SEARCH · Search NASA

Results for “Hindlimb Suspension”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6

All sources NASA NTRS DOE OSTI

NASA NTRS2003

Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle

c-Jun NH(2)-terminal kinase (JNK) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate-1 (IRS-1) in adipose and liver tissue. Using a rat hindlimb suspension model for muscle disuse atrophy, we found that JNK activity was significantly elevated in atrophic soleus muscle and that IRS-1 was phosphorylated on Ser(307) prior to the degradation of the IRS-1 protein. Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle.

Non-NASA Center↗

NASA NTRS2002

Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

Foton Project↗

NASA NTRS1997

Insulin attenuates atrophy of unweighted soleus muscle by amplified inhibition of protein degradation

Unweighting atrophy of immature soleus muscle occurs rapidly over the first several days, followed by slower atrophy coinciding with increased sensitivity to insulin of in vitro protein metabolism. This study determined whether this increased sensitivity might account for the diminution of atrophy after 3 days of tall-cast hindlimb suspension. The physiological significance of the increased response to insulin in unweighted muscle was evaluated by analyzing in vivo protein metabolism for day 3 (48 to 72 hours) and day 4 (72 to 96 hours) of unweighting in diabetic animals either injected with insulin or not treated. Soleus from nontreated diabetic animals showed a similar loss of protein during day 3 (-16.2%) and day 4 (-14.5%) of unweighting, whereas muscle from insulin-treated animals showed rapid atrophy (-14.5%) during day 3 only, declining to just -3.1% the next day. Since fractional protein synthesis was similar for both day 3 (8.6%/d) and day 4 (7.0%/d) of unweighting in insulin-treated animals, the reduction in protein loss must be accounted for by a slowing of protein degradation due to circulating insulin. Intramuscular (IM) injection of insulin (600 nmol/L) stimulated in situ protein synthesis similarly in 4-day unweighted (+56%) and weight-bearing (+90%) soleus, even though unweighted muscle showed a greater in situ response of 2-deoxy-[3H]glucose uptake to IM injection of either insulin (133 nmol/L) or insulin-like growth factor-I (IGF-I) (200 nmol/L) than control muscle. These findings suggest that unweighted muscle is selectively more responsive in vivo to insulin, and that the slower atrophy after 3 days of unweighting was due to an increased effect of insulin on inhibiting protein degradation.

NASA Discipline Musculoskeletal↗

NASA NTRS1994

Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading

Focal sarcomere disruptions were previously observed in adductor longus muscles of rats flown approximately two weeks aboard the Cosmos 1887 and 2044 biosatellite flights. These lesions, characterized by breakage and loss of myofilaments and Z-line streaming, resembled damage induced by unaccustomed exercise that includes eccentric contractions in which muscles lengthen as they develop tension. We hypothesized that sarcomere lesions in atrophied muscles of space flow rats were not produced in microgravity by muscle unloading but resulted from muscle reloading upon re-exposure to terrestrial gravity. To test this hypothesis, we examined temporal changes in sarcomere integrity of adductor longus muscles from rats subjected to 12.5 days of hindlimb suspension unloading and subsequent reloading by return to vivarium cages for 0, 6, 12, or 48 hours of normal weightbearing. Our ultrastructural observations suggested that muscle unloading (0 h reloading) induced myofibril misalignment associated with myofiber atrophy. Muscle reloading for 6 hours induced focal sarcomere lesions in which cross striations were abnormally widened. Such lesions were electron lucent due to extensive myofilament loss. Lesions in reloaded muscles showed rapid restructuring. By 12 hours of reloading, lesions were moderately stained foci and by 48 hours darkly stained foci in which the pattern of cross striations was indistinct at the light and electron microscopic levels. These lesions were spanned by Z-line-like electron dense filamentous material. Our findings suggest a new role for Z-line streaming in lesion restructuring: rather than an antecedent to damage, this type of Z-line streaming may be indicative of rapid, early sarcomere repair.

