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67 records · Page 4

Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887

We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

NASA Experiment Number COS 1887-33↗

Development of a Methodology to Gather Seated Anthropometry in a Microgravity Environment

The Constellation Program's Crew Exploration Vehicle (CEV) is required to accommodate the full population range of crewmembers according to the anthropometry requirements stated in the Human-Systems Integration Requirement (HSIR) document (CxP70024). Seated height is one of many critical dimensions of importance to the CEV designers in determining the optimum seat configuration in the vehicle. Changes in seated height may have a large impact to the design, accommodation, and safety of the crewmembers. Seated height can change due to elongation of the spine when crewmembers are exposed to microgravity. Spinal elongation is the straightening of the natural curvature of the spine and the expansion of inter-vertebral disks. This straightening occurs due to fluid shifts in the body and the lack of compressive forces on the spinal vertebrae. Previous studies have shown that as the natural curvature of the spine straightens, an increase in overall height of 3% of stature occurs which has been the basis of the current HSIR requirements. However due to variations in the torso/leg ratio and impact of soft tissue, data is nonexistent as to how spinal elongation specifically affects the measurement of seated height. In order to obtain this data, an experiment was designed to collect spinal elongation data while in a seated posture in microgravity. The purpose of this study was to provide quantitative data that represents the amount of change that occurs in seated height due to spinal elongation in microgravity environments. Given the schedule and budget constraints of ISS and Shuttle missions and the uniqueness of the problem, a methodology had to be developed to ensure that the seated height measurements were accurately collected. Therefore, simulated microgravity evaluations were conducted to test the methodology and procedures of the experiment. This evaluation obtained seat pan pressure and seated height data to a) ensure that the lap restraint provided sufficient restraint to eliminate any gap between the subject s gluteal surface and the seat pan and b) to document any necessary design and procedural changes needed due to the microgravity environment. The methodology and setup used during the simulated microgravity evaluations was replicable to the proposed methodology and setup for in-space missions. A flight-like Shuttle seat, pressure sensors, anthropometer, and existing hardware was used to measure seated height and contact area while experiencing microgravity. The outlying buttock and thigh surface contact areas were collected to determine if the subjects were in contact with the seat pan, while a measurer recorded their seated height with an anthropometer. The Anthropometry and Biomechanics Facility (ABF) completed data collection from three microgravity flights to assess the restraint methods and techniques to be used for the in-flight procedures performed by the crewmembers in orbit. The first flight demonstrated that the restraint system on the seat, used in a nominal configuration, did not sufficiently restrain a person in the seat. The results showed the subjects were not in full contact with the seat pan, resulting in inaccurate sitting height data. Thus, a second flight was conducted to test different restraint system options. The results showed that by 1) changing the restraint system from the nominal 3-points of the 5-point harness, which is used for crewmembers when fully suited with emergency equipment, and 2) rerouting the lap straps around the joint of the backrest, where the backrest and seat pan are joined, resulted in the optimal method to restrain a subject. This rerouting method allowed for the anchor location to change and pull the subjects back into the seat instead of being anchored at the side of the subjects thighs. The results from the third flight validated the final restraint system, which resulted in a verified methodology for collecting seated anthropometry to ultimately determine the amount of spil elongation in a microgravity environment.

Rajulu, Sudhakar↗

Potential Dietary Countermeasure Against Spaceflight-Induced Bone Loss

As humans venture further into space and beyond low Earth orbit, space radiation is one of the main challenges for astronauts' health. Radiation-induced bone loss is a potential health problem for long duration habitation in space. We showed that a dietary countermeasure prevents bone loss in mice exposed to total body irradiation (TBI). We used a range of ionizing radiation, gamma (137Cs), proton (1H), iron (56Fe), and a combination of sequential proton and iron beam (1H/56Fe/1H) to evaluate skeletal responses. These TBI cover a range of linear energy transfer (LET), from low-LET such as proton, to high-LET such as 56Fe (HZE: high Z- high energy) at doses between 1-2 Gy. The countermeasure diet, composed of 25% Dried Plum (DP) was effective at preventing radiation-induced cancellous bone loss in appendicular bone (tibia). Furthermore, exposing mice to HZE radiation, such as 56Fe (1Gy), impaired ex vivo growth of marrow-derived, bone-forming osteoblasts, which led to reduced mineralization capacity (-77%). In contrast, mice fed the DP diet did not display these deficits, showing the diet's capacity to protect marrow-derived osteoprogenitors. Dietary DP prevented the increase of bone resorbing osteoclast cells, inflammation and oxidative stress, while protecting the osteoprogenitors and mesenchymal stem cells, which few drugs against osteoporosis may achieve. Spaceflight is a combination of multiple factors including microgravity, in addition to space radiation. Therefore, we conducted additional studies to determine if the DP diet could prevent simulated spaceflight (simulated microgravity and radiation combined) bone loss. Mice were exposed to gamma (TBI, 137Cs, 2 Gy), simulated microgravity (using the hindlimb unloading system, HU) or TBI+HU. While we observed bone loss in mice fed the control diet (CD) due to both treatments (TBI=14%, HU=20%), and a worse effect with combined treatments (TBI+HU=25%), mice fed the DP diet did not sustain significant bone loss relative to untreated controls. The DP diet prevented microarchitectural decrements in both appendicular bone (tibia) and axial bone (vertebrae). In addition, the DP diet mitigated HU-induced deficits in osteoblastogenesis. Interestingly, lower doses of DP diet (5%, 10%) did not appear to prevent cancellous bone loss, which shows the importance of identifying the active component(s) of DP. Finally, we have preliminary data showing the potential of DP to prevent radiation-induced damage at a systematic level.. In summary, this novel dietary countermeasure is a promising candidate nutritional countermeasure for spaceflight-induced bone loss and tissue damage.

