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At least 883 records · Page 49

Resting Energy Expenditure of Rats Acclimated to Hyper-Gravity

To determine the influence of body mass and age on resting energy expenditure (EE) following acclimation to hyper-gravity, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured to calculate resting energy expenditure (EE), in male rats, ages 40 to 400 days, acclimated to 1.23 or 4.1 G for a minimum of two weeks. Animals were maintained on a centrifuge to produce the hyper-gravity environment. Measurements were made over three hours in hyper-gravity during the period when the lights were on, the inactive period of rats. In rats matched for body mass (approximately 400 g) hyper-gravity increased VO2 by 18% and VCO2 by 27% compared to controls, resulting in an increase in RER, 0.80 to 0.87. There were increases in resting EE with an increase in gravity. This increase was greater when the mass of the rat was larger. Rating EE for 400g animals were increased from 47 +/- 1 kcal/kg/day at 1 G, to 57 +/- 1.5 and 5.8 +/- 2.2 kcal/kg/day at 2,3 and 4.1 G, respectively. There was no difference between the two hyper-gravity environments. When differences in age of the animals were accounted for, the increase in resting EE adjusted for body mass was increased by over 36% in older animals due to exposure to hyper-gravity. Acclimation to hyper-gravity increases the resting EE of rats, dependent upon body mass and age, and appears to alter substrate metabolism. Increasing the level of hyper-gravity, from 2.3 to 4.1 G, produced no further changes raising questions as to a dose effect of gravity level on resting metabolism.

Wade, Charles E.↗

The Influence of Sound Cues on the Maintenance of Temporal Organization in the Sprague-Dawley Rat

Temporal organization is a fundamental property of living matter. From single cells to complex animals including man, most physiological systems undergo daily periodic changes in concert with environmental cues (e.g., light, temperature etc.). It is known that pulsed Environmental synchronizers, zeitgebers, (e.g. light) can modify rhythm parameters. Rhythm stability is a necessary requirement for most animal experiments. The extent to which sound can influence the circadian system of laboratory rats is poorly understood. This has implications to animal habitats in the novel environments of the Space-Laboratory or Space Station. A series of three white noise (88+/-0.82 db) zeitgeber experiments were conducted (n=6/experiment).The sound cue was introduced in the circadian free-running phase (DD-NQ) and in one additional case sound was added to the usual photoperiod (12L:12D) to determine masking effects. Circadian rhythm parameters of drinking frequency, feeding frequency, and gross locomotor activity were continuously monitored. Data analysis for these studies included macroscopic and microscopic methods. Raster plots to visually detect entrainment versus free-running period, were plotted for each animal, for all three parameters, during all sound perturbation tested. These data were processed through a series of detrending (robust locally weighted regression analyses) and complex demodulation analyses. In summary, these findings show that periodic "white" noise "influences" the rats circadian system but does not "entrain" the feeding, drinking or locomotor activity rhythms.

Winget, C. M.↗

Effect of Actual and Simulated Microgravity on Cardiac Mass and Function in the Rat

The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hin~limb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.

Ray, Chester H.↗

Effects of Chronic 2.0% and 0.7% CO2 Exposures on the Well-Being, Growth and Renal Function of Rats

On the Space Shuttle and MIR, mean CO2 levels have been 0.3% which is ten times that of normal air. There have also been extended periods with levels of 0.7% CO2 with peak concentrations at 2.0%. The Space Station program had proposed that CO2 concentration levels be maintained, on average, at 0.7%, and not to exceed 1.0%. To ensure that these levels of CO2 would not compromise the integrity of the science performed on the Space Station, the effects of chronic exposure of rats to 2.0% and 0.7% CO2 were investigated. Ten male rats per group were placed in individual metabolic cages for monitoring of food and water consumption, as well as fecal and urine production. Cages were placed in a large (4W x 10L x 4H ft.) plexiglass chamber with a controlled atmospheric environment. Following 7 days of cage adaptation, animals were exposed to experimental (2.0% or 0.7% CO2) or control (ambient air) conditions for 30 days. Daily body weight, food and water intake, and fecal and urine excretions were measured for the last three days of adaptation and the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH and total CO2. During 2.0% and 0.7% CO2 exposures, animal growth, fecal production and food and water consumption were within normal ranges. Urine excretion was significantly (p less than 0.05) higher in both experimental groups compared to controls. Urine pH of animals exposed to 2.0% CO2 was decreased by 0.32 over the first 6 days of exposure, followed by a 0.63 increase by day 30. In animals exposed to 0.7% CO2, urine pH did not decrease early in the exposure period, but did increase by 0.37 by day 30. Urine CO2 excretion did not change the first 6 days of exposure, but significantly increased in both 2.0% and 0.7% CO2 by day 30 (897 and 402 mmol/day, respectively). These results of chronic exposure to 2.0% and 0.7% CO2 are consistent with renal compensation in response to an altered acid-base homeostasis. These findings may impact science conducted on the Space Shuttle or the Space Station if CO2 concentrations reach 0.7%.

