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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.

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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Early Unloading After ACL Rupture and Prior to Surgical Restabilization in Mice Slows Post-Traumatic Osteoarthritis Progression

Purpose: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often go on to develop post-traumatic osteoarthritis (PTOA). ACL injuries are often treated with ACL reconstruction, but there is typically a gap of several weeks between injury and surgery. However, it is unclear how loading or unloading of the injured joint during the early postinjury period affects the progression of PTOA. The goal of this study was to determine how unloading between noninvasive ACL injury and surgical restabilization of the injured joint affects PTOA progression in mice. Findings: Mice were subjected to noninvasive ACL injury or no injury followed by 1 week of hindlimb unloading (HLU) or normal cage activity. After 1 week of HLU or cage activity, mice underwent restabilization surgery or no surgery. ACL injury resulted in considerable epiphyseal trabecular bone loss regardless of HLU or cage activity. HLU groups exhibited significantly reduced chondrophyte/osteophyte formation, OA scoring, and synovitis at day 42. Single-cell RNA sequencing revealed that 1 week of HLU resulted in more neutrophils and less monocytes-macrophages in the injured joint. Conclusions: This study establishes that 1 week of HLU after ACL injury effectively slowed PTOA progression, suggesting that the early inflammatory response and joint instability play a key role in PTOA initiation and progression, and neutrophils and monocytes-macrophages play roles in the modulation. However, subsequent joint restabilization surgery caused greater inflammatory protease activity in the joint and exacerbated the loss of epiphyseal trabecular bone but did not significantly diminish OA score or synovitis.

ACL injury↗
NASA NTRS2017

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↗
DOE OSTI2018

Autophagy activation facilitates mechanical stimulation-promoted osteoblast differentiation and ameliorates hindlimb unloading-induced bone loss

Highlights: • Autophagy is activated during mechanical stretching facilitated osteoblast differentiation of BMSCs. • Autophagy activation is essential for mechanical stretching promoted osteoblast differentiation of BMSCs. • Autophagy activation ameliorates hindlimb unloading-induced bone loss by enhancing osteoblast differentiation. Autophagy has been indicated to be involved in regulating bone metabolism. However, little is known about the role of autophagy in mechanical stimulation-influenced osteoblast differentiation and bone formation. In the present study, we first demonstrated that autophagy activation was essential for cyclic mechanical stretching-promoted osteoblast differentiation of bone marrow mesenchymal stem cells. To explore the in vivo role of autophagy in osteoblast differentiation, the hindlimb unloading-induced disuse osteoporosis model was used. Compared to the normal controls, hindlimb unloading led to abundant bone loss as well as lessened autophagy activation of osteoblasts. However, the activation of autophagy by ULK1 overexpression or in the presence of rapamycin significantly increased osteoblast differentiation activity and restored the bone volume. The findings implicate autophagy as a novel mechanosensitive pathway that regulates osteoblast differentiation. The pharmacological activation of autophagy may be an interesting approach for the prevention and treatment of disuse osteoporosis.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1969

Bootstrap unloader

Circuit can sample a number of transducers in sequence without drawing from them. This bootstrap unloader uses a differential amplifier with one input connected to a circuit which is the equivalent of the circuit to be unloaded, and the other input delivering the proper unloading currents.

Pfiffner, H. J.↗
NASA NTRS1977

Acoustic emission during unloading of elastically stressed magnesium alloy

A magnesium alloy was quasi-statically cycled elastically between zero load and tension. Both loading and unloading stress delays were found, and the unloading stress delay was further studied. An analytical expression was written for the unloading stress delay which is an elastic constitutive parameter. The potential use of these results for the acoustic emission monitoring of elastic stress states is discussed.

Lee, S. S.↗
NASA NTRS1985

Muscle protein and glycogen responses to recovery from hypogravity and unloading by tail-cast suspension

Previous studies in this laboratory using the tail-bast hindlimb suspension model have shown that there are specific changes in protein and carbohydrate metabolism in the soleus muscle due to unloading. For example, 6 days of unloading caused a 27% decrease in mass and a 60% increase in glycogen content in the soleus muscle, while the extensor digitorum longus muscle was unaffected. Also, fresh tissue tyrosine and its in vitro release from the muscle are increased in the unloaded soleus, indicating that this condition causes a more negative protein balance. With these results in mind, studies to investigate the effect of hypogravity on protein and carbohydrate metabolism in a number of rat hindlimb muscles were carried out.

Henriksen, E. J.↗
NASA NTRS1984

The temporal response of bone to unloading

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Globus, R. K.↗
NASA NTRS1985

Biochemical response to chronic shortening in unloaded soleus muscles

One leg of tail-casted suspended rats was immobilized in a plantar-flexed position to test whether chronic shortening of posterior leg muscles affected the metabolic response to unloading. The immobilized plantaris and gastrocnemius muscles of these animals showed approximately 20 percent loss of muscle mass in contrast to simply a slower growth rate with unloading. Loss of mass of the soleus muscle during suspension was not accentuated by chronic shortening. Although protein degradation in the isolated soleus muscle of the plantar-flexed limb was slightly faster than in the contralateral free limb, this difference was offset by faster synthesis of the myofibrillar protein fraction of the chronically shortened muscle. Total adenine nucleotides were 17 percent lower (P less than 0.005) in the chronically shortened soleus muscle following incubation. Glutamate, glutamine, and alanine metabolism showed little response to chronic shortening. These results suggest that, in the soleus muscle, chronic shortening did not alter significantly the metabolic responses to unloading and reduced activity.

