ArticleBrain structure & function2025
Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.
Article in Brain structure & function, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Microenvironmental remodeling in FLASH radiotherapy.Frontiers in cell and developmental biology · 2026Review
- Factors Influencing the Biological Effects of FLASH Irradiation.Antioxidants (Basel, Switzerland) · 2025Review
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9 authors.
Funding
Abstract
Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) provides relative protection against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity ofgranule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. In this study, we explored the sensitivity of hippocampal CA1 and medial prefrontal cortex (mPFC) pyramidal neurons to cranial irradiation and dose-rate modulation using electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase the length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in mPFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3 × 10 Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are relatively more radioresistant irrespective of radiation dose-rate.
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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.