305 - Temporal Effects of Dose and Fractionation of FLASH and Conventional Irradiation on Hippocampal Neurogenesis and Mechanisms of FLASH-Induced Neuroprotection
Presenter(s)
N. Katila1, S. Melemenidis1, S. Dutt1, L. A. Soto1, D. Chen1, M. R. M. Ashraf1, M. Surucu2, J. Baulch3, O. G. Drayson3, K. P. Jensen4, A. Turcotte1, P. G. Maxim5, L. Skinner1, N. Ru3, P. Loo1, S. J. Yu1, J. B. Schulz1, K. Z. Flores1, E. E. Graves1, C. Limoli3, and B. W. Loo Jr1; 1Department of Radiation Oncology, Stanford University, Palo Alto, CA, 2Department of Radiation Oncology, Stanford University, Stanford, CA, 3University of California, Irvine, Irvine, CA, 4Department of Medicine, Stanford University, Palo Alto, CA, 5Department of Radiation Oncology, University of California - Irvine, Orange, CA
Purpose/Objective(s): Ultra-high dose rate irradiation, known as FLASH, has shown promising potential to spare normal tissues while providing similar antitumor effects compared to conventional dose rate irradiation (CONV). However, the effects of FLASH on brain tissue, specifically on neurogenesis in the hippocampus, have been poorly studied. This study aimed to evaluate the recovery of doublecortin-positive (DCX+) immature neurons in the hippocampus following FLASH and CONV irradiation at early time points (1-, 3-, and 5-weeks post-irradiation) and investigate potential mechanisms related to neuroinflammation and apoptosis.
Materials/Methods: Female C57BL/6J mice (8 weeks old) were irradiated with either FLASH or CONV at single doses of 5 Gy or 10 Gy or a standard-of-care fractionated regimen of 30 Gy (10 fractions of 3 Gy). Brain tissues were collected at 1-, 3-, and 5-weeks post-irradiation. Immunofluorescence imaging was performed to stain DCX, a widely used surrogate marker for adult neurogenesis in the hippocampus. Additional experiments to investigate radiation effects on neuroinflammation and cellular apoptosis were performed.
Results: Female C57BL/6J mice (8 weeks old) were irradiated with either FLASH or CONV at single doses of 5 Gy or 10 Gy or a standard-of-care fractionated regimen of 30 Gy (10 fractions of 3 Gy). Brain tissues were collected at 1-, 3-, and 5-weeks post-irradiation. Immunofluorescence imaging was performed to stain DCX, a widely used surrogate marker for adult neurogenesis in the hippocampus. Additional experiments to investigate radiation effects on neuro-inflammation and cellular apoptosis were performed.
Conclusion:
- FLASH irradiation provides significant neuroprotection over CONV by promoting the recovery of DCX+ neurons along with reducing neuroinflammation and apoptosis.
- The optimal time point for assessing neuronal recovery is 3 weeks post-irradiation.
- These findings suggest that FLASH holds potential for minimizing radiation-induced brain damage, offering a promising strategy for safer brain irradiation in clinical settings.