Biomedical subjects

Hironobu Morita

Publications and source records attributed to Hironobu Morita.

At least 19 recordsLinked to original sources

PubMed2026

Selective saccular plasticity under microgravity links peripheral transcriptomic remodeling to postflight vestibular dysfunction.

Long-duration exposure to microgravity disrupts human balance and spatial orientation, yet the molecular mechanisms underlying vestibular adaptation to spaceflight remain poorly understood. Here, we tested the hypothesis that the saccule, the primary gravity-sensing otolith organ, undergoes selective remodeling during spaceflight and contributes to transient postflight postural instability. Using a cross-species approach, we combined transcriptomic analysis of mouse otolith organs with physiological assessments in astronauts. Laser microdissection-based RNA sequencing of mouse otolith sensory epithelia after a 35-d spaceflight revealed pronounced, organ-specific transcriptomic remodeling in the saccule, whereas the utricle remained stable. Principal component and clustering analyses demonstrated that the saccular transcriptome shifted toward an utricle-like profile under microgravity, accompanied by changes in genes related to synaptic and neuronal function. Promoter motif analysis identified NFAT-associated transcriptional networks, suggesting Ca2+-dependent regulation of synaptic plasticity as a potential molecular substrate of gravity-dependent adaptation. In parallel, vestibular testing in astronauts following long-duration missions (157 to 328 d) revealed selective attenuation of saccule-mediated cervical vestibular-evoked myogenic potentials and increased postural sway immediately after return to Earth, while utricle-mediated responses and semicircular canal function were preserved. Both saccular function and postural stability recovered within approximately 10 d. Notably, early postflight postural instability was partially mitigated by noisy galvanic vestibular stimulation, consistent with stochastic resonance-mediated sensory enhancement. Together, these findings identify the saccule as a plastic gravity sensor and establish a mechanistic link between peripheral molecular remodeling and functional balance deficits after spaceflight, providing a framework for developing countermeasures to facilitate vestibular readaptation during human space exploration.

Animals↗

PubMed2006

Long-term hypergravity induces plastic alterations in vestibulo-cardiovascular reflex in conscious rats.

To test the hypothesis that an altered gravitational environment induces plastic changes in the vestibulo-cardiovascular reflex, arterial pressure (AP) and hypothalamic glutamate concentration were examined in 2 groups of conscious rats, i.e., a 3-G group and a 1-G group, in which rats were maintained under a 3-G and 1-G environment for 2 weeks, respectively. The vestibulo-cardiovascular reflex was stimulated by a gravitational change induced by a parabolic flight that consisted of 3 phases: "pull-up", during which the G load gradually increased to 2G; a 20s "push-over" into microgravity; and "pull-out", during which the G load increased to 1.8. In the 1-G group, the AP increased by 11.9+/-1.2 mmHg during the pull-up hypergravity period. The AP response was significantly attenuated in the 3-G group (4.0+/-0.8 mmHg). During the push-over microgravity period, the AP decreased from the peak level in the pull-up period and recovered to the pre-parabolic control level (-1.8+/-2.4 mmHg). In rats of the 3-G group, the AP was not altered by push-over microgravity. These AP responses were associated with a significant increase in the glutamate concentration in the hypothalamus (4.4+/-0.7%). The glutamate response was also significantly attenuated in the 3-G group compared with that in the 1-G group. These results indicate that an altered gravitational environment induces plastic alterations in the vestibulo-cardiovascular reflex.

Animals↗

PubMed2006

Neuromuscular electrical stimulation and an ottoman-type seat effectively improve popliteal venous flow in a sitting position.

The aim of this study was to examine the effects of the sitting posture on the lower limb venous flow and to explore the beneficial effects of neuromuscular electrical stimulation (NMES) and an ottoman-type seat on the venous flow. Healthy adult volunteers without a history of lower limb surgery or thromboembolism were recruited, and the flow velocity, cross-sectional area, and flow volume of the popliteal vein were measured using Doppler ultrasound. A posture change from the prone position to the sitting position on the ottoman-type seat decreased the flow velocity and increased the cross-sectional area of the popliteal vein, and the flow volume was not altered over 120 min. The flow velocity was further decreased, and the cross-sectional area was further increased by subjects sitting on a regular driving seat when compared with the values obtained with an ottoman-type seat. The popliteal flow velocity in the NMES leg was significantly higher than in the non-NMES leg throughout the 120-min testing in the sitting position, but no difference in the cross-sectional area was found between the NMES and the non-NMES legs. Thus lower limb venous stasis elicited by the sitting posture was improved by the ottoman-type seat and NMES.

