Abstract
BACKGROUND
The occurrence of seizures is the most common comorbidity in malignant brain tumors. Recent advancements in the field of cancer neuroscience indicate that seizures can potentially influence brain tumor progression through intricate neuron-glioma interactions in the peritumoral infiltrated cortex of glioma patients. Therefore, understanding not only the tumor processes but also the neuronal properties in the tumor microenvironment could provide key insights into the relationship between epilepsy and tumor progression. To investigate this, we conducted a study to characterize neuronal alterations in glioma infiltrated neocortex of both patients and a glioma mouse model.
MATERIAL AND METHODS
Infiltrated peritumoral cortex was obtained from both epileptic and non-epileptic patients undergoing brain tumor surgery. Ex vivo brain slices were prepared and single-cell electrophysiology was performed on peritumoral neurons. High grade gliomas were induced into compound LoxP-conditional mice via stereotactic viral injection in combination with serial electro-corticographic activity to monitor epileptogenesis.
RESULTS
Ex vivo recordings from infiltrated human peritumoral cortex revealed electrophysiological and morphological alterations in neocortical neurons of patients experiencing seizures. Using an inducible immunocompetent high-grade glioma mouse model, we tracked the progression of cortical epileptogenesis during tumor infiltration. We observed several spatial and temporal changes in the peritumoral cortex of glioma mice, including progressive glial reaction and gradual neuronal reduction. We also identified intrinsic and network alterations in the cortical neurons of glioma mouse model, consistent with the electrophysiological characteristics of human peritumoral cortex prior to seizure onset.
CONCLUSION
Overall, our study demonstrated dynamic electrophysiological and histological changes in human and mouse peritumoral cortex during the course of tumor progression and epileptogenesis. These findings provide important insights into brain tumor associated seizures and cast light on new therapeutical targets for treatments.