Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise

Dry immersion (DI) is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt). Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement.Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies

Dry immersion as a model of deafferentation: A neurophysiology study using somatosensory evoked potentials.

INTRODUCTION:Dry immersion is a ground-based experiment simulating the effects of weightlessness, and it is a model of acute symmetrical bilateral deafferentation. This exploratory study aimed to investigate the effects of three days of dry immersion (DI) on sensory thresholds and the functioning of lemniscal pathways, assessed by somatosensory evoked potentials (SEPs). METHODS:Twelve healthy male volunteers (32+/-4.8 years) participated in the study. Sensory thresholds and SEPs of the tibial nerve of both limbs were recorded before (D-1) and on the third day of dry immersion (D3). RESULTS:Sensory thresholds significantly decreased on D3 (-20.75 +/-21.7%; z = -2.54; p = 0.0109 on the right side and -22.18+/-17.28%; z = -3.059; p = 0.002 on the left side). The amplitude of P40 responses did not differ between D-1 and D3. Latencies of all central responses until P30 were shortened on D3 (N21 right:-0.57+/-0.31; z = -3.06; p = 0.002; N21 left -0.83+/-0.53; z = -2.94; p = 0.003; P30 right: -1.26+/-1.42; z = -3.059; p = 0.002; P30 left: -1.11+/-1.55; z = -2.27; p = 0.02). CONCLUSION:Three days of dry immersion can induce hyperexcitability of lemniscal pathways. SIGNIFICANCE:This may be explained by a change in the expression of membrane channels and/or medullar plasticity and/or hypersensitization of peripheral sensory receptors induced by this acute deafferentation. Additional studies are needed to further elucidate the mechanisms

Brain Activity during Mental Imagery of Gait Versus Gait-Like Plantar Stimulation: A Novel Combined Functional MRI Paradigm to Better Understand Cerebral Gait Control

International audienceHuman locomotion is a complex sensorimotor behavior whose central control remains difficult to explore using neuroimaging method due to technical constraints, notably the impossibility to walk with a scanner on the head and/or to walk for real inside current scanners. The aim of this functional Magnetic Resonance Imaging (fMRI) study was to analyze interactions between two paradigms to investigate the brain gait control network: (1) mental imagery of gait, and (2) passive mechanical stimulation of the plantar surface of the foot with the Korvit boots. The Korvit stimulator was used through two different modes, namely an organized ("gait like") sequence and a destructured (chaotic) pattern. Eighteen right-handed young healthy volunteers were recruited (mean age, 27 ± 4.7 years). Mental imagery activated a broad neuronal network including the supplementary motor area-proper (SMA-proper), pre-SMA, the dorsal premotor cortex, ventrolateral prefrontal cortex, anterior insula, and precuneus/superior parietal areas. The mechanical plantar stimulation activated the primary sensorimotor cortex and secondary somatosensory cortex bilaterally. The paradigms generated statistically common areas of activity, notably bilateral SMA-proper and right pre-SMA, highlighting the potential key role of SMA in gait control. There was no difference between the organized and chaotic Korvit sequences, highlighting the difficulty of developing a walking-specific plantar stimulation paradigm. In conclusion, this combined-fMRI paradigm combining mental imagery and gait-like plantar stimulation provides complementary information regarding gait-related brain activity and appears useful for the assessment of high-level gait control

Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines

<div><p>Background</p><p>Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones.</p><p>Methods</p><p>Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI_24h, DI_48H and DI_72h), then after recovery (R_+3h and R_+24h). Markers of bone turnover, phosphocalcic metabolism, adipokines and associated factors were measured.</p><p>Results</p><p>Bone resorption as assessed by tartrate-resistant acid phosphatase isoform 5b and N-terminal crosslinked telopeptide of type I collagen levels increased as early as DI_24h. At the same time, total procollagen type I N- and C-terminal propeptides and osteoprotegerin, representing bone formation markers, decreased. Total osteocalcin [OC] was unaffected, but its undercarboxylated form [Glu-OC] increased from DI_24h to R_+3h. The early and progressive increase in bone alkaline phosphatase activities suggested an increased mineralization. Dickkopf-1 and sclerostin, as negative regulators of the Wnt-β catenin pathway, were unaltered. No change was observed either in phosphocalcic homeostasis (calcium and phosphate serum levels, 25-hydroxyvitamin D, fibroblast growth factor 23 [FGF23]) or in inflammatory response. Adiponectemia was unchanged, whereas circulating leptin concentrations increased. Neutrophil gelatinase-associated lipocalin [lipocalin-2], a potential regulator of bone homeostasis, was found elevated by 16% at R_+3h compared to DI_24h. The secretory form of nicotinamide phosphoribosyl-transferase [visfatin] concentrations almost doubled after one day of DI and remained elevated. Serum insulin-like growth factor 1 levels progressively increased. Fasting insulin concentrations increased during the entire DI, whereas fasting glucose levels tended to be higher only at DI_24h and then returned to BDC values. Changes in bone resorption parameters negatively correlated with changes in bone formation parameters. Percent changes of ultra-sensitive C-reactive protein positively correlated with changes in osteopontin, lipocalin-2 and fasting glucose. Furthermore, a positive correlation was found between changes in FGF23 and Glu-OC, the two main osteoblast-/osteocyte-derived hormones.</p><p>Conclusion</p><p>Our results demonstrated that DI induced an unbalanced remodeling activity and the onset of insulin resistance. This metabolic adaptation was concomitant with higher levels of Glu-OC. This finding confirms the role of bone as an endocrine organ in humans. Furthermore, visfatin for which a great responsiveness was observed could represent an early and sensitive marker of unloading in humans.</p></div

Association between biochemical blood markers.

<p>Spearman correlations between percent changes at DI_48h in bone and energy metabolism parameters for n = 12 except for NTx* which was made for n = 6 only. Changes are expressed in percent from BDC. OPN: osteopontin; usCRP: ultrasensitive C-reactive protein; P1CP: procollagen type I C-terminal propeptide; CTx: C-terminal crosslinked telopeptide of type I collagen; OC: osteocalcin; Gal-OC and Glu-OC: carboxylated and uncarboxlalted forms of OC, respectively; NTx: N-terminal crosslinked telopeptide of type I collagen; usCRP: ultrasensitive C-reactive protein; FGF23: fibroblast growth factor 23.</p

Serum markers for different metabolic pathways during the 3-day dry immersion and/or after 24 h- recovery.

<p>Serum markers for different metabolic pathways during the 3-day dry immersion and/or after 24 h- recovery.</p

Effect of dry immersion on bone metabolism.

<p>Changes in bone resorption (at left) and formation or mineralization (at right) markers during dry immersion. Values are expressed as medians ± interquartile range for n = 12 except for NTx* which was made for n = 6 only. <b>a,b,c</b> indicate significant differences vs. BDC, DI_24h and DI_48h, respectively. CTx: C-terminal crosslinked telopeptide of type I collagen; NTx: N-terminal crosslinked telopeptide of type I collagen; TRAP5b: tartrate-resistant acid phosphatase isoform 5b; P1CP: procollagen type I C-terminal propeptide; P1NP: procollagen type I N-terminal propeptide; bAP: bone alkaline phosphatase.</p

Serum markers for bone turnover and bone metabolism regulators during the 3-day dry immersion and after 3 h- recovery.

<p>Serum markers for bone turnover and bone metabolism regulators during the 3-day dry immersion and after 3 h- recovery.</p

Description of the study.

<p><b>A</b> Time line of the experiment with the timing of different blood samples. Blue area corresponds to the DI phase. BDC: baseline data collection; DI: dry immersion; R: recovery. <b>B</b> A volunteer in the DI bath.</p

Effect of dry immersion on the different forms of osteocalcin and on the insulinic response.

<p><i>At Top</i>, changes in carboxylated (Gla-OC) and decarboxylated (Glu-OC) forms of osteocalcin during dry immersion. <i>At middle</i>, changes in values of glucose and insulin during dry immersion. <i>At bottom</i>, changes in values of IGF1 and visfatin during dry immersion. Values are medians ± interquartile range for n = 12. <b>a,b,c</b> indicate significant differences vs. BDC, DI_24h and DI_48h, respectively; <b>a’</b> different vs. BDC p<0.10.</p