Presenter of 1 Presentation
NEUROLOGICAL MECHANISMS OF PROTECTION IN ADULT MICE EXPOSED TO HYPOFRACTIONATED FLASH RADIOTHERAPY
Abstract
Background and Aims
Past work from our group has documented the neurological benefits of single dose and hypofractionated FLASH radiotherapy (FLASH-RT) in tumor free and orthotopic brain tumor bearing mice as compared to conventional dose rate radiotherapy (CONV-RT).
Methods
To provide mechanistic insight into these observations, adult mice subjected to an isodose of 30 Gy (3x10 Gy) FLASH- or CONV-RT were analyzed for changes in long-term potentiation, synaptic integrity, neuroinflammation and cerebral blood flow, functional and molecular endpoints that were then linked to an extensive series of behavioral outcomes.
Results
Data collected over a 6-month follow-up, show that electrophysiological, molecular and imaging assessments confirm marked sparing of neurological complications in FLASH versus CONV irradiated cohorts, data that is likely contributory (if not causal) to the protection of learning and memory as assessed on 5 separate behavioral testing platforms.
Conclusions
Regardless of interpretation, in no instance were any of the diverse functional and molecular outcomes worse after FLASH-RT, were control and FLASH irradiated cohorts were statistically indistinguishable and differed significantly from CONV irradiated cohorts. These data add to the preponderance of evidence pointing to the translational promise of FLASH-RT and add considerable mechanistic insight into neuroprotective effects of ultra-high dose rate treatments.