The effect of selected drugs on the mitigation of myocardial injury caused by gamma radiation.

Radiation damage of healthy tissues represents one of the complications of radiotherapy effectiveness. This study is focused on the screening of potentially effective drugs routinely used in medical practice and involved in the mechanism of radiation injury, namely for radiation-induced production of free radicals in the body. Experiments in rats revealed significant reduction of oxidative stress (malondialdehyde) and inflammatory marker (tumor necrosis factor α) in 10 Gy irradiated groups after administration of atorvastatin and a slight decrease after tadalafil administration, which indicates that one of the possible mechanisms for mitigation of radiation-induced cardiac damage could be the modulation of nitric oxide (NO) in endothelium and phosphodiesterase 5. In addition, miRNAs were analyzed as potential markers and therapeutically effective molecules. Expression of miRNA-21 and miRNA-15b showed the most significant changes after irradiation. Atorvastatin and tadalafil normalized changes of miRNA (miRNA-1, miRNA-15b, miRNA-21) expression levels in irradiated hearts. This screening study concludes that administration of specific drugs could mitigate the negative impact of radiation on the heart, but more detailed experiments oriented to other aspects of drug effectiveness and their exact mechanisms are still needed.

Experimental investigation and histopathological identification of acute thermal damage in skeletal porcine muscle in relation to whole-body SAR, maximum temperature, and CEM43 °C due to RF irradiation in an MR body coil of birdcage type at 123 MHz.

PURPOSE: This study is an investigation of the relationship between several characteristic parameters and acute thermal damage in porcine skeletal muscle. MATERIAL AND METHODS: Fourteen pigs under injection anaesthesia were placed into a magnetic resonance body coil and exposed for different time durations to different specific energy absorption rate (SAR) levels at 123 MHz. Local temperatures were measured using four temperature sensors. Sensors 1-3 were placed in skeletal muscle and one sensor was placed in the rectum. Sensors 1 and 2 were placed in hot-spot areas and sensor 3 was placed at the periphery of the animals. The pigs were exposed to whole-body SAR (SAR-wb) between 2.5 W/kg and 5.2 W/kg for 30 or 60 min. Three animals received no SAR. After each experiment, muscle samples adjacent to the positions of sensors 1-3 were taken for frozen section analysis. Three characteristic parameters were chosen for investigation: SAR-wb, maximum sensor temperature (T-max), and cumulative equivalent minutes at 43 °C (CEM43 °C). RESULTS: Histopathological criteria were established to detect acute thermal tissue damage in frozen sections such as widening of intercellular space between the muscle fibres and loss of glycogen. Clear tissue damage thresholds were found for T-max and CEM43 °C, though not for SAR-wb. For all animals with high thermal exposure, damage was also found for muscle samples adjacent to the peripheral sensor 3. CONCLUSIONS: Both T-max and CEM43, are able to predict thermal damage in porcine muscle. However, CEM43 is the less ambiguous parameter. The reasons for the occurrence of the aforementioned damage at low local temperatures at the animals' periphery remain unclear and further investigations are needed.

Caffeine eye drops protect against UV-B cataract.

The purpose of this study was to investigate if topically applied caffeine protects against in vivo ultraviolet radiation cataract and if so, to estimate the protection factor. Three experiments were carried out. First, two groups of Sprague-Dawley rats were pre-treated with a single application of either placebo or caffeine eye drops in both eyes. All animals were then unilaterally exposed in vivo to 8 kJ/m(2) UV-B radiation for 15 min. One week later, the lens GSH levels were measured and the degree of cataract was quantified by measurement of in vitro lens light scattering. In the second experiment, placebo and caffeine pre-treated rats were divided in five UV-B radiation dose groups, receiving 0.0, 2.6, 3.7, 4.5 or 5.2 kJ/m(2) UV-B radiation in one eye. Lens light scattering was determined after one week. In the third experiment, placebo and caffeine pre-treated rats were UV-B-exposed and the presence of activated caspase-3 was visualized by immunohistochemistry. There was significantly less UV-B radiation cataract in the caffeine group than in the placebo group (95% confidence interval for mean difference in lens light scattering between the groups = 0.10 ± 0.05 tEDC), and the protection factor for caffeine was 1.23. There was no difference in GSH levels between the placebo- and the caffeine group. There was more caspase-3 staining in UV-B-exposed lenses from the placebo group than in UV-B-exposed lenses from the caffeine group. Topically applied caffeine protects against ultraviolet radiation cataract, reducing lens sensitivity 1.23 times.