Adult↗

PubMed2005

Roles of the vestibular system in controlling arterial pressure in conscious rats during a short period of microgravity.

In order to evaluate the roles of the vestibular system in controlling arterial pressure (AP) during exposure to a short period of microgravity (microG), the AP was measured in conscious free-moving rats having intact vestibular systems and those having vestibular lesions (FM-Intact and FM-VL groups, respectively). During free drop-induced microG, the AP increased in the FM-Intact group; it was 38+/-4 mmHg more than the AP observed during 1G. However, the increase in AP was significantly lower in the FM-VL group (20+/-2 mmHg). Further, to examine the sudden effect of a body floating in the midair in response to the AP during exposure to muG a body stabilizer was placed on the back of rats having intact vestibular systems and those having vestibular lesions (STAB-Intact and STAB-VL groups, respectively). The increase in the AP was significantly depressed in the STAB-Intact group; when compared with that in the FM-Intact group, but the increase was still significant (27+/-2 mmHg). On the other hand, the increase in the AP was completely eliminated in the STAB-VL group (7+/-5 mmHg). These results indicate that the AP increases during exposure to muG in conscious rats, and the vestibular system and body stability are significantly involved in this response.

Animals↗

PubMed2005

Effects of high NaCl diet on arterial pressure in Sprague-Dawley rats with hepatic and sinoaortic denervation.

The Na(+) receptor that exists in the hepatoportal region plays an important role in postprandial natriuresis and the regulation of Na(+) balance during NaCl load. Thus it would be considered that a dysfunction of the hepatic Na(+) receptor might result in the elevation of arterial pressure under a condition of high NaCl diet. To elucidate this hypothesis, arterial pressure was continuously measured during three weeks of high NaCl diet (8% NaCl) in four groups of rats: (i) intact rats, (ii) rats with hepatic denervation (HD), (iii) rats with sinoaortic denervation (SAD), and (iv) rats with SAD+HD. During a 1-week normal NaCl diet period, there was no difference in arterial pressure among the four groups. A high NaCl diet had no influence on arterial pressure in intact or HD rats; however, it significantly increased by 11 +/- 3 mmHg in SAD rats. The addition of HD to SAD had no synergistic effect on arterial pressure; i.e., in SAD+HD rats, mean arterial pressure increased by 13 +/- 1 mmHg. In conclusion, sinoaortic baroreceptor, but not hepatic Na(+) receptor, has a significant role in the long-term regulation of arterial pressure on a high NaCl diet.

Animals↗

PubMed2005

Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.

Adaptation, Physiological↗

PubMed2005

Controlling arterial blood pressure using a computer-brain interface.

There has been recent interest in the concept of connecting a computer to the brain to control brain functions. However, there are challenges that must be overcome in developing such a computer-brain interface, including a selection of nucleus that is stimulated, and an implantable electrode and electrical stimulator. Another important issue is the designing of the controller, that is, determining how to encode as an electrical signal the information to be sent to the brain. We have applied system identification theory, a method for evaluating dynamic characteristics of a system, to the arterial blood pressure control system of the brain. Our results show that (1) the stimulation-arterial blood pressure response relationship can be described as a mathematical model, which gives a good prediction of the arterial blood pressure response, facilitating the designing of a computer-brain interface, and (2) the arterial blood pressure can be actually controlled using a computer-brain interface.

Animals↗

PubMed2005

Change in intrathoracic pressure in rats with spontaneous and controlled ventilation during microgravity by parabolic flight.

