Decreased paired-pulse inhibition following induced cortical gliomas in the rat

Epilepsy is a poorly understood phenomenon of many patients with gliomas, meningiomas, and other brain tumor entities. Epileptic seizures are frequently the first symptoms of gliomas. The responsible functional modifications of neuronal activity by neoplastic cells are unknown. However, an imbalance of excitation and inhibition has been observed in the vicinity of the neoplasia. We have established a model that enables different experiments on identical tissue preparations. Inoculation of EGFP-transfected rat C6 glioma cells led to intracortical growing gliomas histologically resembling human gliobastomas. Gliomas showed as a solid tumor and an infiltrative zone (100–200µM) surrounded by reactive astrocytes. After 7 days and 14 days, respectively, 400µm thick neocortical coronal brain slices were prepared and the brain excitability was tested with extracellular recording techniques using a paired-pulse stimulus protocol as a measure of excitatory and inhibitory drive. Specifically, we found multiple spikes and a significant reduction of inhibition in the surrounding of the tumoral mass 14 days after glioma cell inoculation. Alterations in the GABAA receptor subunit expression might contribute to this effect. To clarify this we will investigate regional expression of GABAA receptor subunits alpha1, alpha2, alpha3, alpha5, and gamma2 immunohistochemically in a future study.