Effects of proton and oxygen ion irradiation on cardiovascular function and structure in a rabbit model.

PURPOSE: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model. MATERIALS AND METHODS: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions (16O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury. RESULTS: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild. CONCLUSION: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models.

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure.

Space exploration requires the characterization and management or mitigation of a variety of human health risks. Exposure to space radiation is one of the main health concerns because it has the potential to increase the risk of cancer, cardiovascular disease, and both acute and late neurodegeneration. Space radiation-induced decrements to the vascular system may impact the risk for cerebrovascular disease and consequent dementia. These risks may be independent or synergistic with direct damage to central nervous system tissues. The purpose of this work is to review epidemiological and experimental data regarding the impact of low-to-moderate dose ionizing radiation on the central nervous system and the cerebrovascular system. A proposed framework outlines how space radiation-induced effects on the vasculature may increase risk for both cerebrovascular dysfunction and neural and cognitive adverse outcomes. The results of this work suggest that there are multiple processes by which ionizing radiation exposure may impact cerebrovascular function including increases in oxidative stress, neuroinflammation, endothelial cell dysfunction, arterial stiffening, atherosclerosis, and cerebral amyloid angiopathy. Cerebrovascular adverse outcomes may also promote neural and cognitive adverse outcomes. However, there are many gaps in both the human and preclinical evidence base regarding the long-term impact of ionizing radiation exposure on brain health due to heterogeneity in both exposures and outcomes. The unique composition of the space radiation environment makes the translation of the evidence base from terrestrial exposures to space exposures difficult. Additional investigation and understanding of the impact of low-to-moderate doses of ionizing radiation including high (H) atomic number (Z) and energy (E) (HZE) ions on the cerebrovascular system is needed. Furthermore, investigation of how decrements in vascular systems may contribute to development of neurodegenerative diseases in independent or synergistic pathways is important for protecting the long-term health of astronauts.

Angiographic predictors of coronary hemodynamics.

Aims: Assess the correlation between diameter stenosis, lesion length, location, diffuse coronary disease and with fractional flow reserve (FFR). Methods/Results: We performed quantitative coronary analysis analysis on 384 lesions with stable coronary artery disease undergoing FFR assessment. Vessels were 59.1% left anterior descending artery (LAD), 16.1% left circumflex artery and 14.8% right coronary artery. Median diameter stenosis was 58% ± 2.5 and median lesion length was 10 mm ± 7.36. 21% of vessels were diffusely diseased. Lesions were 33.6% proximal, 44% mid-vessel and 12% distal. Median FFR was 0.85. Diameter stenosis correlated with lower FFR (p < 0.005, odds ratio [OR]: 2.4 [95% CI: 0.99-5.63]). There was no association between lesion length, location, number of proximal side branches and FFR. Vessels with diffuse disease had a nonsignificant trend for lower FFR (0.84 vs 0.85, p = 0.375, OR: 1.26 [95% CI: 0.76-2.09]). LAD lesions had significantly lower FFR compared with non-LAD (p < 0.001, OR: 2.55 [95% CI: 1.61-4.04]); including left circumflex artery and right coronary artery lesions (p = 0.001, OR: 3.4 [95% CI: 1.7-6.9]) and p = 0.02, OR: 2.55 [95% CI: 1.17-4.34]). Conclusion: FFR is not related to lesion length, location or number of proximal branches.

The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures.

In the coming decade, astronauts will travel back to the moon in preparation for future Mars missions. Exposure to galactic cosmic radiation (GCR) is a major obstacle for deep space travel. Using multivariate principal components analysis, we found sex-dimorphic responses in mice exposed to accelerated charged particles to simulate GCR (GCRsim); males displayed impaired spatial learning, whereas females did not. Mechanistically, these GCRsim-induced learning impairments corresponded with chronic microglia activation and synaptic alterations in the hippocampus. Temporary microglia depletion shortly after GCRsim exposure mitigated GCRsim-induced deficits measured months after the radiation exposure. Furthermore, blood monocyte levels measured early after GCRsim exposure were predictive of the late learning deficits and microglia activation measured in the male mice. Our findings (i) advance our understanding of charged particle­induced cognitive challenges, (ii) provide evidence for early peripheral biomarkers for identifying late cognitive deficits, and (iii) offer potential therapeutic strategies for mitigating GCR-induced cognitive loss.

