Abstracts

Rationale: A common presenting feature of glioma is the sudden occurrence of epileptic seizures at adult age. Accumulating evidence suggests that not the tumor itself, but the peritumoral cortex (PTC) is where the epileptic focus originates, suggesting some form of tumor-brain interaction. However, the alterations in network and cellular function leading to seizure activity due to this interaction are still largely unknown.The objective of this project is to study tumor-associated epilepsy (TAE) by constructing a database of brain tumor patients, including low and high grade glioma, brain metastases and meningioma. Human brain samples are taken from diseased or damaged brain areas in the PTC. Brain samples are used for electrophysiological recordings to study single neuron intrinsic properties, firing behavior and network signaling. Samples are subsequently analyzed with RNA sequencing and mass spectrometry. This will lead to a database containing patient data coupled to single neuron electrophysiological properties, RNA profile and proteomics profile. The project is a collaboration of the departments of Neuroscience and Neurosurgery of the Erasmus Medical Centre in Rotterdam. Methods: This study has been approved by the medical ethics committee of the Erasmus Medical Centre, written informed consent is obtained for each patient. Patients are selected based on tumor type. All relevant patient data is anonymized and recorded in the database. Tissue samples are collected fresh during surgery at the operating rooms and taken to the research unit. The sample is divided into three parts: one part for electrophysiology, one for RNA sequencing and one is snap frozen for proteomics. Using whole cell patch clamping, single neurons are recorded, with a focus on pyramidal cells and interneurons in layer 2-3 and 5-6. RNA sequencing and mass spectrometry is performed on neurons isolated from sample slices. The remaining tissue is further used for immunohistological analysis. Results: At the date of abstract submission the database contains tissue samples from 63 patients. The average age is 58.1 [22–84] years. Histopathological diagnosis grade 2-3 glioma is found in 13 patients, 35 tumors are high grade glioma, 9 are metastases and 6 are meningioma. 22 patients have a history of one or more epileptic seizures pre- and/or post-surgery. Electrophysiological recordings have been performed in 38 patients. RNA sequencing was performed on 2 samples. 10 samples have been analyzed with mass spectrometry. Conclusions: Preliminary results from electrophysiological recordings of single neuron activity reveal changes in intrinsic properties (p Funding: This project is funded through an Erasmus MC Fellowship grant.