Countermeasure↗

Prevention of Spaceflight-Induced Bone Loss: A Promising Dietary Countermeasure

Space radiation is one of the challenges for long-term spaceflight, especially for missions beyond low Earth Orbit. We have shown that a diet composed of 25% dried plum (DP) prevents radiation-induced bone loss. The DP diet fully protected the cancellous bone microarchitecture of mice exposed to ionizing radiation (gamma, proton, and HZE). In particular relevant to space radiation, we showed that the DP diet prevents bone loss due to 1Gy of sequential exposure of proton (1H, low linear energy transfer -LET-), and 1Gy of iron (56Fe, high-LET). In addition, total body exposure to 1Gy of HZE radiation (56Fe) impaired the osteoprogenitors in mice fed the control diet, as indicated by decreased osteoblast mineralization. In contrast, marrow stem cells from mice fed the DP did not exhibit these deficits. Based on these promising results supporting DP as a countermeasure to prevent space radiation induced-tissue damage, we conducted additional studies to combine radiation and simulated microgravity. We exposed skeletally mature male mice to simulated microgravity (using hindlimb unloading, HU) or total body irradiation (TBI, 2Gy 137Cs) or in combination (HU+TBI). We observed bone loss in the mice fed the control diet (CD) exposed to simulated spaceflight, as measured by cancellous bone microarchitecture parameters such as percent bone volume (BV/TV). In contrast, mice fed the DP diet did not exhibit similar bone loss with either treatments (HU or TBI) or combined (HU+TBI) as seen in most parameters. This was observed in both long bones (tibia) and axial bones (vertebrae). Furthermore, preliminary data shows that pre-feeding with the DP diet attenuates the HU-induced decrement in bone-forming osteoblasts colony counts and mineralization capacity of the osteoprogenitor cells. We also performed DP feeding at lower doses (5%, 10%) and found that these doses are less effective in preventing the radiation-induced bone loss. All our studies with the DP diet as a countermeasure were done with a period of pre-feeding ranging from 14 to 21 days before irradiation, and in order to test the capacity of the DP diet as a countermeasure provided after exposure to radiation, we exposed mice to 2Gy gamma radiation and then provided the DP diet 24 hours post-IR. Preliminary data indicates that DP mitigated the radiation-induced deficits in certain cancellous bone structural parameters. Finally, we showed that mice fed with the control diet (CD) increased oxidative damage in the serum after radiation exposure, whereas mice fed the DP diet do did not show such an increase. In summary, the DP diet is a promising countermeasure for spaceflight-induced tissue damage.

Schreurs, Ann-Sofie↗

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

NASA Discipline Regulatory Physiology↗

Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (D{sub max}) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD2{sub 2}) D{sub max} ≤70 Gy; SBRT thecal sac EQD2{sub 2} D{sub max} ≤25 Gy, thecal sac SBRT EQD2{sub 2} D{sub max} to cumulative EQD2{sub 2} D{sub max} ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model

Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

miR-31-5p promotes proliferation and inhibits apoptosis of goat hair follicle stem cells by targeting RASA1/MAP3K1 pathway

Highlights: • MAP3K1 was upregulated in hair follicle stem cells in response to overexpression miR-31–5p. • We confirmed RASA1 as a target gene of miR-31–5p. • Inhibition of miR-31–5p promotes apoptosis. • The miR-31–5p/RASA1/MAP3K1 axis regulates hair follicle stem cells activity via MAPK pathway. The Yangtze River Delta white goat is a sole goat species that can naturally produce superior-quality brush hair. It's worth to mention that study the developmental mechanism of goat hair follicle stem cells is vital for future breed preservation and molecular breeding. In this study, we successfully isolated hair follicle stem cells from the skin tissue of fetal sheep neck spine, and harvested superior-quality and normal-quality brush hair goat tissue. The expression of miR-31-5p in goat hair follicle stem cells was verified by qPCR and Western blot. The effects of overexpression or inhibition of miR-31-5p on the proliferation and apoptosis of hair follicle stem cells were detected by EdU, CCK-8, flow cytometry, etc. miR-31-5p can significantly improve cell proliferation and inhibit cell apoptosis by targeting RASA1 and upregulating MAP3K1 level, whereas miR-31-5p knockdown led to an opposite effect. These results reveal a miR-31-5p-associated regulatory network between miR-31-5p and RASA1/MAP3K1 during the progression of superiorquality brush hair traits.

