Glial regenerative cell types in the superficial cortex in cortical dysplasia subtypes

Liu, J., Reeves, C., van der Pijl, R. and Thom, M. 2021. Glial regenerative cell types in the superficial cortex in cortical dysplasia subtypes. Epilepsy Research. 169 106529. https://doi.org/10.1016/j.eplepsyres.2020.106529

TitleGlial regenerative cell types in the superficial cortex in cortical dysplasia subtypes
TypeJournal article
AuthorsLiu, J., Reeves, C., van der Pijl, R. and Thom, M.
Abstract

Purpose: Focal Cortical Dysplasias (FCD) are localized malformative brain lesions in epilepsy. FCD3a associated with hippocampal sclerosis, affects the superficial cortex and is presumed to have an ‘acquired’ rather than developmental origin. Precursor cells may arise outside neurogenic zones including cortical layer I. Our aim was to characterise subsets of glial progenitor cells in the superficial cortical layers, known to be involved in gliosis and gliogenesis and that could distinguish FCD3a from other subtypes.

Methods: Using immunohistochemistry we quantified the density of glial progenitor subsets in superficial cortex layers using markers against PAX6, GFAP, Olig2 and PDGFRβ and proliferation marker MCM2 in ten FCD3a cases compared to 18 other FCD types and 11 non-FCD controls.

Key Findings: Glial progenitor cells types were present in the cortical layer I and II in all FCD groups. GFAP cells frequently expressed PAX6 and significantly higher GFAP/PAX6 than GFAP/MCM2 cell densities were identified in the FCD3a group (p<0.05). Olig2 cell densities were significantly higher in FCD3b than FCD3a (p=0.002) and significantly higher GFAP/MCM2 compared to PDGFRβ/MCM2 cell densities were identified in both FCD3b and FCD2 groups. There was no correlation between cell densities and the age of patients at surgery and between cortical regions.

Significance: Immature and proliferative glial populations across FCD variants reflect ‘reactive cell types and differences may provide insight into underlying pathomechanisms. Higher PAX6 expression in astroglial cells in FCD3a may indicate a switch to astrocytic maturation and enhanced superficial gliosis. Higher Olig2 and GFAP/MCM2 densities in FCD3b may reflect margins of the tumour infiltration zone rather than true cortical dysplasia.

KeywordsCortical layer I II
glial regeneration
cortical dysplasia
Article number106529
JournalEpilepsy Research
Journal citation169
ISSN0920-1211
Year2021
PublisherElsevier
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1016/j.eplepsyres.2020.106529
Publication dates
Published online10 Dec 2020
Published in printJan 2021
FunderMedical Research Council

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