Trends in Rural Outreach by Orthopedic Surgeons.

BACKGROUND: Sixty million rural residents have limited access to orthopedic care due to a small rural orthopedic surgery workforce. Increases in specialized training add to the challenge of attracting orthopedic surgeons to rural communities. Answering the call for research on models to meet the needs of rural orthopedic patients, we examine long-term trends in visiting consultant clinics (VCCs) in Iowa, a state with a large rural population. METHODS: The Office of Statewide Clinical Education Programs (Carver College of Medicine) compiles an annual report of outreach clinic locations, frequencies and participating physicians. Trends in the total number of VCCs, days and locations (1989-2018) were analysed using joinpoint analysis. RESULTS: Total clinic days grew rapidly from 1992-1997 (Average Percent Change: 19.7%) before a decline ending in 2009 (APC: -4.1%). A new growth period (2009-2013, APC: 7.5%) preceded another decline (APC: -3.6%) ending in 2018. The number of cities hosting a VCC grew from 56 (1989) to a peak of 90 (1999) and fell an average of 0.9% a year thereafter. More than 80% of all VCCs in the last ten years were offered 2 or more times per month. The average participation rate for Iowa-based orthopedic surgeons was 44%. The mean number of VCCs staffed by a single physician was 1.32 (std. dev. = 0.53) with a median of 1. The average number of VCC days per month for a participating physician was 3.22 (std. dev. = 2.41) with a median of 2.66. CONCLUSION: The VCC model of rural outreach is sustainable (30+ year history) and self-funded. Most clinics occur with sufficient frequency to allow timely follow-up care. This model of rural outreach is supported by the participation of a large segment (44%) of Iowa's orthopedic surgeons. Visiting orthopedic surgeons provide access to care in 65 of the 76 Critical Access Hospitals in Iowa offering orthopedic services compared to 8 staffed by a local orthopedic surgeon.Level of Evidence: V.

Evaluating Ocular Response in the Retina and Optic Nerve Head after Single and Fractionated High-Energy Protons.

There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and blood-retina barrier (BRB) integrity in the retina and optic nerve head (ONH) region and to compare these radiation-induced effects with those produced by fractionated dose. Six-month-old C57BL/6 male mice were either sham irradiated or received whole-body high energy proton irradiation at an acute single dose of 0.5 Gy or 12 equal dose fractions for a total dose of 0.5 Gy over twenty-five days. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. Significant increases in the number of apoptotic cells were documented in the mouse retinas and ONHs that received proton radiation with a single or fractionated dose (p < 0.05). Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina and ONH following single or fractionated protons with more pronounced changes observed with a single dose of 0.5 Gy. BRB integrity was also evaluated with biomarkers of aquaporin-4 (AQP-4), a water channel protein, a tight junction (TJ) protein, Zonula occludens-1 (ZO-1), and an adhesion molecule, the platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following a single dose exposure compared to controls. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina. These changes give a strong indication of disturbance to BRB integrity in the retina. Interestingly, there was very limited immunoreactivity of AQP-4 and ZO-1 seen in the ONH region, pointing to possible lack of BRB properties as previously reported. Our data demonstrated that exposure to proton radiation of 0.5 Gy induced oxidative stress-associated apoptosis in the retina and ONH, and changes in BRB integrity in the retina. Our study also revealed the differences in BRB biomarker distribution between these two regions. In response to radiation insults, the cellular response in the retina and ONH may be differentially regulated in acute or hyperfractionated dose schedules.

Multiple sensory illusions are evoked during the course of proton therapy.

Visual illusions from astronauts in space have been reported to be associated with the passage of high energy charged particles through visual structures (retina, optic nerve, brain). Similar effects have also been reported by patients under proton and heavy ion therapies. This prompted us to investigate whether protons at the Loma Linda University Proton Therapy and Research Center (PTRC) may also affect other sensory systems beside evoking similar perceptions on the visual system. A retrospective review of proton radiotherapy patient records at PTRC identified 29 sensory reports from 19 patients who spontaneously reported visual, olfactory, auditory and gustatory illusions during treatment. Our results suggest that protons can evoke neuronal responses sufficient to elicit conscious sensory illusion experiences, in four senses (auditory, taste, smell, and visual) analogous to those from normal sensory inputs. The regions of the brain receiving the highest doses corresponded with the anatomical structures associated with each type of illusion. Our findings suggest that more detailed queries about sensory illusions during proton therapy are warranted, possibly integrated with quantitative effect descriptions (such as electroencephalography) and can provide additional physiological basis for understanding the effects of protons on central nervous system tissues, needed for radiation risk assessment in advance of deep space human exploration.

Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats.

PURPOSE: Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model. MATERIALS AND METHODS: In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots. RESULTS: Both protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68. CONCLUSION: A single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.

Challenges to the central nervous system during human spaceflight missions to Mars.

Space travel presents a number of environmental challenges to the central nervous system, including changes in gravitational acceleration that alter the terrestrial synergies between perception and action, galactic cosmic radiation that can damage sensitive neurons and structures, and multiple factors (isolation, confinement, altered atmosphere, and mission parameters, including distance from Earth) that can affect cognition and behavior. Travelers to Mars will be exposed to these environmental challenges for up to 3 years, and space-faring nations continue to direct vigorous research investments to help elucidate and mitigate the consequences of these long-duration exposures. This article reviews the findings of more than 50 years of space-related neuroscience research on humans and animals exposed to spaceflight or analogs of spaceflight environments, and projects the implications and the forward work necessary to ensure successful Mars missions. It also reviews fundamental neurophysiology responses that will help us understand and maintain human health and performance on Earth.

Effect of Recruitment of Acute Coronary Collaterals on In-Hospital Mortality and on Left Ventricular Function in Patients Presenting With ST Elevation Myocardial Infarction.

Recruitment of the coronary collateral circulation is frequently observed during ST elevation myocardial infarction (STEMI) and is of uncertain significance. The aim of this study was to identify and determine the predictors and prognostic implications of the presence of robust collaterals during STEMI. All patients presenting to a large tertiary centre with a STEMI undergoing percutaneous coronary intervention from 2010 to 2018 were reviewed. Patients with poor collateral recruitment were defined as those with Rentrop grade 0 or 1 collaterals, whilst patients with robust collateral recruitment were defined as Rentrop grade 2 or 3. A total of 1,625 patients were included in the study, with 1,280 (78.8%) patients having poor collateral recruitment and 345 patients (21.2%) having robust collateral recruitment. Patients with robust collaterals were younger (63.1 vs 65.1 years, p < 0.05), had a longer ischemic time (628.5 minutes vs 433.1 minutes, p < 0.0001), and more likely to have a chronic total occlusion of a noninfarct related artery (10.4% vs 5.3%, p < 0.001). The presence of robust collaterals was associated with higher rates of normal or mildly impaired left ventricular function (83.5% vs 63.2%, p < 0.0001) and lower in-hospital mortality (2.1% vs 7.6%, p < 0.0001). After correcting for left ventricular function, collateral recruitment was not an independent predictor of mortality. In conclusion, in patients presenting with STEMI, the presence of robust coronary collaterals appears to be associated with improved left ventricular function. Further research is required to identify mechanisms of collateral maturation and recruitment.

Impact of nonphysician providers on spatial accessibility to primary care in Iowa.

OBJECTIVE: To assess the impact of nonphysician providers on measures of spatial access to primary care in Iowa, a state where physician assistants and advanced practice registered nurses are considered primary care providers. DATA SOURCES: 2017 Iowa Health Professions Inventory (Carver College of Medicine), and minor civil division (MCD) level population data for Iowa from the American Community Survey. STUDY DESIGN: We used a constrained optimization model to probabilistically allocate patient populations to nearby (within a 30-minute drive) primary care providers. We compared the results (across 10 000 scenarios) using only primary care physicians with those including nonphysician providers (NPPs). We analyze results by rurality and compare findings with current health professional shortage areas. DATA COLLECTION/EXTRACTION METHODS: Physicians and NPPs practicing in primary care in 2017 were extracted from the Iowa Health Professions Inventory. PRINCIPAL FINDINGS: Considering only primary care physicians, the average unallocated population for primary care was 222 109 (7 percent of Iowa's population). Most of the unallocated population (86 percent) was in rural areas with low population density (< 50/square mile). The addition of NPPs to the primary care workforce reduced unallocated population by 65 percent to 78 252 (2.5 percent of Iowa's population). Despite the majority of NPPs being located in urban areas, most of the improvement in spatial accessibility (78 percent) is associated with sparsely populated rural areas. CONCLUSIONS: The inclusion of nonphysician providers greatly reduces but does not eliminate all areas of inadequate spatial access to primary care.

