A CVD based radiation detector has recently become commercially available from the manufacturer PTW-Freiburg (Germany). This detector has a sensitive volume of 0.004 mm ³ , a nominal sensitivity of 1 nC Gy ⁻¹ and operates at 0 V. Unlike natural diamond based detectors, the CVD diamond detector reports a low dose rate dependence. The dosimetric properties investigated in this work were dose rate, angular dependence and detector sensitivity and linearity. Also, percentage depth dose, off-axis dose profiles and total scatter ratios were measured and compared against equivalent measurements performed with a stereotactic diode. A Monte Carlo simulation was carried out to estimate the CVD small beam correction factors for a 6 MV photon beam. The small beam correction factors were compared with those obtained from stereotactic diode and ionization chambers in the same irradiation conditions The experimental measurements were performed in 6 and 15 MV photon beams with the following square field sizes: 10 × 10, 5 × 5, 4 × 4, 3 × 3, 2 × 2, 1.5 × 1.5, 1 × 1 and 0.5 × 0.5 cm. The CVD detector showed an excellent signal stability (<0.2%) and linearity, negligible dose rate dependence (<0.2%) and lower response angular dependence. The percentage depth dose and off-axis dose profiles measurements were comparable (within 1%) to the measurements performed with ionization chamber and diode in both conventional and small radiotherapy beams. For the 0.5 × 0.5 cm, the measurements performed with the CVD detector showed a partial volume effect for all the dosimetric quantities measured. The Monte Carlo simulation showed that the small beam correction factors were close to unity (within 1.0%) for field sizes ≥1 cm. The synthetic diamond detector had high linearity, low angular and negligible dose rate dependence, and its response was energy independent within 1% for field sizes from 1.0 to 5.0 cm. This work provides new data showing the performance of the CVD detector compared against a high spatial resolution diode. It also presents a comparison of the CVD small beam correction factors with those of diode and ionization chamber for a 6 MV photon beam.

Cranial irradiation remains a standard treatment for malignant and benign brain diseases. Although this procedure helps to lengthen the life expectancy of the patient, the appearance of adverse effects related to radiationinduced injury is inevitable. Radiation somnolence syndrome (RSS) has been described as a delayed effect observed mainly after whole-brain radiotherapy in children. The RSS was first linked to demyelination, but more recently it has been proposed that the inflammatory response plays a primary role in the aforementioned syndrome. To evaluate the feasibility of this hypothesis, we explored previous work about RSS and reviewed published research that included measurements of the inflammatory response in models of brain exposure to ionizing radiation. Pro-inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, interleukin-6 and interleukin-18 as well as other inflammatory markers such as cyclooxygenase-2, prostaglandin E2, glial fibrillary acid protein, intercellular adhesion molecule-1 and nuclear factor-κB appear to be involved in the brain’s response to radiation. However, certain publications have described the somnogenic effects of these cytokines and inflammatory markers. Although the radiation response is a complex phenomenon that involves several molecular and cellular processes, we propose that inflammation may be closely related to the adverse effects of brain irradiation and therefore to the etiology of RSS.

Implementation of ultra-high dose-rate FLASH radiotherapy (FLASH-RT) is rapidly gaining traction as a unique cancer treatment modality able to dramatically minimize normal tissue toxicity while maintaining antitumor efficacy compared with standard-of-care radiotherapy at conventional dose rate (CONV-RT). The resultant improvements in the therapeutic index have sparked intense investigations in pursuit of the underlying mechanisms. As a preamble to clinical translation, we exposed non–tumor-bearing male and female mice to hypofractionated (3 × 10 Gy) whole brain FLASH- and CONV-RT to evaluate differential neurologic responses using a comprehensive panel of functional and molecular outcomes over a 6-month follow-up. In each instance, extensive and rigorous behavioral testing showed FLASH-RT to preserve cognitive indices of learning and memory that corresponded to a similar protection of synaptic plasticity as measured by long-term potentiation (LTP). These beneficial functional outcomes were not found after CONV-RT and were linked to a preservation of synaptic integrity at the molecular (synaptophysin) level and to reductions in neuroinflammation (CD68+ microglia) throughout specific brain regions known to be engaged by our selected cognitive tasks (hippocampus, medial prefrontal cortex). Ultrastructural changes in presynaptic/postsynaptic bouton (Bassoon/Homer-1 puncta) within these same regions of the brain were not found to differ in response to dose rate. With this clinically relevant dosing regimen, we provide a mechanistic blueprint from synapse to cognition detailing how FLASH-RT reduces normal tissue complications in the irradiated brain. Significance: Functional preservation of cognition and LTP after hypofractionated FLASH-RT are linked to a protection of synaptic integrity and a reduction in neuroinflammation over protracted after irradiation times.

