Comparison of hindlimb unloading and partial weight suspension models for spaceflight-type condition induced effects on white blood cells

Abstract

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.

Leukocyte Activity Is Altered in a Ground Based Murine Model of Microgravity and Proton Radiation Exposure

“…Previously, we have shown that blood cell counts vary within the first 48 hours of exposure to HU, after which time the counts are not different in a statistically significant manner, compared to the non-suspended controls. The changes in blood cell counts is presumably attributed to stress of the HU system [29]. To study an “acute” time point after radiation +/− HU treatment, a 4 day time point was chosen so that the initial stress response to the suspension system would be minimized.…”

Biological effects of space radiation and development of effective countermeasures

“…Thus, several experiments have been performed to determine the effects of simulated microgravity on blood cell counts with or without additional exposure to space radiation [e.g., (148)]. To evaluate the impact of hypogravity on the effect of SPE radiation on immunological function, experiments were performed with 6–8 week old female ICR mice that were irradiated with 0.5, 1 or 2 Gy of γ-rays with or without hypogravity simulated using the PWS model, described by Wagner et al (149).…”

“…Numerous studies have been performed to evaluate the effects of SPE radiation on the immune system as a part of research on the acute risks of SPE radiation exposure (138, 144,148, 151, 152). Many of the SPE radiation studies were performed with and without microgravity simulated with PWS or HS (134, 138,148, 151–153).…”

“…Many of the SPE radiation studies were performed with and without microgravity simulated with PWS or HS (134, 138,148, 151–153). For the studies related to immune system effects, mice were exposed to homogeneous doses of either γ-ray or SPE- like proton radiation.…”

Mechanism of hypocoagulability in proton-irradiated ferrets

“…Proposed manned-missions by the National Aeronautics Space Administration (NASA) to the surface of Mars have led to concerns about the effects of a three-year mission on astronaut health (Badhwar et al 1992), with the most serious concerns involving the potential biological consequences of exposure to space radiation and prolonged exposure to microgravity (Cucinotta et al 2001, Mognato et al 2009, Wilson et al 2012). On a mission to Mars, astronauts will be exposed to background levels of highly energetic, charged particles known as HZE particles and solar particle event (SPE) radiation (Hellweg and Baumstark-Khan 2007).…”