Non-NASA Center↗

NASA NTRS1992

Changes in skeletal muscle gene expression consequent to altered weight bearing

Skeletal muscle is a dynamic organ that adapts to alterations in weight bearing. This brief review examines changes in muscle gene expression resulting from the removal of weight bearing by hindlimb suspension and from increased weight bearing due to eccentric exercise. Acute (less than or equal to 2 days) non-weight bearing of adult rat soleus muscle alters only the translational control of muscle gene expression, while chronic (greater than or equal to 7 days) removal of weight bearing appears to influence pretranslational, translational, and posttranslational mechanisms of control. Acute and chronic eccentric exercise are associated with alterations of translational and posttranslational control, while chronic eccentric training also alters the pretranslational control of muscle gene expression. Thus alterations in weight bearing influence multiple sites of gene regulation.

NASA Discipline Musculoskeletal↗

NASA NTRS2011

Contribution of Spaceflight Environmental Factors to Vision Risks

The risk of visual impairment and elevated intracranial pressure as a result of low-earth orbit microgravity exposure has directed our attention and research efforts to the eye. While the alterations observed in astronauts returning from long duration missions include vision and neuroanatomical changes observed by non-invasive methods, other effects and subsequent tissue responses at the molecular and cellular level can only be studied by accessing the tissue itself. As a result of this need, several studies are currently taking place within the Human and Health Countermeasures Element (HHC) that use animal models for eye research. The rodent eye has many similarities to the human eye, and both rats and mice have historically been used as models of human eye disease, aiding in the identification of the disease genes, elucidation of mechanisms of disease, as well as in the assessment of therapeutic treatments. These studies attempt to answer two central questions in the etiology of possible vision alterations in the environment of space exploration missions. The first is: what effects and response mechanisms take place in the different eye structures at the cellular and molecular level? The second question is directed to elucidate the contribution of the various environmental stressors (radiation, nutrition, fluid shift) to these effects. Collaborative approaches with internal and external investigators have allowed performing these studies in a most cost-effective fashion, providing preliminary data and laying the bases for testing further hypotheses in future and specifically designed animal experiments. From a study centered on the radioadaptive response in mice, we have learned that the retina responds to low and high dose gamma radiation by elevating antioxidant-related genes at early time points (4hrs) and that this response returns to control levels after 1 day post-irradiation. We are expanding this research with another collaborative study that investigates the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in rat eyes. All main eye structures will be analyzed in this study: retina, lens and cornea. A study in collaboration with the Space Human Factors and Habitability Element (SHFH) investigates the effects of lunar dust exposure on the rat cornea. It is anticipated that common underlying oxidative stress mechanisms of damage may be observed as a result of these three stressors: radiation, nutritional iron and lunar dust. The contribution of fluid shift is addressed by a study using rats subjected to hindlimb suspension. The hypothesis to be tested in this study is that the mechanical stress imparted by the pressure differential across the optic disc and lamina cribosa will impact oxygenation (therefore causing oxidative stress and hypoxia) and cell survival. This study also includes the assessment of two nutritional antioxidant countermeasures: epigallocatechin gallate (green tea) and resveratrol. Finally, as a result of two successful tissue sharing efforts, we are proceeding with the analysis of eye samples of mice aboard two shuttle missions: STS-133 and STS-135. Results from the STS-133 study are presented in an independent abstract. Briefly, the results show that spaceflight represents a source of environmental stress that directly translates into oxidative and cellular stress in the retina. Similar analysis is also planned for the cornea. These samples add large value to our current vision research as they provide data on the direct effects of low-earth orbit spaceflight on eye structures and physiology.

Zanello, Susana B.↗

NASA NTRS2012

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↗

NASA NTRS2014

NASA HRP Immunology Discipline - Use of Terrestrial Analogs

Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune dysregulation, terrestrial immune analogs, and recent analog investigations.