Jaspers, S. R.↗
NASA NTRS1985

Muscle protein and glycogen responses to recovery from hypogravity and unloading by tail-cast suspension

Previous studies in this laboratory using the tail-bast hindlimb suspension model have shown that there are specific changes in protein and carbohydrate metabolism in the soleus muscle due to unloading. For example, 6 days of unloading caused a 27 percent decrease in mass and a 60 percent increse in glycogen content in the soleus muscle, while the extensor digitorum longus muscle was unaffected. Also, fresh tissue tyrosine and its in vitro release from the muscle are increased in the unloaded soleus, indicating that this condition causes a more negative protein balance. With these results in mind, studies to investigate the effect of hypogravity on protein and carbohydrate metabolism in a number of rat hindlimb muscles were carried out.

Henriksen, E. J.↗
NASA NTRS1991

Project UM-HAUL: A self-unloading reusable lunar lander

The establishment of a lunar base is technologically and financially challenging. Given the necessary resources and political support, it can be done. In addition to the geopolitical obstacles, however, there are logistical problems involved in establishing such bases that can only be overcome with the acquisition of a significant transportation and communications network in the Earth-Moon spatial region. Considering the significant number of payloads that will be required in this process, the mass-specific cost of launching these payloads, and the added risk and cost of human presence in space, it is clearly desirable to automate major parts of such an operation. One very costly and time-consuming factor in this picture is the delivery of payloads to the Moon. Foreseeable payloads would include atmospheric modules, inflatable habitat kits, energy and oxygen plant elements, ground vehicles, laboratory modules, crew supplies, etc. The duration of high-risk human presence on the Moon could be greatly reduced if all such payloads were delivered to the prospective base site in advance of crew arrival. In this view, the idea of a 'Self-Unloading Reusable Lunar Lander' (SURLL) arises naturally. The general scenario depicts the lander being brought to low lunar orbit (LLO) from Earth atop a generic Orbital Transfer Vehicle (OTV). From LLO, the lander shuttles payloads down to the lunar surface, where, by means of some resident, detachable unloading device, it deploys the payloads and returns to orbit. The general goal is for the system to perform with maximum payload capability, automation, and reliability, while also minimizing environmental hazards, servicing needs, and mission costs. Our response to this demand is UM-HAUL, or the UnManned Heavy pAyload Unloader and Lander. The complete study includes a system description, along with a preliminary cost analysis and a design status assessment.

Source record↗
NASA NTRS1992

Skeletal muscle responses to unloading with special reference to man

The limited space flight data suggest that exposure to microgravity decreases muscle strength in humans and muscle mass in lower mammals. Several earth-based models have been used to address the effect of unloading on the human neuromuscular system due to the limited access of biological research to long-term space flight. Bedrest eliminates body weight bearing of both lower limbs. Unilateral lower limb suspension (ULLS), where all ambulatory activity is performed on crutches with an elevated sole on the shoe of one foot, has recently been used to unload one lower limb. The results from studies using these two models support their efficacy. The decrease in strength of m. quadriceps femoris, for example, after four to six weeks of bedrest, ULLS or space flight is 20 to 25 percent. The results from the earth-based studies show that this response can be attributed in part to a decrease in the cross-sectional area of the KE which reflects muscle fiber atrophy. The results from the ground based studies also support the limited flight data and show that reductions in strength are larger in lower than upper limbs and in extensor than flexor muscle groups. They also raise issue with the generally held concept that postural muscle is most affected by unweighting. Slow-twitch fibers in lower limb muscles of mixed fiber type composition and muscle composed mainly of slow-twitch fibers do not preferentially atrophy after bedrest or ULLS. Taken together, the data suggest that unloading causes remarkable adaptations in the neuromuscular system of humans. It should be appreciated, however, that this area of research is in its infancy.

