Abstracts

Rationale: Focal cortical dysplasia type IIB with balloon cells is a developmental malformation of the cerebral cortex highly associated with pharmacoresistant epilepsy. As our previous studies have demonstrated that overexpression of the main adenosine metabolizing enzyme adenosine kinase ( ADK) decreases extracellular adenosine level and consequently leads to seizures, and overexpression of ADK has been regarded as a pathological hallmark of temporal lobe epilepsy, we hypothesized that the epileptogenic mechanisms underlying FCD IIB is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in these patients. Methods: Immunnohistochemistry approach was used to examine the expression of ADK and heterogeneous cell populations expressing cell-surface markers for multipotent progenitors (Nestin), immature neurons (β-tubulin 3, TUJ1), immature glia (vimentin), mature neurons (MAP2), astrocytes (glial fibrillary acidic protein; GFAP), and antiapoptotic gene products (Bcl-2) in surgically resected human epileptic cortical specimens from FCD type IIB (n=20), and compared with control cortical tissues (n=6). ADK expression using western blot and enzymatic activity for ADK were assessed in FCD vs. control samples. Results: Marked expression of the ADK was observed in balloon cells within the lesions of FCD type IIB. Balloon cells were found to be immunoreactive to ADK (77%), GFAP (45%), Bcl-2 (52%), vimentin (39%), TUJ1 (38%), Nestin (26%) and MAP2 (12%). Double labeling showed that there were dually immunopositive for ADK/vimentin (81.5%), ADK/Nestin (78.5%), ADK/GFAP (64.9%), ADK/Bcl-2 (+/+:66.6%), ADK/TUJ1 (36.7%) and ADK/MAP2 (0%) respectively in ADK-positive balloon cells.Significant greater ADK expression in FCD type IIB vs. control was demonstrated by western blot and greater enzymatic activity for ADK was demonstrated using an enzyme-coupled bioluminescent assay. Conclusions: These results suggest that balloon cells are heterogeneous cell populations expressing cell-surface markers for multipotent progenitors, immature neurons/glia, or antiapoptotic gene Bcl-2, and balloon cells with different cell-surface markers express different degrees of ADK. The results suggest that ADK may play a role the regulation of proliferation or apoptosis in the balloon cells with immature property, which may be involved in the pathogenesis of cortical dysplasia. Up-regulation of ADK is a common pathologic hallmark of FCD type IIB and that ADK might be a target in the treatment of epilepsy associated with FCD.