Lang, C. K.↗

National Institutes of Health, Rodent 4 (NIH.R4); Calcium Metabolism and Vascular Function After Spaceflight: A Collaborative Series with NASA and NIH

The NIH.R4 payload was a collaborative experiment conducted by NASA's Ames Research Center in conjunction with the National Institutes of Health (NIH). This middeck payload was the fourth in a series of experiments focusing on developmental biology and the effects of microgravity on mammalian systems. The NIH.R4 payload was flown onboard STS-80, which launched November 19, 1996, and landed at Kennedy Space Center on December 7, 1996, and was the longest shuttle mission to date. Fourteen male Spontaneously Hypertensive rats (SHR) were flown; seven in each of two Animal Enclosure Modules (AEM) in the shuttle middeck. The flight animals were exposed to 18 days of microgravity. Two synchronous control groups were utilized for this study in addition to an asynchronous post-flight AEM control study conducted at the PI lab. The animals were fed two different calcium diets in the NASA food bar (2.0% and 0.2%) three weeks prior to launch and insight. Blood pressures were taken at pre-determined intervals and were the basis for flight selection. Upon recovery Dwight animals blood pressure was measured and a variety of tissues were collected. Project testing and data will be presented.

Reiss-Bubenheim, Debra↗

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

Adams, Gregory A.↗

Chemically Defined Medium and Caenorhabditis elegans: A Powerful Approach

C. elegans has been established as a powerful genetic system. Growth in a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of me in large-scale growth and screening of animals. Here we present our initial results from developing culture systems with CeMM. We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats of using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change defined medium composition. As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

Szewczyk, N. J.↗

Covisualization by computational optical-sectioning microscopy of integrin and associated proteins at the cell membrane of living onion protoplasts

Using higher-resolution wide-field computational optical-sectioning fluorescence microscopy, the distribution of antigens recognized by antibodies against animal beta 1 integrin, fibronectin, and vitronectin has been visualized at the outer surface of enzymatically protoplasted onion epidermis cells and in depectinated cell wall fragments. On the protoplast all three antigens are colocalized in an array of small spots, as seen in raw images, in Gaussian filtered images, and in images restored by two different algorithms. Fibronectin and vitronectin but not beta 1 integrin antigenicities colocalize as puncta in comparably prepared and processed images of the wall fragments. Several control visualizations suggest considerable specifity of antibody recognition. Affinity purification of onion cell extract with the same anti-integrin used for visualization has yielded protein that separates in SDS-PAGE into two bands of about 105-110 and 115-125 kDa. These bands are again recognized by the visualization antibody, which was raised against the extracellular domain of chicken beta 1 integrin, and are also recognized by an antibody against the intracellular domain of chicken beta 1 integrin. Because beta 1 integrin is a key protein in numerous animal adhesion sites, it appears that the punctate distribution of this protein in the cell membranes of onion epidermis represents the adhesion sites long known to occur in cells of this tissue. Because vitronectin and fibronection are matrix proteins that bind to integrin in animals, the punctate occurrence of antigenically similar proteins both in the wall (matrix) and on enzymatically prepared protoplasts reinforces the concept that onion cells have adhesion sites with some similarity to certain kinds of adhesion sites in animals.

NASA Discipline Plant Biology↗

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Kramer, George C.↗

Solar System Visualizations

Solar System Visualization products enable scientists to compare models and measurements in new ways that enhance the scientific discovery process, enhance the information content and understanding of the science results for both science colleagues and the public, and create.visually appealing and intellectually stimulating visualization products. Missions supported include MER, MRO, and Cassini. Image products produced include pan and zoom animations of large mosaics to reveal the details of surface features and topography, animations into registered multi-resolution mosaics to provide context for microscopic images, 3D anaglyphs from left and right stereo pairs, and screen captures from video footage. Specific products include a three-part context animation of the Cassini Enceladus encounter highlighting images from 350 to 4 meter per pixel resolution; Mars Reconnaissance Orbiter screen captures illustrating various instruments during assembly and testing at the Payload Hazardous Servicing Facility at Kennedy Space Center; and an animation of Mars Exploration Rover Opportunity's 'Rub al Khali' panorama where the rover was stuck in the deep fine sand for more than a month. This task creates new visualization products that enable new science results and enhance the public's understanding of the Solar System and NASA's missions of exploration.

