| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Life Sciences Division, NASA Ames Research Center, Moffett Field, California 94035-1000
Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30° head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.
simulated weightlessness; hindlimb suspension; altered gravity; mechanical load; animal model
This article has been cited by other articles:
|
|
 |
|
  P. M. Siu, E. E. Pistilli, and S. E. Alway Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading J Appl Physiol, December 1, 2008; 105(6): 1695 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dumont, P. Bouchard, and J. Frenette Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1831 - R1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Widrick, G. F. Maddalozzo, H. Hu, J. C. Herron, U. T. Iwaniec, and R. T. Turner Detrimental effects of reloading recovery on force, shortening velocity, and power of soleus muscles from hindlimb-unloaded rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1585 - R1592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-F. Zhang, J.-H. Cheng, X. Liu, S. Wang, Y. Liu, H.-B. Lu, and J. Ma Cardiovascular changes of conscious rats after simulated microgravity with and without daily -Gx gravitation J Appl Physiol, October 1, 2008; 105(4): 1134 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mueller Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R727 - R732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Yin, J.-C. Liu, R. Fan, X.-Q. Sun, J. Ma, N. Feng, Q. Y. Zhang, Z. Yin, S.-M. Zhang, H.-T. Guo, et al. Modulation of {beta}-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats J Appl Physiol, August 1, 2008; 105(2): 569 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y-I. Ju, T. Sone, T. Okamoto, and M. Fukunaga Jump exercise during remobilization restores integrity of the trabecular architecture after tail suspension in young rats J Appl Physiol, June 1, 2008; 104(6): 1594 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gundersen and J. C. Bruusgaard Nuclear domains during muscle atrophy: nuclei lost or paradigm lost? J. Physiol., June 1, 2008; 586(11): 2675 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Radek, L. A. Baer, J. Eckhardt, L. A. DiPietro, and C. E. Wade Mechanical unloading impairs keratinocyte migration and angiogenesis during cutaneous wound healing J Appl Physiol, May 1, 2008; 104(5): 1295 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Martinez, A. C. Vailas, R. Vanderby Jr., and R. E. Grindeland Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1552 - R1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dumont, K. Lepage, C. H. Cote, and J. Frenette Mast cells can modulate leukocyte accumulation and skeletal muscle function following hindlimb unloading J Appl Physiol, July 1, 2007; 103(1): 97 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Xue, L.-F. Zhang, J. Ma, and M.-J. Xie Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H691 - H701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Lintault, E. I. Zakrzewska, R. L. Maple, L. A. Baer, T. M. Casey, A. E. Ronca, C. E. Wade, and K. Plaut In a hypergravity environment neonatal survival is adversely affected by alterations in dam tissue metabolism rather than reduced food intake J Appl Physiol, June 1, 2007; 102(6): 2186 - 2193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hwang, S. A. Shelkovnikov, and R. E. Purdy Simulated microgravity effects on the rat carotid and femoral arteries: role of contractile protein expression and mechanical properties of the vessel wall J Appl Physiol, April 1, 2007; 102(4): 1595 - 1603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Pistilli, P. M. Siu, and S. E. Alway Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1298 - C1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Tuday, J. V. Meck, D. Nyhan, A. A. Shoukas, and D. E. Berkowitz Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance J Appl Physiol, March 1, 2007; 102(3): 853 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Tidball and M. Wehling-Henricks Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo J. Physiol., January 1, 2007; 578(1): 327 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Turner, S. Lotinun, T. E. Hefferan, and E. Morey-Holton Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone J Appl Physiol, September 1, 2006; 101(3): 881 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mueller, M. J. Sullivan, R. R. Grindstaff, J. T. Cunningham, and E. M. Hasser Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R46 - R52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Siu, E. E. Pistilli, Z. Murlasits, and S. E. Alway Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats J Appl Physiol, March 1, 2006; 100(3): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sitnick, A. M. Foley, M. Brown, and E. E. Spangenburg Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass J Appl Physiol, January 1, 2006; 100(1): 286 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. De-Doncker, M. Kasri, F. Picquet, and M. Falempin Physiologically adaptive changes of the L5 afferent neurogram and of the rat soleus EMG activity during 14 days of hindlimb unloading and recovery J. Exp. Biol., December 15, 2005; 208(24): 4585 - 4592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Hilder, L. A. Baer, P. M. Fuller, C. A. Fuller, R. E. Grindeland, C. E. Wade, and L. M. Graves Insulin-independent pathways mediating glucose uptake in hindlimb-suspended skeletal muscle J Appl Physiol, December 1, 2005; 99(6): 2181 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Krawiec, R. A. Frost, T. C. Vary, L. S. Jefferson, and C. H. Lang Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesis Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E969 - E980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cormery, E. Beaumont, K. Csukly, and P. Gardiner Hindlimb unweighting for 2 weeks alters physiological properties of rat hindlimb motoneurones J. Physiol., November 1, 2005; 568(3): 841 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Foley, P. J. Mueller, E. M. Hasser, and C. M. Heesch Hindlimb unloading and female gender attenuate baroreflex-mediated sympathoexcitation Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1440 - R1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Siu, E. E. Pistilli, and S. E. Alway Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R1015 - R1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-J. Xie, L.