| First Author | Tu KJ | Year | 2023 |
| Journal | Radiat Res | Volume | 200 |
| Issue | 6 | Pages | 587-592 |
| PubMed ID | 37990957 | Mgi Jnum | J:375733 |
| Mgi Id | MGI:8267039 | Doi | 10.1667/RADE-23-00126.1 |
| Citation | Tu KJ, et al. (2023) Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma. Radiat Res 200(6):587-592 |
| abstractText | Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0-20 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients. |
