We developed a new model of hypodynamic loading to support mice in chronic conditions of partial weight bearing, enabling simulations of reduced gravity environments and related clinical conditions. The novel hardware allows for reduced loading between 10 and 80% of normal body weight on all four limbs and enables characteristic quadrupedal locomotion. Ten-week-old female BALB/cByJ mice were supported for 21 days under Mars-analog suspension (38% weight bearing) and compared with age-matched and jacketed (100% weight bearing) controls. After an initial adaptation, weight gain did not differ between groups, suggesting low levels of animal stress. Relative to age-matched controls, mice exposed to Mars-analog loading had significantly lower muscle mass (-23% gastrocnemius wet mass, P < 0.0001); trabecular and cortical bone morphology (i.e., trabecular bone volume: -24% at the distal femur, and cortical thickness: -11% at the femoral midshaft, both P < 0.001); and biomechanical properties of the femoral midshaft (i.e., -27% ultimate moment, P < 0.001). Bone formation indexes were decreased compared with age-matched full-weight-bearing mice, whereas resorption parameters were largely unchanged. Singly housed, full-weight-bearing controls with forelimb jackets were largely similar to age-matched, group-housed controls, although a few variables differed and warrant further investigation. Altogether, these data provide strong rationale for use of our new model of partial weight bearing to further explore the musculoskeletal response to reduced loading environments.

Animal models are frequently used to assist in the determination of the long- and short-term effects of space flight. The space environment, including microgravity, can impact many physiological and immunological system parameters. It has been found that ground based models of microgravity produce changes in white blood cell counts, which negatively affects immunologic function. As part of the Center of Acute Radiation Research (CARR), we compared the acute effects on white blood cell parameters induced by the more traditionally used animal model of hindlimb unloading (HU) with a recently developed reduced weightbearing analog known as partial weight suspension (PWS). Female ICR mice were either hindlimb unloaded or placed in the PWS system at 16% quadrupedal weightbearing for 4 h, 1, 2, 7 or 10 days, at which point complete blood counts were obtained. Control animals (jacketed and non-jacketed) were exposed to identical conditions without reduced weightbearing. Results indicate that significant changes in total white blood cell (WBC), neutrophil, lymphocyte, monocyte and eosinophil counts were observed within the first 2 days of exposure to each system. These differences in blood cell counts normalized by day 7 in both systems. The results of these studies indicate that there are some statistically significant changes observed in the blood cell counts for animals exposed to both the PWS and HU simulated microgravity systems.

Purpose The effects of radiation +/− hypogravity on immunologic function were investigated using the Partial Weight Suspension (PWS) model (Wagner et al. 2010). Materials and methods Mice were exposed to 0.5, 1, or 2 Gray (Gy) dose of gamma radiation and then placed in the PWS system for 4, 24, 48 hours, or 4 days. Spleens were excised and white blood cells were prepared for flow cytometry analyses. Results The combination of PWS + radiation (1 and 2 Gy doses only) resulted in decreased cell viability at the 24 h (~16% decrease), 48 h (~20% decrease), and 4 day (~20% decrease) time points, compared to the PWS (no radiation) and no treatment (non-suspended, non-irradiated) groups. The T lymphocyte (thymus-derived) population increased by ~10% (24 h, 48 h, and 4 day time points), while the B lymphocyte (bursal or bone marrow-derived) population decreased by ~10% (at all time points examined), when mice were exposed to PWS + radiation (2 Gy dose only), compared to the PWS or no treatment groups. T cell activation was observed in the PWS group and the 0.5 Gy +/− PWS groups at the 4 and 24 h time points, compared to the no treatment group. However, T cell activation was significantly suppressed (~85%) at the acute time points in the 2 Gy +/− PWS groups, comparable to the no treatment group. Conclusions Ionizing radiation in the absence and presence of simulated hypogravity results in acute lymphocyte dysfunction and compromised immune response.

No abstract