Electrophysiological Characterization of Glioma using a Biomimetic Spheroid Model

Gliomas are the most common form of primary cancer in adults. Depending on the glioma subtype, they cause brain tumor-associated epilepsy (BTAE) in 30-90% of patients. Recently, it has been shown that gliomas form synapses with nearby neurons, which they use to drive their growth. Gliomas themselves also express neurotransmitter receptors. We hypothesized that glioma in isolation may also have its own characteristic electrical activity in response to drugs that are known to modulate synaptic activity in neurons. We generated human glioma spheroids (GS) and performed field potential recordings using multielectrode arrays, in the absence and presence of pro-seizure and anti-seizure drugs, followed by a wash-out period. Statistical differences were determined by one-way or two-way ANOVA with Tukey's post hoc test. The mean firing rate (MFR) of the GS increased from baseline with pro-seizure drug exposure (p<0.01) and returned to baseline levels after the wash-out period from both pro-seizure drugs (p<0.01). The anti-seizure drugs did not significantly alter the MFR of the GS from baseline conditions. The results indicate that GS in isolation are electrically active and they respond to neurotransmitter receptor-modulating drugs. Future studies will be performed to further characterize the electrical activity of glioma with respect to synaptic connectivity and network among glioma cells, and between glioma and other types of brain cells, to better understand their role in BTAE.