This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates. Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s. Radiation-induced change in tissue oxygenation (ΔpO₂) increased linearly with dose and correlated with baseline tissue oxygenation levels in the range of 0 - 30 mmHg. At higher baseline tissue oxygenation levels, such as those observed in muscle and brain, there was no corresponding increase in ΔpO₂. When we modulated dose rate, ΔpO₂ increased steeply up to ∼ 20 Gy/s and plateaued thereafter. The relationship between ΔpO₂ and dose rate showcases the interplay between ROD and reoxygenation. While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.

Some reports have described that a high fructose diet is associated with a deficit of hippocampus-dependent cognitive functions. In this study, we have evaluated the effects of fructose on spatial memory and molecular markers in the hippocampus and prefrontal cortex and analyzed whether those alterations are reversible. Male Wistar rats (n = 60) began their treatment during adolescence. A group was forced to drink a solution of 10% fructose for twelve weeks. Another group was subjected to the same fructose intake schedule, but later fructose was removed, and tap water was provided for four weeks. After treatments, spatial memory was evaluated with Barnes maze. Different neurogenesis, inflammation, astrocyte, and energy homeostasis markers were evaluated with immunofluorescence, ELISA, and Western blot. Changes were analyzed using two-way repeated-measures ANOVA, one-way ANOVA, and Tukeýs posthoc test (p < 0.05). Results showed that after long-term consumption of fructose, there was an impairment of spatial memory. This deficit was concomitant with the abolition of hippocampal neurogenesis and significant increases of IL-1b in the hippocampus and prefrontal cortex. Levels of COX-2 were decreased in the hippocampus. Besides, fructose induced a significant increase in GFAP and a decrease of glutamine synthetase. Likewise, energy homeostasis-associated neuropeptide orexin-A and their receptors (ORX R1 and ORX R2) were significantly increased. The spatial memory deficit, neuroinflammation, and changes in some proteinś expression were permanent one month after the fructose elimination from the diet. These results suggest that fructose induces substantial hippocampal and cortical changes, and those are irreversible after a shift in the diet.

Gap junctional communication is mainly mediated by connexin36 and connexin43 in neurons and astrocytes, respectively. It has been suggested that connexin36 allows electrical coupling between neurons whereas connexin43 participates in several process including release of ATP. It was recently reported that blockage of gap junctional communication mediated by connexin36 can disrupt the sleep architecture of the rat. However, there is no experimental approach about effects of sleep deprivation on connexins expression. Therefore, we examined in adult male Wistar rats whether protein levels of connexin36 and connexin43 change in pons, hypothalamus, and frontal cortex after 24 h of total sleep deprivation and 4 h of sleep recovery. Western blot revealed that total sleep deprivation significantly decreases the levels of connexin36 in the hypothalamus and this decrease maintains after sleep recovery. Meanwhile, connexin43 is not altered by total sleep deprivation but interestingly the sleep recovery period induces an increase of this connexin. These results suggest that electrical coupling between hypothalamic neurons could be altered by sleep deprivation and that sleep recovery drives changes in connexin43 expression probably as a mechanism related to ATP release and energy regulation during sleep.