Abstract
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. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle 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 recording electrodes 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. 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. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.
Highlights
Glial tumors or gliomas represent 80% of all malignant brain tumors [1,2]
According to the World Health Organization (WHO) classification system, gliomas can be histologically classified as low-grade gliomas (LGG; ±15% of all gliomas) or high-grade gliomas (HGG; ±85% of all gliomas)
Fifteen male F344/IcoCrl rats were inoculated with 20,000 F98 cells in 5 μL phosphate-buffered saline (PBS) in the right entorhinal cortex (GB1–15)
Summary
Glial tumors or gliomas represent 80% of all malignant brain tumors [1,2]. Eighty percent of HGG are grade IV gliomas, termed glioblastoma (GB), representing the most common and malignant brain tumor and carrying a poor prognosis, with medium survival rates of 12–17 months after diagnosis [3,4,5,6,7]. Seizures represent a common symptom in GB and occur in 30–60% of patients with GB [3,8]. Brain tumor-related seizures typically have a focal onset and can be associated with alteration of consciousness and secondary generalization [3]. Up to 30% of patients with GB suffer from drug-resistant epilepsy (DRE), resulting in significant morbidity and negative impact on quality of life [3,9,10,11]
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