Brown, Alison M.↗

Online Visualization and Analysis of Merged Global Geostationary Satellite Infrared Dataset

The NASA Goddard Earth Sciences Data Information Services Center (GES DISC) is home of Tropical Rainfall Measuring Mission (TRMM) data archive. The global merged IR product also known as the NCEP/CPC 4-km Global (60 degrees N - 60 degrees S) IR Dataset, is one of TRMM ancillary datasets. They are globally merged (60 degrees N - 60 degrees S) pixel-resolution (4 km) IR brightness temperature data (equivalent blackbody temperatures), merged from all available geostationary satellites (GOES-8/10, METEOSAT-7/5 and GMS). The availability of data from METEOSAT-5, which is located at 63E at the present time, yields a unique opportunity for total global (60 degrees N- 60 degrees S) coverage. The GES DISC has collected over 8 years of the data beginning from February of 2000. This high temporal resolution dataset can not only provide additional background information to TRMM and other satellite missions, but also allow observing a wide range of meteorological phenomena from space, such as, mesoscale convection systems, tropical cyclones, hurricanes, etc. The dataset can also be used to verify model simulations. Despite that the data can be downloaded via ftp, however, its large volume poses a challenge for many users. A single file occupies about 70 MB disk space and there is a total of approximately 73,000 files (approximately 4.5 TB) for the past 8 years. In order to facilitate data access, we have developed a web prototype to allow users to conduct online visualization and analysis of this dataset. With a web browser and few mouse clicks, users can have a full access to over 8 year and over 4.5 TB data and generate black and white IR imagery and animation without downloading any software and data. In short, you can make your own images! Basic functions include selection of area of interest, single imagery or animation, a time skip capability for different temporal resolution and image size. Users can save an animation as a file (animated gif) and import it in other presentation software, such as, Microsoft PowerPoint. The prototype will be integrated into GIOVANNI and existing GIOVANNI capabilities, such as, data download, Google Earth KMZ, etc will be available. Users will also be able to access other data products in the GIOVANNI family.

Liu, Zhong↗

A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice receiving only 2 Gy of protons. Tissue of the gastrointestinal tract was also homogenized and RNA was isolated for cDNA synthesis and real-time PCR analysis. Inspecting apoptotic lesions of the duodenum of the small intestine as an endpoint of damage did not reveal a radio-adaptive response in C57BL/6 mice at the four hour time point. Results of gene expression changes showed consistent up or down regulation of a number of genes for all of the exposure doses that may play a role in proton-induced apoptosis. Preliminary results of gene expression alterations as a result of gamma-irradiation revealed a wealth of genes involved in oxidative stress and antioxidant defense processes being up- or down-regulated only at the highest exposure dose of 6 Gy and the combined dose of 5 cGy with 6 Gy. Those animals undergoing only 5 cGy of gamma-irradiation showed very little modification of gene expression. Taken together these results lead us to conclude that protons cause more severe morphologic damage to the duodenum of the small intestine at a dose of 2 Gy than a higher dose of 6 Gy of gamma rays to the same organ. Both protons and gamma rays lead to significant variation in gene expression at high doses in the small intestine and these changes may provide insight into the mechanism of injury seen in the gastrointestinal tract following radiation exposure. Astronauts experiencing prolonged exposure to protons in the low Earth orbit and in deep space, and experiencing acute exposure to protons from solar particle events, may face biological consequences that will impact a mission s success. We will continue this work by studying, quantifying, and comparing damage due to protons and gamma rays in the small intestine as well as other organs in a time-dependent manner.

