Visual and Quantitative Electroencephalographic Effects of mTOR Inhibitor AZD8055 in a Diffusely Infiltrating Glioma Mouse Model
Abstract number :
3.261
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2021
Submission ID :
1826428
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Andrew Michalak, MD - Columbia University Irving Medical Center - New York Presbyterian Hospital; Alexander Goldberg, MS - MD/PhD Student, Neurobiology and Behavior, Columbia University; Athanassios Dovas, PhD - Associate Research Scientist, Department of Pathology and Cell Biology, Columbia University Irving Medical Center - New York Presbyterian Hospital; Wayne Frankel, PhD - Professor, Institute for Genomic Medicine, Columbia University Irving Medical Center - New York Presbyterian Hospital; Peter Canoll, MD, PhD - Professor, Department of Pathology and Cell Biology, Columbia University Irving Medical Center - New York Presbyterian Hospital; Catherine Schevon, MD, PhD - Associate Professor, Neurology, Columbia University Irving Medical Center - New York Presbyterian Hospital
Rationale: Greater than 80% of glioma patients suffer from seizures. First trials of anti-epileptic drugs resolve seizures in 23% of patients, compared to nearly 50% of patients with general epilepsy.1 Aberrant neuronal activity has recently been proposed to contribute to increased glioma growth and proliferation. Although mTOR inhibitors have shown reliable results in epilepsy related to tuberous sclerosis complex (TSC), less is known about their role in non-TSC epilepsy. Furthermore, AZD8055, a competitive dual mTORC1/2 inhibitor, has been shown to have anti-tumor effects in mouse models glioblastoma.2 Here we describe the anti-seizure and quantitative effects of AZD8055 on a mouse model of diffusely infiltrating glioma.
Methods: Glioma cells were generated as previously described3, and were injected into subcortical white matter of C57BL/6 mice. Within one week after tumor cell injection, mice underwent electrode implantation. 5 tumor-bearing mice and one tumor-negative control mouse were connected to scalp electroencephalogram (EEG) and periodically monitored for 48-hour video EEG recording sessions between days 6-45 post-injection (DPI). 2 mice were given AZD8055 100mg/kg via oral gavage at DPI 14, and 3 mice were given 20mg/kg at 21 DPI followed by 100mg/kg at 39 DPI. Visual inspection of the EEG, as well as quantitative linelength analysis using custom MATLAB scripts was performed.
Results: Two of the five tumor bearing mice developed seizures and an additional mouse developed discharges but no seizures. After administration of a single 100 mg/kg dose of AZD8055 there was attenuation of the background, and no seizures or discharges were seen (Figure 1). The average linelength across all five animals was significantly reduced (p < .05, two-tailed student’s t-test) as early as 6 hours after treatment when compared to the pre-AZD linelength (Figure 2).
Anti-seizure Medications