Altered Cognitive Flexibility and Synaptic Plasticity in the Rat Prefrontal Cortex after Exposure to Low (≤15 cGy) Doses of 28Si Radiation.

This study has established the impact that 1-15 cGy 600 MeV/n 28Si radiation had on cognitive flexibility performance, glutamatergic synaptic transmission and plasticity in the prelimbic area (PrL) of the medial prefrontal cortex (mPFC) of ∼10-month-old (at the time of irradiation) male Wistar rats. Exposure to 1 cGy 600 MeV/n 28Si ions resulted in significantly impaired performance in the simple (SD) and compound discrimination (CD) stages of the attentional set shifting (ATSET) task. However, there was a pronounced non-linear dose response for cognitive impairment. Should similar effects occur in astronauts, the impairment of SD performance would result in a decreased ability to identify and learn the "rules" required to respond to new tasks/situations, while the impaired CD performance would result in a decreased ability to identify and maintain focus on relevant aspects of the task being conducted. The irradiated rats were also screened for performance in a task for unconstrained cognitive flexibility (UCFlex), often referred to as creative problem solving. Exposure to 1, 5 and 10 cGy resulted in a significant reduction in UCFlex performance, in an apparent all-or-none responsive manner. Importantly, performance in the ATSET test was not indicative of UCFlex performance. From a risk assessment perspective, these findings suggest that a value based on a single behavioral end point may not fully represent the cognitive deficits induced by space radiation, even within the cognitive flexibility domain. After completion of the cognitive flexibility testing, in vitro electrophysiological assessments of glutamatergic synaptic transmission and plasticity were performed in slices of the PrL cortex of 10 cGy irradiated rats. Extracellular recordings of field excitatory postsynaptic potentials revealed that radiation significantly decreased long-term depression in layer L5. Patch-clamp whole cell recordings in pyramidal neurons of the L2-3 revealed reduced frequency of spontaneous excitatory postsynaptic currents indicating alterations in presynaptic glutamate release and impaired neuronal spiking (e.g., decreased action potential amplitudes) in irradiated neurons. However, there was no obvious correlation between magnitudes of these electrophysiological decrements and the cognitive performance status of the irradiated rats. These data suggest that while radiation-induced changes in synaptic plasticity in the PrL cortex may be associated with cognitive impairment, they are most likely not the sole determinant of the incidence and severity of such impairments.

Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.

PURPOSE: Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation. MATERIALS AND METHODS: Male C57BL/6 J mice were exposed to oxygen ions (16O, 600 MeV/n at 0.25-0.26 Gy/min to a total dose of 0, 0.05, 0.1, 0.25, or 1 Gy), protons (150 MeV, 0.35-0.55 Gy/min to 0, 0.5, or 1 Gy), or protons (150 MeV, 0.5 Gy) followed by 16O (600 MeV/n, 0.1 Gy). Separate groups of mice received 137Cs γ-rays (1 Gy/min to 0, 0.5, 1, or 3 Gy) as a reference. Cardiac function and blood velocity were measured with ultrasonography at 3, 5, 7, and 9 months after irradiation. At 2 weeks, 3 months, and 9 months, cardiac tissue was collected to assess apoptosis, tissue remodeling, and markers of immune cells. RESULTS: Ejection fraction and fractional shortening decreased at 3 and 7 months after 16O. These parameters did not change in mice exposed to γ-rays, protons, or protons followed by 16O. Each of the radiation exposures caused only small increases in cleaved caspase-3 and numbers of apoptotic nuclei. Changes in the levels of α-smooth muscle cell actin and a 75-kDa peptide of collagen type III in the left ventricle suggested tissue remodeling, but there was no significant change in total collagen deposition at 2 weeks, 3 months, and 9 months. Increases in protein amounts of cluster of differentiation (CD)2, CD68, and CD45 as measured with immunoblots at 2 weeks, 3 months, and 9 months after exposure to protons or 16O alone suggested immune cell infiltration. For type III collagen, CD2 and CD68, the efficacy in inducing protein abundance of CD2, CD68, and CD45 was 16O > protons > γ-rays > protons followed by 16O. CONCLUSIONS: Low-dose, high-energy charged-particle irradiation caused mild changes in cardiac function and tissue remodeling in the mouse.