Crucian, Brian↗

NASA NTRS2020

Circulating miRNA Signature Predicts Health Risks Associated with Cancer and Spaceflight

Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach, our previous NASA work has shown both TGF signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We are investigating this hypothesis with both in vivo and in vitro models to test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach is utilized to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR), we used ions, energy, and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To similate high-dose radiation exposure due to solar particle events (SPE), we used a solar particle event (SPE) sim model which gave a total dose of 1Gy protons with energy ranges from 50MeV to 150MeV. C57BL/6 wild-type female mice were utilized for the irradiations with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions was also irradiated. To expand on the circulating miRNA signature determined from our preliminary data, we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing was done on serum (at time of sacrifice), liver, heart, and muscle (soleus muscle) tissue for all radiation groups. Additional validation of the key miRNAs was performed by droplet digital PCR (ddPCR). This revealed a key circulating miRNA signature (consisting of multiple miRNAs) impacting cardiovascular and muscular disease risk. Further in vitro experiments with CRISPR/Cas9 system to knockout the key miRNA signatures, novel self-delivering antagomirs, overexpression of the miRNAs test the functional impact of the miRNA signatures on both microvascular disease and muscle degeneration due to space irradiation. The current work has started to allow the possible development of a novel minimally invasive miRNA based radioprotector to be used as a countermeasure for space radiation. Collectively, understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation. This work is supported by the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to AB.

Beheshti, Afshin↗

NASA NTRSDate not supplied

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended Rats

INTRODUCTION: The Spaceflight Associated Neuro-ocular Syndrome (SANS) is thought to be associated with weightlessness-induced cephalad fluid shift, possibly associated with a chronic elevation of intracranial pressure (ICP) during long-duration ISS missions. Changes in cerebrospinal fluid (CSF) dynamics and cranial compliance might be involved in the ICP increase. It is not known whether CSF production and/or outflow are altered in microgravity, but changes at the molecular and cellular level in the structures that produce and regulate the transcellular and paracellular secretion and reabsorption of CSF may be relevant. In this study, we used the rat hindlimb suspension (HS) model to examine the relationship between intracranial pressure (ICP) and the cellular responses to the prolonged change in body posture elicited specifically in the choroid plexus (CP). This was evaluated by transcriptomics, histopathology and ultrastructure of the CP and arachnoid villi (AV). METHODS: ICP was measured by telemetry. The morphology, ultrastructure, and gene expression profile of the CP was examined using male 9-month-old Long Evans rats subjected to HS for 14 and 90 days. A subset of animals completing 90-day HS returned to normal posture for 14 and 90 additional days of recovery. All HS rats had age-matched cage controls maintained in normal posture. A group of animals was maintained in conditions of 1% CO2 throughout the entire protocol. The rat brains were carefully removed and preserved for various analyses, including transmission electron microscopy (TEM), immunohistochemical analysis of specific targets involved in CSF regulation, and RNA sequencing analysis of laser capture micro-dissected CP tissue from the lateral ventricles. SUMMARY OF RESULTS: The ICP record was limited, which impacted any conclusions derived from the results. However, the ICP of rats in the CO2-enriched atmosphere appeared increased compared to those in a normal air composition. HS of rats resulted in an altered transcriptomics profile in the choroid plexus compared to animals maintained at normal posture. This was observed during both the HS period and during normal posture recovery period following 90 days of suspension. The greatest number of differentially expressed genes was observed at 90 days HS. Elevated CO2 also led to a different transcriptomics profile in the CP. The histology and ultrastructure results should be considered preliminary due to the limited number of samples. Examination of the CP by TEM showed blood vessel congestion and microvilli swelling in the CP, as well as some subpial and periventricular gliosis, but no associations were observed with treatment. There was no evidence of a reduced clearance of b-amyloid in the periventricular, perivascular and subpial regions of the brain in HS animals versus those in normal posture. Immunohistochemical staining of aquaporin 4, showed the localization to the subpial region and ependyma with increased immunoreactivity in the brains of CO2 exposed rats. This work was supported by awards NNX15AW48G to S.Z. Animal tissue and live data was provided under a tissue/data sharing agreement with Dr. Charles Fuller, UC Davis.

