• Epilepsy research · Apr 2007

    Inhibitory networks in epilepsy-associated gangliogliomas and in the perilesional epileptic cortex.

    • E Aronica, S Redeker, K Boer, W G M Spliet, P C van Rijen, J A Gorter, and D Troost.
    • Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. e.aronica@amc.uva.nl
    • Epilepsy Res. 2007 Apr 1; 74 (1): 33-44.

    AbstractDevelopmental glioneuronal lesions, such as gangliogliomas (GG) are increasingly recognized causes of chronic pharmaco-resistant epilepsy. It has been postulated that chronic epilepsy in patients with malformations of cortical development is associated with dysfunction of the inhibitory GABA-ergic system. We aimed to identify the subtypes of interneurons present within GG specimens and the expression and cellular distribution patterns of GABA receptors (GABAR) and GABA transporter 1 (GAT1). The expression of the various components of the GABA-ergic system were also analyzed in the perilesional cortex. We investigated the expression of parvalbumin, calbindin, calretinin, GABA(A)R (a1 subunit)(,) GABA(B) (R1 and R2) and GAT-1 using immunocytochemistry in 30 specimens of GG obtained during epilepsy surgery, including 10 cases with sufficient amount of perilesional cortex. Immunocytochemistry for calbindin (CB), calretinin (CR) and parvalbumin (PV) demonstrate the presence of inhibitory neurons of different subtypes within the GG specimens. Calcium-binding protein-positive interneurons represent a small fraction of the total neuronal population. Both GABA(A)R and GABA(B)R (R1 and R2) subtypes were detected within the neuronal component of GG specimens. In addition, GABA(B)R2 immunoreactivity (IR) was observed in glial cells. GG specimens displayed also expression of GAT-1 IR. Compared to normal cortex, the density of PV- and CB-immunoreactive interneurons was reduced in the perilesional cortex of GG patients, whereas CR-labeling was similar to that observed in normal cortex. GAT-1 IR was also significantly reduced in the perilesional specimens. The cellular distribution of components of the GABA-ergic system in GG, together with the perilesional changes suggest that alterations of the GABA-ergic system may contribute to the complex abnormal functional network of these highly epileptogenic developmental lesions.

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