-F. Zhang, J. Ma, and H.-W. Cheng Functional alterations in cerebrovascular K+ and Ca2+ channels are comparable between simulated microgravity rat and SHR Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1265 - H1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kyparos, D. L. Feeback, C. S. Layne, D. A. Martinez, and M. S. F. Clarke Mechanical stimulation of the plantar foot surface attenuates soleus muscle atrophy induced by hindlimb unloading in rats J Appl Physiol, August 1, 2005; 99(2): 739 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yimlamai, S. L. Dodd, S. E. Borst, and S. Park Clenbuterol induces muscle-specific attenuation of atrophy through effects on the ubiquitin-proteasome pathway J Appl Physiol, July 1, 2005; 99(1): 71 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fluck, S. Schmutz, M. Wittwer, H. Hoppeler, and D. Desplanches Transcriptional reprogramming during reloading of atrophied rat soleus muscle Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R4 - R14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Stein and C. E. Wade Metabolic Consequences of Muscle Disuse Atrophy J. Nutr., July 1, 2005; 135(7): 1824S - 1828S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mueller, C. M. Foley, and E. M. Hasser Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R140 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. X. Nguyen, A. J. Lusis, and J. G. Tidball Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo J. Physiol., June 1, 2005; 565(2): 403 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. T. Iwaniec, T. J. Wronski, D. Amblard, Y. Nishimura, M. C. H. van der Meulen, C. E. Wade, M. A. Bourgeois, C. D. Damsky, and R. K. Globus Effects of disrupted {beta}1-integrin function on the skeletal response to short-term hindlimb unloading in mice J Appl Physiol, February 1, 2005; 98(2): 690 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. L. Tou, S. B. Arnaud, R. Grindeland, and C. Wade The Effect of Purified Compared with Nonpurified Diet on Bone Changes Induced by Hindlimb Suspension of Female Rats Experimental Biology and Medicine, January 1, 2005; 230(1): 31 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Durham, Y.-P. Li, E. Gerken, M. Farid, S. Arbogast, R. R. Wolfe, and M. B. Reid Fatiguing exercise reduces DNA binding activity of NF-{kappa}B in skeletal muscle nuclei J Appl Physiol, November 1, 2004; 97(5): 1740 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Aviles, T. Belay, M. Vance, B. Sun, and G. Sonnenfeld Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions J Appl Physiol, October 1, 2004; 97(4): 1437 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-J. Fu, M.-J. Xie, L.-F. Zhang, H.-W. Cheng, and J. Ma Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1505 - H1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V. Baewer, M. Hoffman, J. G. Romatowski, J. L. W. Bain, R. H. Fitts, and D. A. Riley Passive stretch inhibits central corelike lesion formation in the soleus muscles of hindlimb-suspended unloaded rats J Appl Physiol, September 1, 2004; 97(3): 930 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sun, L.-F. Zhang, F. Gao, X.-W. Ma, M.-L. Zhang, J. Liu, L.-N. Zhang, and J. Ma Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats J Appl Physiol, September 1, 2004; 97(3): 1022 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Gallegly, N. A. Turesky, B. A. Strotman, C. M. Gurley, C. A. Peterson, and E. E. Dupont-Versteegden Satellite cell regulation of muscle mass is altered at old age J Appl Physiol, September 1, 2004; 97(3): 1082 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Sullivan, E. M. Hasser, J. A. Moffitt, S. B. Bruno, and J. T. Cunningham Rats exhibit aldosterone-dependent sodium appetite during 24 h hindlimb unloading J. Physiol., June 1, 2004; 557(2): 661 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. McClung, R. W. Thompson, L. L. Lowe, and J. A. Carson RhoA expression during recovery from skeletal muscle disuse J Appl Physiol, April 1, 2004; 96(4): 1341 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. L. Tou, R. E. Grindeland, and C. E. Wade Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E425 - E433. [Abstract] [Full Text]
|
|
|
|
|
|
T. E. Hefferan, G. L. Evans, S. Lotinun, M. Zhang, E. Morey-Holton, and R. T. Turner Effect of gender on bone turnover in adult rats during simulated weightlessness J Appl Physiol, November 1, 2003; 95(5): 1775 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frenette, N. Chbinou, C. Godbout, D. Marsolais, and P. S. Frenette Macrophages, not neutrophils, infiltrate skeletal muscle in mice deficient in P/E selectins after mechanical reloading Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R727 - R732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Aviles, T. Belay, K. Fountain, M. Vance, B. Sun, and G. Sonnenfeld Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions J Appl Physiol, August 1, 2003; 95(2): 491 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Casse, D. Desplanches, M. H. Mayet-Sornay, M. Raccurt, S. Jegou, and G. Morel Growth Hormone Receptor Expression in Atrophying Muscle Fibers of Rats Endocrinology, August 1, 2003; 144(8): 3692 - 3697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-F. Zhang, B. Sun, X.-S. Cao, C. Liu, Z.-B. Yu, L.-N. Zhang, J.-H. Cheng, Y.-H. Wu, and X.-Y. Wu Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity J Appl Physiol, July 1, 2003; 95(1): 207 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Aviles, T. Belay, K. Fountain, M. Vance, and G. Sonnenfeld Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions J Appl Physiol, July 1, 2003; 95(1): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mueller and E. M. Hasser Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb-unloaded rats J Appl Physiol, May 1, 2003; 94(5): 1806 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Allen and S. A. Bloomfield Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats J Appl Physiol, February 1, 2003; 94(2): 642 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tou, A. Ronca, R. Grindeland, and C. Wade Models to Study Gravitational Biology of Mammalian Reproduction Biol Reprod, December 1, 2002; 67(6): 1681 - 1687. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