The workforce trends of physician assistants in Iowa (1995-2015).

BACKGROUND: Physician assistants are expected to have an important role in providing both primary and specialty care. Iowa has a large rural (and aging) population and faces challenges to provide equitable access to care. This study examined changes in the Iowa physician assistant workforce (1995-2015) focusing on practice setting (primary v. subspecialty care) and geographic location (rural/urban, Health Professional Shortage Area). Documenting their current locations and service in HPSAs for primary care will help health planners track future changes. METHODS: Data from 1995-2015 from the Iowa Health Professions Inventory (Office of Statewide Clinical Education Programs, Carver College of Medicine, University of Iowa) were combined with US census data on rural location and HPSA status. SPSS was used to compare Iowa and national data. Growth trends were analyzed using joinpoint regression. RESULTS: The overall Iowa physician assistant workforce increased 161% between 1995 and 2015. In 2015, more than two-thirds (71%) were female and more than 30% practiced in rural counties. The average annual growth rate of primary care PAs (per 100,000 population) was significantly higher in the periods from 1995-1997 and 1997-2001 (22.4% and 7.4% respectively) than in period from 2001-2015 (3.8%). By 2015, 56% of Iowa's physician assistants practiced in primary care (versus 29.6% nationally). Of these, 44% of primary care physician assistants in Iowa practiced in counties, geographic locations or worksites designated as Health Professional Shortage Areas for primary care. CONCLUSIONS: A high proportion of Iowa's physician assistant workforce practiced in primary care and many served patients in Health Professional Shortage Areas. The number of physician assistants in Iowa will continue to grow and serve an important role in providing access to health care, particularly to rural Iowans.

Female mice are protected from space radiation-induced maladaptive responses.

Interplanetary exploration will be humankind's most ambitious expedition and the journey required to do so, is as intimidating as it is intrepid. One major obstacle for successful deep space travel is the possible negative effects of galactic cosmic radiation (GCR) exposure. Here, we investigate for the first time how combined GCR impacts long-term behavioral and cellular responses in male and female mice. We find that a single exposure to simulated GCR induces long-term cognitive and behavioral deficits only in the male cohorts. GCR exposed male animals have diminished social interaction, increased anxiety-like phenotype and impaired recognition memory. Remarkably, we find that the female cohorts did not display any cognitive or behavioral deficits after GCR exposure. Mechanistically, the maladaptive behavioral responses observed only in the male cohorts correspond with microglia activation and synaptic loss in the hippocampus, a brain region involved in the cognitive domains reported here. Furthermore, we measured reductions in AMPA expressing synaptic terminals in the hippocampus. No changes in any of the molecular markers measured here are observed in the females. Taken together these findings suggest that GCR exposure can regulate microglia activity and alter synaptic architecture, which in turn leads to a range of cognitive alterations in a sex dependent manner. These results identify sex-dependent differences in behavioral and cognitive domains revealing promising cellular and molecular intervention targets to reduce GCR-induced chronic cognitive deficits thereby boosting chances of success for humans in deep space missions such as the upcoming Mars voyage.

Author Correction: Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

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Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

Peripheral T Cells as a Biomarker for Oxygen-Ion-Radiation-Induced Social Impairments.

Exposure to galactic cosmic rays (GCR) poses an obstacle to successful deep space missions, including missions to the Moon or Mars. Previously, we and others have identified chronic cognitive impairments associated with GCR in rodent model systems. The persistent cognitive loss previously reported is indicative of global changes in different regions of the brain, including the prefrontal cortex and the hippocampus. It has been shown that both of these brain regions are involved in social functions. Here we demonstrate that four months after a single exposure to oxygen ionizing radiation, which is a component of GCR, adult male mice have social memory deficits. Importantly, we identified circulating levels of CD8 T cells as predictors of social behavioral changes. Thus, CD8 T cells could be used as a potential peripheral biomarker. To the best of our knowledge we demonstrate for the first time that GCR-induced impairments in social behavior are directly linked to peripheral immune changes. These results further advance our understanding of the challenges encountered during space exploration.