Immunohistochemical characterization of the out-of frame splice variants GFAP Δ164/Δexon 6 in focal lesions associated with chronic epilepsy

SummaryGFAP Δ164/Δexon 6 are two out-of frame splice variants of GFAP. The aim of this study was to investigate the distribution of GFAP Δ164/Δexon 6 expressing cells, in focal lesions associated with chronic intractable epilepsy, in light of the increasing interest in the role of specific astrocyte subtypes in epilepsy.Immunocytochemical analysis, using an antibody against Δ164 and Δexon6 (GFAP+1), was performed in surgical specimens of patients with hippocampal sclerosis (HS), focal cortical dysplasia type IIB (FCD), cortical tubers of tuberous sclerosis complex (TSC), glioneuronal and glial tumors. Expression of GFAP+1 was also evaluated in developing and adult human control cortex and hippocampus.GFAP+1 immunoreactivity was undetectable in developing human brain. In control human hippocampus and cortex (from young controls) only occasional GFAP+1 positive cells were observed. In contrast, GFAP+1 immunoreactivity was consistently detected in the glial component of the epileptogenic lesions. Balloon cells in FCD and giant cells in TSC, only rarely express GFAP+1. GFAP+1 co-localized with GFAPα, but not with GFAPδ. Co-localization with aquaporin 4 was observed around blood vessels.GFAP+1 immunoreactivity in epilepsy-associated pathologies reveals a specific subpopulation of astrocytes in regions of astrogliosis. Further studies on GFAP+1positive astrocytes are important to understand whether the expression of this isoform may affect the cytoskeletal integrity and the shape and function of glial cells under pathological conditions. However, while the staining is increased in epilepsy-associated pathologies, GFAP+1 is expressed in a small percentage of astrocytes. Thus, the possible role of this subpopulation of astrocytes in epilepsy is likely minor, compared to astrocytes expressing other GFAP isoforms.