The correlation between extracellular resistance by electrical biopsy and the ratio of optical low staining area in irradiated intestinal tissues of rats.

BACKGROUND: Electrical biopsy illustrates a tissue's electrical properties by electrical impedance spectroscopy. However, electrical biopsy parameters are different from conventional morphological-based examinations. The correlation between electrical biopsy and the morphological observation has not been checked. Considering the tissue responses to injury, extracellular resistance should be most sensitive with the accumulation of fluid in tissue, and it is expected to increase the ratio of optical low staining area on histological images. In this study, we calculated the ratio of optical low staining area of sampled histological images and compared with the results of electrical biopsy to verify the hypothesis of that the extracellular resistance of electrical biopsy most highly correlates with the ratio of optical low staining area on histological images. METHODS: The irradiated intestinal tissues of rats after different latent period were used for study. The sampled tissues were measured by electrical impedance spectroscopy for electrical biopsy and the microscopic images were acquired. The sampled histological images were transformed into the Hue-Saturation-Density (HSD) colour model to decouple the stain density. The ratio of optical low staining area on histological images was computed to quantify the morphological changes. The results were related to the parameters from electrical biopsy according to three element circuit model by Spearman's rank correlation test. RESULTS: The ratio of optical low staining area varied as well as the tissue's electrical parameters. The extracellular resistance (Re) and intracellular resistance (Ri) by electrical biopsy tended to increase with the ratio of low staining area decreasing. The membrane capacitance (Cm) by electrical biopsy tended to increase with the ratio of optical low staining area increasing. The extracellular resistance (Re) of electrical biopsy was the parameter most highly correlated with the ratio of optical low staining area with a correlation coefficient of -0.757 (p < 0.001). CONCLUSIONS: The results of this report confirm the hypothesis and support the idea that electrical biopsy results reflect the changes in tissues seen in conventional histological findings in a sense of conventional histological knowledge, and this approach may have a great potential for augmenting the pathological diagnosis of tissues.

Effect of high-intensity irradiation from dental photopolymerization on the isolated and superfused vertebrate retina.

BACKGROUND: Light or electromagnetic radiation may damage the neurosensory retina during irradiation of photopolymerizing resinous materials. Direct and indirect effects of irradiation emitted from polymerisation curing light may represent a severe risk factor for the eyes and the skin of the lamp operators, as well as for the patient's oral mucosa. METHODS: Bovine superfused retinas were used to record their light-evoked electroretinogram (ERG) as ex vivo ERGs. Both the a- and the b-waves were used as indicators for retinal damage on the functional level. The isolated retinas were routinely superfused with a standard nutrient solution under normoglycemic conditions (5 mM D-glucose). The change in the a- and b-wave amplitude and implicit time, caused by low and high intensity irradiation, was calculated and followed over time. RESULTS: From the results, it can be deduced that the irradiation from LED high-power lamps affects severely the normal physiological function of the bovine retina. Irradiations of 1,200 lx irreversibly damaged the physiological response. In part, this may be reversible at lower intensities, but curing without using the appropriate filter will bleach the retinal rhodopsin to a large extent within 20 to 40 s of standard application times. CONCLUSION: Constant exposure to intense ambient irradiation affects phototransduction (a-wave) as well as transretinal signalling. The proper use of the UV- and blue-light filtering device is highly recommended, and may prevent acute and long lasting damage of the neurosensory retina.

Proteins and liver function changes in rats following cumulative total body irradiations.

OBJECTIVE: Total body irradiation (TBI) is a choice therapy for the management of some malignancies; it is also a major cause of oxidative stress. The aim of this research is to sequentially document the effect of total body radiation on body function utilizing the sequential changes in liver function enzymes and proteins in rats. METHODS: Serum protein and liver enzymes were assessed using kits in rats exposed to total body radiations of 1.27 Gy/minute in cumulative doses to the fourth radiation at five-day intervals. RESULTS: Aspartate aminotransferase (AST), alanine transaminase (ALT) and serum protein were significantly (p < 0.05) elevated with increasing radiation. No significant differences between experimental and control groups for bilirubin concentrations were noted at any time. Serum levels of albumin were significantly (p < 0.05) increased with the first to third radiation exposures but reduced at the fourth cumulative dose exposure. CONCLUSION: Variations are associated with acute stress, inflammation which could be due to nonspecific stress reaction, while fluctuations could arise as a result of tolerance and repair within the liver These tests are significant for diagnosis of radiation-induced injury and can be important for evaluation of its severity and correct management.

