162 Development of Lentivirus-Induced Pediatric Brainstem Glioma Rat Model

INTRODUCTION: Pediatric brainstem glioma is a common tumor with a poor prognosis. To develop a rat brainstem glioma model, we employed lentiviral gene transfer to deliver oncogene and tumor suppressor impacting the RTK/RAS/PI3K and p53 pathways. METHODS: Twenty-four 6-8 week-old Sprague Dawley rats received stereotactic injections of a combination of lentiviral vectors (PDGF-B, HRAS, shRNA-p53) and control virus in the pontine reticular nucleus. Animals were divided into groups as follows: the control group, the group exhibiting symptoms before neurologic deficit development, the group with a prominent neurological deficit, and the endpoint group. To confirm the tumor growth in each group, animals underwent endpoint MRI, H&E, and immunohistochemical analysis. Glutathione assay and protein carbonyl content assay determined the level of oxidative stress in the groups. RESULTS: All animals exhibited clinical symptoms of brainstem tumors within 21-36 days, including circling and gait instability. MRI scans at the endpoint revealed contrast-enhancing lesions in the pontine region. Immunohistochemistry analysis confirmed the absence of H3K27M and IDH mutations. There was a notable disparity in oxidative stress levels among the groups, correlating directly with the severity of tumor presentation. CONCLUSIONS: Our research has established a rat model of high-grade brainstem glioma induced by lentiviral vectors. Evaluation of various oxidative stress parameters validated the disease's advancement. This model shows promising potential as a platform for pediatric brainstem glioma antisense therapy.