Proteins
• Microfilament Proteins
• NES protein, human
• Nestin
• PAX6 Transcription Factor
• PAX6 protein, human
• Paired Box Transcription Factors
• Repressor Proteins
• SOX2 protein, human
• SOXB1 Transcription Factors
• MCM2 protein, human
• Minichromosome Maintenance Complex Component 2

Topics

• Adolescent
• Adult
• Brain (pathology, physiopathology, surgery)
• Calcium-Binding Proteins
• Cicatrix (etiology, pathology, physiopathology)
• DNA-Binding Proteins (metabolism)
• Electrodes, Implanted (adverse effects)
• Epilepsy (pathology, physiopathology, surgery)
• Eye Proteins (metabolism)
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis (etiology, pathology, physiopathology)
• Homeodomain Proteins (metabolism)
• Humans
• Macrophages (pathology, physiology)
• Male
• Microfilament Proteins
• Microglia (pathology, physiology)
• Middle Aged
• Minichromosome Maintenance Complex Component 2 (metabolism)
• Nestin (metabolism)
• Neurophysiological Monitoring (adverse effects, instrumentation)
• PAX6 Transcription Factor
• Paired Box Transcription Factors (metabolism)
• Repressor Proteins (metabolism)
• SOXB1 Transcription Factors (metabolism)
• Time Factors
• Young Adult