An indispensable tool: Exosomes play a role in therapy for radiation damage.

Radiotherapy is one of the three main treatments for tumors. Almost 70% of tumor patients undergo radiotherapy at different periods. Although radiotherapy can enhance the local control rate of tumors and patients' quality of life, normal tissues often show radiation damage following radiotherapy. In recent years, several studies have shown that exosomes could be biomarkers for diseases and be involved in the treatment of radiation damage. Exosomes are nanoscale vesicles containing complex miRNAs and proteins. They can regulate the inflammatory response, enhance the regeneration effect of damaged tissue, and promote the repair of damaged tissues and cells, extending their survival time. In addition, their functions are achieved by paracrine signaling. In this review, we discuss the potential of exosomes as biomarkers and introduce the impact of exosomes on radiation damage in different organs and the hematopoietic system in detail.

A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance.

PURPOSE: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. EXPERIMENTAL DESIGN: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. RESULTS: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. CONCLUSIONS: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.

The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage.

PURPOSE: We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS: Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS: RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS: We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.

Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.

Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.

PURPOSE: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. EXPERIMENTAL DESIGN: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT. RESULTS: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens. CONCLUSIONS: The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT.See related commentary by Huang and Mendonca, p. 662.

Ablation of subretinal tissue with optical fiber delivered 266 nm laser pulses.

New and more precise subretinal surgical techniques would be useful in a range of retinal diseases. The purpose of this study is to determine the feasibility of using fiberoptically delivered ultraviolet laser energy to transect or ablate subretinal tissues. Choroid segments dissected from fresh porcine eyes, with or without the retinal pigment epithelium (RPE), were clamped in a fluid bath. Pulsed fourth harmonic (266 nm) of a Nd:YAG laser radiation was delivered via an optical fiber probe at fluence levels between 0.08 and 0.40 J/cm(2). The tissue was then fixed and sectioned for histological examination. Radiation induced damage was categorized by the degree of tissue disruption and ablation depth. Tissue ablation and the severity of the tissue injury varied with both tissue properties and applied laser parameters. Disruption of Bruch's membrane was typically induced by 10 pulses of 0.30 J/cm(2) or 2 pulses of 0.40 J/cm(2). Lower radiation doses did not disrupt Bruch's membrane, but did damage the choroidal tissue and produce vacuoles in the underlying choroid. The full thickness of the choroid was ablated by 200 pulses of 0.40 J/cm(2). The presence of the RPE produced a shielding effect which was greater than would be expected for an equivalent thickness of choroidal tissue. Ablation characteristics of subretinal tissue are highly dependent on the laser parameters used and the type of tissue involved. To perform well controlled laser surgery on subretinal tissues both laser parameters and the properties of the target cells and tissues have to be considered.

Evaluation of Plasma Biomarker Utility for the Gastrointestinal Acute Radiation Syndrome in Non-human Primates after Partial Body Irradiation with Minimal Bone Marrow Sparing through Correlation with Tissue and Histological Analyses.

Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography-tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.

Proteomics of Non-human Primate Plasma after Partial-body Radiation with Minimal Bone Marrow Sparing.

High-dose radiation exposure results in organ-specific sequelae that occurs in a time- and dose-dependent manner. The partial body irradiation with minimal bone marrow sparing model was developed to mimic intentional or accidental radiation exposures in humans where bone marrow sparing is likely and permits the concurrent analysis of coincident short- and long-term damage to organ systems. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the plasma proteome of non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing with 6 MV LINAC-derived photons at 0.80 Gy min over a time period of 3 wk. The plasma proteome was analyzed by liquid chromatography-tandem mass spectrometry. A number of trends were identified in the proteomic data including pronounced protein changes as well as protein changes that were consistently upregulated or downregulated at all time points and dose levels interrogated. Pathway and gene ontology analysis were performed; bioinformatic analysis revealed significant pathway and biological process perturbations post high-dose irradiation and shed light on underlying mechanisms of radiation damage. Additionally, proteins were identified that had the greatest potential to serve as biomarkers for radiation exposure.

Proteomic Evaluation of the Natural History of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Non-human Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing Includes Dysregulation of the Retinoid Pathway.