Dudley, G. A.↗
NASA NTRS1992

Skeletal muscle responses to unloading in humans

This study examined the effects of unloading on skeletal muscle structure. Method: Eight subjects walked on crutches for six weeks with a 110 cm elevated sole on the right shoe. This removed weight bearing by the left lower limb. Magnetic resonance imaging of both lower limbs and biopsies of the left m. vastus laterallis (VL) were used to study muscle structure. Results: Unloading decreased (P less than 0.05) muscle cross-sectional areas (CSA) of the knee extensors 16 percent. The knee flexors showed about 1/2 of this response (-7 percent, P less than 0.05). The three vasti muscles each showed decreases (P less than 0.05) of about 15 percent. M. rectus femoris did not change. Mean fiber CSA in VL decreased (P less than 0.05) 14 percent with type 2 and type 1 fibers showing reductions of 15 and 11 percent respectively. The ankle extensors showed a 20 percent decrease (P less than 0.05) in CSA. The reduction for the 'fast' m. gastrocnemius was 27 percent compared to the 18 percent decrease for the 'slow' soleus. Summary: The results suggest that decreases in muscle CSA are determined by the relative change in impact loading history because atrophy was (1) greater in extensor than flexor muscles, (2) at least as great in fast as compared to slow muscles or fibers, and (3) not dependent on single or multi-joint function. They also suggest that the atrophic responses to unloading reported for lower mammals are quantitatively but not qualitatively similar to those of humans.

Dudley, G.↗
NASA NTRS1992

Driven and unloading aspects of magnetospheric substorms

Issues concerning the 'driven' versus 'unloading' nature of substorms are presented. The original concepts attendant to this debate are presented and substorms are concluded to inextricably combine aspects that are driven with aspects that represent a loading-unloading system. For isolated substorms, the magnetosphere-ionosphere system is shown to exhibit a bimodal response to solar wind changes. A 20 min response characteristic is associated with the driven aspect of substorms, while a 1 hr response time is associated with unloading. It is found that for strong solar wind input conditions, the magnetospheric response becomes more nearly unimodal. This is interpreted in terms of a nonlinear dynamical evolution of the system. Simple analog models are described which capture the essence of the nonlinear magnetospheric behavior. These models exhibit chaotic transitions for strong driving conditions: this may explain the observed behavior of the magnetosphere during strong geomagnetic activity.

Baker, D. N.↗
NASA NTRS1994

Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

Arnnaud, Sara B.↗
NASA NTRS2003

The impact of skeletal unloading on bone formation

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

NASA Discipline Musculoskeletal↗
NASA NTRS2002

Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats

Attenuated baroreflex-mediated increases in renal sympathetic nerve activity (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition of the rostral ventrolateral medulla (RVLM) is increased after hindlimb unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)-bicuculline methiodide (BIC) into the RVLM were examined before and during caudal ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in response to BIC in the RVLM were significantly enhanced in HU rats. Responses to bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in the RVLM was blocked by BIC during CVLM inhibition, the additional increases in MAP and RSNA were significantly greater in HU rats. These data indicate that GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb unloading. Effects of input from the CVLM were unaltered. Thus, after cardiovascular deconditioning in rodents, the attenuated increase in sympathetic nerve activity in response to hypotension is associated with greater GABA(A) receptor-mediated inhibition of RVLM neurons originating at least in part from sources other than the CVLM.

Non-NASA Center↗
NASA NTRS1998

Nerve-responsive troponin I slow promoter does not respond to unloading

We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the -4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice ( approximately 30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls (n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (-6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (-25%) and soleus mass relative to body mass (-16%) were both lower (P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease (P < 0.05) in the abundance of endogenous TnIs mRNA (microg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference (P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.

Non-NASA Center↗
NASA NTRS1992

Vasopressin responses to unloading arterial baroreceptors during cardiac nerve blockade in conscious dogs

We examined the relative contributions of afferent input from the heart and from arterial baroreceptors in the stimulation of arginine vasopressin (AVP) secretion in response to hypotension caused by thoracic inferior vena caval constriction (TIVCC). Afferent input from cardiac receptors was reversibly blocked by infusing 2% procaine into the pericardial space to anesthetize the cardiac nerves. Acute cardiac nerve blockade (CNB) alone caused a rise in mean arterial pressure (MAP) of 24 +/- 3 mmHg but no change in plasma AVP. If the rise in MAP was prevented by TIVCC, plasma AVP increased by 39 +/- 15 pg/ml, and if MAP was allowed to increase and then was forced back to control by TIVCC, plasma AVP increased by 34 +/- 15 pg/ml. Thus the rise in MAP during CNB stimulated arterial baroreceptors, which in turn compensated for the loss of inhibitory input from cardiac receptors on AVP secretion. These results indicate that the maximum secretory response resulting from complete unloading of cardiac receptors at a normal MAP results in a mean increase in plasma AVP of 39 pg/ml in this group of dogs. When MAP was reduced 25% below control levels (from 95 +/- 5 to 69 +/- 3 mmHg) by TIVCC during pericardial saline infusion, plasma AVP increased by 79 +/- 42 pg/ml. However, the same degree of hypotension during CNB (MAP was reduced from 120 +/- 5 to 71 +/- 3 mmHg) led to a greater (P less than 0.05) increase in plasma AVP of 130 +/- 33 pg/ml. Because completely unloading cardiac receptors can account for an increase of only 39 pg/ml on average in this group of dogs, the remainder of the increase in plasma AVP must be due to other sources of stimulation. We suggest that the principal stimulus to AVP secretion after acute CNB in these studies arises from unloading the arterial baroreceptors.

NASA Center ARC↗