Abstracts

Rationale:
Seizures are common in patients with high-grade gliomas (30-60%) and approximately 15-30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy.
Method:
Therefore, fifteen rats were inoculated with 20000 F98 GB cells in 5 µL of phosphate buffered saline (PBS) (GB group) and four rats with 5 µL of PBS only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with electrodes in ipsi- and contralateral hippocampus and ipsilateral parietal cortex to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization.
Results:
Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation rats were euthanized based on signs of discomfort and pain.
Conclusion:
This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. Similar to human GB, F98 tumors are characterized by rapid progression and brain tissue invasion and presented with a necrotic core and reactive gliosis in adjacent brain parenchyma. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.
Funding:
:Charlotte Bouckaert is supported by a junior researcher (‘Aspirant’) grant from the “Fonds voor Wetenschappelijk Onderzoek” (FWO, grant 1132820N). This work was supported by an unrestricted educational grant from UCB Pharma. Some of the authors are employees at UCB Pharma.