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Open AccessArticle

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

1
Department of Radiation Oncology, University of California, Irvine, CA 92697, USA
2
Laboratory of Radiation Oncology, Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, 1000 Lausanne, Switzerland
3
Institute of Radiation Physics/CHUV, Lausanne University Hospital, 1000 Lausanne, Switzerland
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(6), 1671; https://doi.org/10.3390/cancers12061671
Received: 12 April 2020 / Revised: 2 June 2020 / Accepted: 18 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue Advances in Experimental Radiotherapy)
Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients’ quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective “FLASH effect” was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin+) and mature (NeuN+) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors. View Full-Text
Keywords: FLASH radiotherapy; juvenile mice; cognitive dysfunction; neurogenesis; medulloblastoma; pediatric brain cancer; updating task; memory consolidation FLASH radiotherapy; juvenile mice; cognitive dysfunction; neurogenesis; medulloblastoma; pediatric brain cancer; updating task; memory consolidation
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Alaghband, Y.; Cheeks, S.N.; Allen, B.D.; Montay-Gruel, P.; Doan, N.-L.; Petit, B.; Jorge, P.G.; Giedzinski, E.; Acharya, M.M.; Vozenin, M.-C.; Limoli, C.L. Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation. Cancers 2020, 12, 1671.

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