Purgason, Ashley↗

Hurricane Data Analysis Tool

In order to facilitate Earth science data access, the NASA Goddard Earth Sciences Data Information Services Center (GES DISC) has developed a web prototype, the Hurricane Data Analysis Tool (HDAT; URL: http://disc.gsfc.nasa.gov/HDAT), to allow users to conduct online visualization and analysis of several remote sensing and model datasets for educational activities and studies of tropical cyclones and other weather phenomena. With a web browser and few mouse clicks, users can have a full access to terabytes of data and generate 2-D or time-series plots and animation without downloading any software and data. HDAT includes data from the NASA Tropical Rainfall Measuring Mission (TRMM), the NASA Quick Scatterometer(QuikSCAT) and NECP Reanalysis, and the NCEP/CPC half-hourly, 4-km Global (60 N - 60 S) IR Dataset. The GES DISC archives TRMM data. The daily global rainfall product derived from the 3-hourly multi-satellite precipitation product (3B42 V6) is available in HDAT. The TRMM Microwave Imager (TMI) sea surface temperature from the Remote Sensing Systems is in HDAT as well. The NASA QuikSCAT ocean surface wind and the NCEP Reanalysis provide ocean surface and atmospheric conditions, respectively. The global merged IR product, also known as, the NCEP/CPC half-hourly, 4-km Global (60 N -60 S) IR Dataset, is one of TRMM ancillary datasets. They are globally-merged pixel-resolution IR brightness temperature data (equivalent blackbody temperatures), merged from all available geostationary satellites (GOES-8/10, METEOSAT-7/5 & GMS). The GES DISC has collected over 10 years of the data beginning from February of 2000. This high temporal resolution (every 30 minutes) dataset not only provides additional background information to TRMM and other satellite missions, but also allows observing a wide range of meteorological phenomena from space, such as, hurricanes, typhoons, tropical cyclones, mesoscale convection system, etc. Basic functions include selection of area of interest and time, single imagery, overlay of two different products, animation,a time skip capability and different image size outputs. Users can save an animation as a file (animated gif) and import it in other presentation software, such as, Microsoft PowerPoint. Since the tool can directly access the real data, more features and functionality can be added in the future.

Liu, Zhong↗

CloudSat Reflectivity Data Visualization Inside Hurricanes

Animations and other outreach products have been created and released to the public quickly after the CloudSat spacecraft flew over hurricanes. The automated script scans through the CloudSat quicklook data to find significant atmospheric moisture content. Once such a region is found, data from multiple sources is combined to produce the data products and the animations. KMZ products are quickly generated from the quicklook data for viewing in Google Earth and other tools. Animations are also generated to show the atmospheric moisture data in context with the storm cloud imagery. Global images from GOES satellites are shown to give context. The visualization provides better understanding of the interior of the hurricane storm clouds, which is difficult to observe directly. The automated process creates the finished animation in the High Definition (HD) video format for quick release to the media and public.

visualization↗

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water-selective channel involved in interstitial fluid homeostasis, showed an upregulated trend in HS retinas; however, these results are preliminary. Total retinal thickness increased significantly (P = 0.049) in HS rats fed a resveratrol enriched diet compared to HS rats on a normal diet. This change appeared to be reversed during the 2 weeks of recovery post HS, but no differences in retina thickness were observed between HS animals and HS recovered animals when both groups consumed a normal diet. The reversibility of the increase in retinal thickness induced by resveratrol during HS may therefore reflect an interaction between the stress provoked by HS and the cytoprotective mechanisms elicited by resveratrol

Glass, Aziza↗

Space Radiation Program Element Tissue Sharing Initiative

Over the years, a large number of animal experiments have been conducted at the NASA Space Radiation Laboratory and other facilities under the support of the NASA Space Radiation Program Element (SRPE). Studies using rodents and other animal species to address the space radiation risks will remain a significant portion of the research portfolio of the Element. In order to maximize scientific return of the animal studies, SRPE is taking the initiative to promote tissue sharing among the scientists in the space radiation research community. This initiative is enthusiastically supported by the community members as voiced in the responses to a recent survey. For retrospective tissue samples, an online platform will be established for the PIs to post a list of the available samples, and to exchange information with the potential recipients. For future animal experiments, a tissue sharing policy is being developed by SRPE.

Wu, H.↗

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗

Group Housing During Hindlimb Unloading to Simulate Weightlessness

The rodent hindlimb unloading (HU) model was developed in the 1980s to faciliate the study of mechanisms, responses, and treatments for the adverse effects of spaceflight. A number of variations on unloading systems and cage designs have been developed, although most entail individually housing the HU animals. In this study, we performed hindlimb unloading under group housing conditions. Our preliminary results indicate that HU animals that were group housed for 30 days, displayed musculoskeletal decrements associated with disuse, and further, body weights did not differ compared to age-matched controls. In conclusion, group housing of HU mice provides a novel means to simulate weightlessness under conditions that more closely resemble living conditions of Rodent Research Project ISS flight hardware habitats, and minimizes the social stress of isolation, which is consistent with current animal welfare standards (Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Research Council).

group housing↗