ArticleNeuro-oncology2023
Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Neurocognitive outcomes in patients with brain metastases: a systematic review.The Lancet. Oncology · 2025Pooled it
- Impact assessment of current knowledge gaps and mitigation strategies in clinical FLASH proton therapy through a systematic review.Frontiers in oncology · 2025Pooled it
- Electron FLASH radiotherapy in vivo studies. A systematic review.Frontiers in oncology · 2024Pooled it
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- The Sparing Effect of Multibeam Ultra-High Dose-Rate Irradiation on Intestinal Tissue in Mice.Cancer science · 2026Article
- Early microglial activation in the TME enables FLASH-RT to eradicate medulloblastoma while promoting neuron-astrocyte crosstalk to minimize toxicity in the hippocampus.bioRxiv : the preprint server for biology · 2026Article
- Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.International journal of radiation oncology, biology, physics · 2026Article
- FLASH radiotherapy as an emerging paradigm in radioimmunotherapy: biological rationale, preclinical evidence, and translational roadmap.Frontiers in immunology · 2026Review
- Microenvironmental remodeling in FLASH radiotherapy.Frontiers in cell and developmental biology · 2026Review
- The potential and risks of FLASH radiotherapy in pediatric patients.Neuro-oncology pediatrics · 2026Review
- Systematic analysis of biological endpoint variability and implications for quantitative modeling of the FLASH sparing effect.Physics and imaging in radiation oncology · 2026Review
- Mechanisms, challenges and opportunities for FLASH radiotherapy in cancer.Nature reviews. Cancer · 2026Review
- Factors Influencing the Biological Effects of FLASH Irradiation.Antioxidants (Basel, Switzerland) · 2025Review
- The Biophysics of Flash Radiotherapy: Tools for Measuring Tumor and Normal Tissues Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Ex vivo brain MRI to assess conventional and FLASH brain irradiation effects.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- Preparations for Ultra-High Dose Rate 25-90 MeV Electron Radiation Experiments with a Compact, High-Peak-Current, X-band Linear Accelerator.Radiation research · 2025Article
- Pediatric CNS Radiation Oncology: Recent Developments and Novel Techniques.Current oncology (Toronto, Ont.) · 2025Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundUltrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes.
methodsCohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment. Animals were sacrificed 6 months post-irradiation and tissues were analyzed for neurological and cerebrovascular decrements.
resultsThe neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neurocognitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin), and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and the preservation of the cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels.
conclusionsHypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlights its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefits of FLASH-RT that extend from synapse to cognition and the microvasculature.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.