Evidence indicates that astronauts experience significant bone loss during space mission. Recently, we used the NASA developed rotary cell culture system (RCCS) to simulate microgravity (μXg) conditions and demonstrated increased osteoclastogenesis in mouse bone marrow cultures. Autophagy is a cellular recycling process of nutrients. Therefore, we hypothesize that μXg control of autophagy modulates osteoclastogenesis. Real-time PCR analysis of total RNA isolated from mouse bone marrow derived non-adherent cells subjected to modeled μXg showed a significant increase in autophagic marker Atg5, LC3 and Atg16L mRNA expression compared to ground based control (Xg) cultures. Western blot analysis of total cell lysates identified an 8.0-fold and 7.0-fold increase in the Atg5 and LC3-II expression, respectively. Confocal microscopy demonstrated an increased autophagosome formation in μXg subjected RAW 264.7 preosteoclast cells. RT2 profiler PCR array screening for autophagy related genes identified that μXg upregulates intracellular signaling molecules associated with autophagy, autophagosome components and inflammatory cytokines/growth factors which coregulate autophagy in RAW 264.7 preosteoclast cells. Autophagy inhibitor, 3-methyladenine (3-MA) treatment of mouse bone marrow derived non-adherent mononuclear cells showed a significant decrease in μXg induced Atg5 and LC3 mRNA expression in the presence or absence of RANK ligand (RANKL) stimulation. Furthermore, RANKL treatment significantly increased (8-fold) p-CREB transcription factor levels under μXg as compared to Xg cultures and 3-MA inhibited RANKL increased p-CREB expression in these cells. Also, 3-MA suppresses μXg elevated osteoclast differentiation in mouse bone marrow cultures. Thus, our results suggest that μXg induced autophagy plays an important role in enhanced osteoclast differentiation and could be a potential therapeutic target to prevent bone loss in astronauts during space flight missions.

We reviewed the relevant literature delineating advances in the development of the experimental models of repeated blast TBI (rbTBI). It appears this subject is a relatively unexplored area considering the first work published in 2007 and the bulk of peer-reviewed papers was published post-2011. There are merely 34 papers published to date utilizing rodent rbTBI models. We performed an analysis and extracted basic parameters to capture the characteristics of the exposure conditions (the blast intensity, inter-exposure interval and the number of exposures), the age and weight of the animal models most commonly used in the studies, and their endpoints. Our analysis revealed three strains of rodents are predominantly used: Sprague Dawley and Long Evans rats and wild type (C57BL/6J) mice, and young adult animals 8 to 12-week-old are a preferred choice. Typical exposure conditions are the following: (1) peak overpressure in the 27–145 kPa (4–21 psi) range, (2) number of exposures: 2 (13.9%), 3 (63.9%), 5 (16.7%), or 12 (5.6%) with a single exposure used for a baseline comparison in 41.24% of the studies. Two inter-exposure interval durations were used: (1) short (1–30 min.) and (2) extended (24 h) between consecutive shock wave exposures. The experiments included characterization of repeated blast exposure effects on auditory, ocular and neurological function, with a focus on brain etiology in most of the published work. We present an overview of major histopathological findings, which are supplemented by studies implementing MRI (DTI) and behavioral changes after rbTBI in the acute (1–7 days post-injury), subacute (7–14 days), and chronic (>14 days) phases post-injury.

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Experimental data and finite element simulations of an anthropometric surrogate headform was used to evaluate the effect of specimen location and orientation on surface pressures following shock exposures of varying intensity. It was found that surface pressure distributions changed with local flow field disturbances, making it necessary to use data reduction strategies to facilitate comparisons between test locations, shock wave intensities and headform orientations. Non-dimensional parameters, termed amplification factors, were developed to permit direct comparisons of pressure waveform characteristics between incident shock waves differing in intensity, irrespective of headform location and orientation. This approach proved to be a sensitive metric, highlighting the flow field disturbances which exist in different locations and indicating how geometric factors strongly influence the flow field and surface pressure distribution.

Compressed gas-driven shock tubes are widely used for laboratory simulation of primary blasts by accurately replicating pressure profiles measured in live-fire explosions. These investigations require sound characterization of the primary blast wave, including the temporal and spatial evolution of the static and dynamic components of the blast wave. The goal of this work is to characterize the propagation of shock waves in and around the exit of a shock tube via analysis of the primary shock flow, including shock wave propagation and decay of the shock front, and secondary flow phenomena. To this end, a nine-inch shock tube and a cylindrical sensing apparatus were used to determine incident and total pressures outside of the shock tube, highlighting the presence of additional flow phenomena. Blast overpressure, impulse, shock wave arrival times, positive phase duration, and shock wave planarity were examined using a finite element model of the system. The shock wave remained planar inside of the shock tube and lost its planarity upon exiting. The peak overpressure and pressure impulse decayed rapidly upon exit from the shock tube, reducing by 92-95%. The primary flow phenomenon, or the planar shock front, is observed within the shock tube, while two distinct flow phenomena are a result of the shock wave exiting the confines of the shock tube. A vortex ring is formed as the shock wave exited the shock tube into the still, ambient air, which induces a large increase in the total pressure impulse. Additionally, a rarefaction wave was formed following shock front expansion, which traveled upstream into the shock tube, reducing the total and incident pressure impulses for approximately half of the simulated region. OPEN ACCESS Citation: Kahali S, Townsend M, Mendez Nguyen M, Kim J, Alay E, Skotak M, et al. (2020) The evolution of secondary flow phenomena and their effect on primary shock conditions in shock tubes: Experimentation and numerical model. PLoS ONE 15(1): e0227125. https://doi.org/10.