Exposure to ionizing radiation results in injuries of the hematopoietic, gastrointestinal, and respiratory systems, which are the leading causes responsible for morbidity and mortality. Gastrointestinal injury occurs as an acute radiation syndrome. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the proteome of jejunum from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Jejunum was analyzed by liquid chromatography-tandem mass spectrometry, and pathway and gene ontology analysis were performed. A total of 3,245 unique proteins were quantified out of more than 3,700 proteins identified in this study. Also a total of 289 proteins of the quantified proteins showed significant and consistent responses across at least three time points post-irradiation, of which 263 proteins showed strong upregulations while 26 proteins showed downregulations. Bioinformatic analysis suggests significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. Canonical pathways altered by radiation included GP6 signaling pathway, acute phase response signaling, LXR/RXR activation, and intrinsic prothrombin activation pathway. Additionally, we observed dysregulation of proteins of the retinoid pathway and retinoic acid, an active metabolite of vitamin A, as quantified by liquid chromatography-tandem mass spectrometry. Correlation of changes in protein abundance with a well-characterized histological endpoint, corrected crypt number, was used to evaluate biomarker potential. These data further define the natural history of the gastrointestinal acute radiation syndrome in a non-human primate model of partial body irradiation with minimal bone marrow sparing.

Pilot study of neurologic toxicity in mice after proton minibeam therapy.

Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.

miRNA Expression Patterns Differ by Total- or Partial-Body Radiation Exposure in Baboons.

In a radiation exposure event, a likely scenario may include either total-body irradiation (TBI) or different partial-body irradiation (PBI) patterns. Knowledge of the exposure pattern is expected to improve prediction of clinical outcome. We examined miRNA species in 17 irradiated baboons receiving an upper-body, left hemibody or total-body irradiation of 2.5 or 5 Gy. Blood samples were taken before irradiation and at 1, 2, 7, 28 and 75-106 days after irradiation. Using a qRT-PCR platform for simultaneous detection of 667 miRNAs, we identified 55 miRNAs over all time points. Candidate miRNAs, such as miR-17, miR-128 or miR-15b, significantly discriminated TBI from different PBI exposure patterns, and 5-to-10-fold changes in gene expression were observed among the groups. A total of 22 miRNAs (including miR-17) revealed significant linear associations of gene expression changes with the percentage of the exposed body area (P < 0.0001). All these changes were primarily observed at day 7 postirradiation and almost no miRNAs were detected either before or after 7 days. A significant association in the reduction of lymphocyte counts in TBI compared to PBI animals corresponded with the number of miRNA candidates. This finding suggests that our target miRNAs predominantly originated from irradiated lymphocytes. In summary, gene expression changes in the peripheral blood provided indications of the exposure pattern and a suggestion of the percentage of the exposed body area.

[Peculiar effects of low doses of high let radiation on mice].

Experiments with exposure of mice to low doses of chronic high-LET radiation were carried out in the radiation field behind the concrete wall of the Serpukhov accelerators of protons with the energy of 70 GeV. The goal was to study dose dependence, radiation adaptive response (AR), and genetic instability. Mice (SHK strain) were irradiated continuously 15, 24 and 31 days which corresponded to the doses of 11.5, 21.5 and 31.5 Gy. Cytogenetic damages were determined using the micronuclear test in marrow polychromatophil erythrocytes. It was shown that all the experimental doses aggravated the cytogenetic damage; however, no AR induction in marrow cells was observed. Males of the F1 generation born from the males irradiated at 11.5 Gy had same level of spontaneous cytogenetic damage as males born from non-irradiated parents. Yet, they displayed an exaggerated sensitivity to additional exposure to 1.5 Gy and no AR induction by the standard gamma-protocol which is indicative of genetic instability.

Removal of the blue component of light significantly decreases retinal damage after high intensity exposure.

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400-500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated.

Focal brain lesions induced with ultraviolet irradiation.

Lesion and inactivation methods have played important roles in neuroscience studies. However, traditional techniques for creating a brain lesion are highly invasive, and control of lesion size and shape using these techniques is not easy. Here, we developed a novel method for creating a lesion on the cortical surface via 365 nm ultraviolet (UV) irradiation without breaking the dura mater. We demonstrated that 2.0 mWh UV irradiation, but not the same amount of non-UV light irradiation, induced an inverted bell-shaped lesion with neuronal loss and accumulation of glial cells. Moreover, the volume of the UV irradiation-induced lesion depended on the UV light exposure amount. We further succeeded in visualizing the lesioned site in a living animal using magnetic resonance imaging (MRI). Importantly, we also observed using an optical imaging technique that the spread of neural activation evoked by adjacent cortical stimulation disappeared only at the UV-irradiated site. In summary, UV irradiation can induce a focal brain lesion with a stable shape and size in a less invasive manner than traditional lesioning methods. This method is applicable to not only neuroscientific lesion experiments but also studies of the focal brain injury recovery process.