60 APPLIED LIFE SCIENCES↗

Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that “run through” the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90 Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949–1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90 Sr and 89 Sr intake to humans.

59 BASIC BIOLOGICAL SCIENCES↗

Vestibulospinal control of reflex and voluntary head movement

Secondary canal-related vestibulospinal neurons respond to an externally applied movement of the head in the form of a firing rate modulation that encodes the angular velocity of the movement, and reflects in large part the input "head velocity in space" signal carried by the semicircular canal afferents. In addition to the head velocity signal, the vestibulospinal neurons can carry a more processed signal that includes eye position or eye velocity, or both (see Boyle on ref. list). To understand the control signals used by the central vestibular pathways in the generation of reflex head stabilization, such as the vestibulocollic reflex (VCR), and the maintenance of head posture, it is essential to record directly from identified vestibulospinal neurons projecting to the cervical spinal segments in the alert animal. The present report discusses two key features of the primate vestibulospinal system. First, the termination morphology of vestibulospinal axons in the cervical segments of the spinal cord is described to lay the structural basis of vestibulospinal control of head/neck posture and movement. And second, the head movement signal content carried by the same class of secondary vestibulospinal neurons during the actual execution of the VCR and during self-generated, or active, rapid head movements is presented.

Review, Tutorial↗

Sensory processing in the vestibular nuclei during active head movements

Many secondary vestibular neurons are sensitive to head on trunk rotation during reflex-induced and voluntary head movements. During passive whole body rotation the interaction of head on trunk signals related to the vestibulo-collic reflex with vestibular signals increases the rotational gain of many secondary vestibular neurons, including many that project to the spinal cord. In some units, the sensitivity to head on trunk and vestibular input is matched and the resulting interaction produces an output that is related to the trunk velocity in space. In other units the head on trunk inputs are stronger and the resulting interaction produces an output that is larger during the reflex. During voluntary head movements, inputs related to head on trunk movement combine destructively with vestibular signals, and often cancel the sensory reafferent consequences of self-generated movements. Cancellation of sensory vestibular signals was observed in all of the antidromically identified secondary vestibulospinal units, even though many of these units were not significantly affected by reflexive head on trunk movements. The results imply that the inputs to vestibular neurons related to head on trunk rotation during reflexive and voluntary movements arise from different sources. We suggest that the relative strength of reflexive head on trunk input to different vestibular neurons might reflect the different functional roles they have in controlling the posture of the neck and body.

Non-NASA Center↗

Bone mineral density, muscle strength, and recreational exercise in men

Muscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual-energy x-ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p < 0.01 to p = 0.0001). Body weight correlated with tibia and whole-body BMD (p < 0.001); age negatively correlated with Ward's triangle BMD (p < 0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2 = 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35-52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5) years, and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercises than in nonexercisers.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Center ARC↗

Murine Spine Composition and Mechanics are Maintained After 30-Days of Spaceflight

As NASA prepares to send astronauts on deep space missions, understanding the detrimental effects of spaceflight on the body is imperative. Spaceflight is known to negatively affect the spine, with astronauts experiencing systemic bone loss and increased post-flight risk of intervertebral disc herniation. Space investigations with rodent models have characterized some of the effects of spaceflight on the mammalian body, but variable experimental conditions have made it difficult to cohesively interpret results. These conditions include housing, flight duration, and for the spine, anatomical location. Thus, the objective of this study was to comprehensively characterize the effects of spaceflight on the bulk properties of the murine lumbar spine. To do this, we examined the lumbar spine of mice flown on the NASA Rodent Research 10 mission and analyzed disc biochemical content, disc joint material properties, lumbar vertebral body microarchitecture, and proximal tibia microarchitecture. Finally, we qualitatively examined bone growth in the vertebral bodies using confocal microscopy and on-orbit injections of calcein. Contrary to prior results, we found little to no effect of spaceflight on lumbar spine properties. Spaceflight, however, did negatively affect both cortical and trabecular bone properties of the proximal tibia load-bearing site. We hypothesize that this may be due to loading associated with increased physical activity in the second half of the mission, observed on in-flight videos, that reload the lumbar spine as mice utilize quadruped ambulation. This increased activity occurs after an initial period of relative inactivity in microgravity. In support of this hypothesis, we observed new L5 bone formation in the last seven days of spaceflight, suggesting that current 30-day experimental flight conditions may not be as effective at lumbar spine unloading as previous shorter flights.

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