S B Zanello↗

NASA NTRSDate not supplied

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended RATS

S B Zanello↗

NASA NTRS1990

Age effects on rat hindlimb muscle atrophy during suspension unloading

The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

Steffen, Joseph M.↗

NASA NTRS1996

Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension

The present study was aimed at evaluating quantitatively gamma-aminobutyric acid (GABA) immunoreactivity in the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension. A reduction in the number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-containing terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system of hindlimb-suspended animals, it is suggested that the unloading due to hindlimb suspension alters afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the reduction in immunoreactivity of local circuit GABAergic neurons and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Non-NASA Center↗

NASA NTRS1983

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Musacchia, X. J.↗

NASA NTRS1993

Muscle glucose uptake in the rat after suspension with single hindlimb weight bearing

An examination is conducted of the effect of nonweight-bearing conditions, and the systemic influences of simulated microgravity on rat hindlimb muscles. The results obtained suggest that the increases in hindlimb muscle glucose uptake and extracellular space associated with simulated microgravity persist with hindlimb weightbearing, despite the prevention of muscle atrophy. The mechanism (or mechanisms) responsible for these effects are currently unknown.

Stump, Craig S.↗

NASA NTRS1982

Effect of suspension hypokinesia/hypodynamia on glucocorticoid receptor levels in rat hindlimb muscles

Ilyina-Kakueva et. al. (1976) conducted an investigation in which rats were exposed to weightlessness during the Cosmos program. An examination of the rats revealed a marked atrophy of hindlimb muscles. A suspension model has been developed to simulate these weightlessness-induced alterations. In agreement with the Cosmos studies, suspension hypokinesia/hypodynamia (H/H) results in differential atrophy of hindlimb muscles in rats. Recent studies have demonstrated elevated glucocorticoid receptor numbers in the gastrocnemius muscle following immobilization and denervation. One of the objectives of the present investigation was to evaluate the effect of suspension H/H on glucocorticoid receptor levels in rat hindlimb muscles. Another objective was to ascertain whether altered receptor levels reflect the differential nature of hindlimb muscle atrophy during suspension H/H. The obtained findings suggest that differential muscle atrophy resulting from H/H may result from differential alterations of glucocorticoid receptor levels.

Steffen, J. M.↗

NASA NTRS1994

Contribution of dietary and loading changes to the effects of suspension on mouse femora

The present study assessed the contributions of feeding changes and unloading to the overall measured effects of 2-wk hindlimb (Tail) suspension on the mouse femora. Feeding changes were addressed by considering the effects of matched feeding among suspended and control mice. The effects of hind limb unloading were considered by comparing suspended mice to mice equipped identically (though not suspended) and matched-fed. The feeding and unloading aspects of suspension appear to cause distinctly differing effects on the stereotypic modeling of the femora. Matched-feeding was accompanied by increased resorption surface in comparison to suspended mice, while unloading led to reduced bone formation at the mid-diaphysis of the femora. Reduced mineral content was observed in the bones of suspended mice when compared to the other mice groups, but without increased resorption surface. Thus, the unloading aspects of the antiorthostatic suspension protocol apparently causes reduced formation and mineralization in the femur.

Non-NASA Center↗

NASA NTRS2001

The Spacelab 3 simulation: basis for a model of growth plate response in microgravity in the rat

Data from Spacelab 3 (SL3) suggested that spaceflight significantly reduces the activity of the rat tibial growth plate. Animal processing after SL3 began twelve hours post-landing, so data reflect post-flight re-adaptation in addition to spaceflight effects. To determine if a twelve-hour period of weight bearing after seven days of unloading could affect the physes of spaceflown rats, the present study assessed the growth plate response to unloading with or without a reloading period. Rats were subjected to hind-limb suspension for seven days and then euthanized, with or without twelve hours of reloading. Activity of the growth plate was assessed by morphometric analysis. Rats suspended without reloading had reserve zone (RZ) height greater than controls, and shorter hypertrophy/calcification zone (HCZ) with fewer cells. The greater RZ was associated with a larger cell area, indicating a possible mitotic delay or secretion defect. Twelve hours of reloading decreased RZ height and cell number, and restored the number of cells in HCZ to control values, but the number of cells in the proliferative zone and height in HCZ were reduced. These results suggest the rebound response to preserve/restore skeletal function after a period of unloading involves an acceleration of growth associated with a decreased cell cycle time in PZ. Changes during the reloading period in this simulation support our hypothesis that the effects of spaceflight on SL3 growth plates were altered by changes that occurred post-landing. The similarities in response to unloading by suspension or during spaceflight are used to propose a model of growth plate response during spaceflight.

manned↗