We previously reported that the intrathoracic pressure (ITP) decreases and the transmural pressure of the aortic wall (TMP) increases during 4.5 s of microgravity (muG) induced by free drop. To examine the ITP response to a longer period of muG in the absence of the respiratory rate (RR) decrease, i.e., bradypnea, which occurs at the onset of muG, we measured the aortic blood pressure at the diaphragma level (AP) and ITP. We then calculated the TMP at the aortic arch level during 20 s of muG induced by parabolic flight in anesthetized rats (n = 7) with either spontaneous ventilation (SPN-V) or controlled ventilation (CONT-V). In the SPN-V group, the bradypnea was observed in all rats after the onset of the muG (RR change -13.9 +/- 2.9/min). The ITP during muG (-9.3 +/- 0.9 mmHg) was significantly lower than that during 1 G (-7.7 +/- 0.9 mmHg), and the TMP was significantly increased during muG (112 +/- 6 mmHg) compared to 1 G (103 +/- 5 mmHg). Similar changes in ITP and TMP were observed in the CONT-V group: During muG and 1G, respectively, the ITP was -8.4 +/- 0.6 mmHg and -5.9 +/- 0.7 mmHg, and the TMP was 112 +/- 6 mmHg and 101 +/- 6 mmHg, whereas no change in RR was observed because of the controlled ventilation. These results show that the ITP decreases and the TMP increases during muG, and they are not affected by a disturbance of respiratory rhythm.

Anesthesia↗

PubMed2004

Vestibulosympathetic reflex mediates the pressor response to hypergravity in conscious rats: contribution of the diencephalon.

To investigate the mechanism of arterial pressure (AP) regulation during hypergravity, the AP response to gravitational force was examined in conscious rats and the AP was found to increase, depending on the degree of gravity load induced by centrifugation. At 20 s after application of 2, 3, or 5 G, the AP increased by 9+/-2, 20+/-3, or 24+/-3 mm Hg, respectively. The AP increase during first 60 s was suppressed by vestibular lesion or pretreatment with hexamethonium, suggesting that the vestibular system and sympathetic nerve system be involved, respectively, in the afferent and efferent pathways. To further examine the central pathway of this response, Fos expression in the brain was examined after exposure to 5 G for 90 min. Intense Fos expression was seen in the medial vestibular nucleus, paraventricular hypothalamic nucleus, autonomic nuclei in the brain stem in intact rats, but not in rats with vestibular lesion. To examine the involvement of the diencephalic nuclei in this pressor response, AP was measured under hypergravity in rats with midcollicular transection. In these rats, the AP change was minimal at 2, 3, and 5 G, indicating that nuclei rostral to the transection level were involved in the pressor response. These results indicate that output from the vestibular system project to the diencephalon, and activation of diencephalic nuclei is indispensable to the pressor response via the sympathetic nerve system.

Analysis of Variance↗

PubMed2004

Sequence of forebrain activation induced by intraventricular injection of hypertonic NaCl detected by Mn2+ contrasted T1-weighted MRI.

In order to define the sequence of forebrain activation involved in osmoregulation, central activation in response to intracerebroventricular injection of NaCl solution (10 microl of 0.15, 0.5, or 1.5 M) was detected using manganese-contrasted magnetic resonance imaging (MRI) in anesthetized rats. Changes in renal sympathetic nerve activity (RNA) were also measured, and the time courses of forebrain activation and RNA changes compared. NaCl injection resulted in rapid activation of the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), and periventricular regions and the lateral hypothalamic area (LHA), then of the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON). The delay in activation in the PVN and SON showed a wide variation from 0 to 5.78 min, and the average delay in the PVN (2.88+/-0.34 min) and SON (2.90+/-0.39 min) was significantly greater than that in the SFO (0.40+/-0.10 min) and OVLT (0.74+/-0.13 min). NaCl (1.5 M) injection elicited a rapid, large increase in RNA, which consisted of two components, an early rapid increase at 99 s after injection (160+/-27%) and a slower increase at 9 min after injection (209+/-34%). These results suggest that the PVN and SON are activated not only by the afferent input from the SFO and OVLT but also by diffusion of the hypertonic stimulus to these regions and probably by their intrinsic osmosensitivity. The PVN might be responsible for the second slower component of the RNA response, but cannot be responsible for the first component.

Animals↗

PubMed2004

Acute hemodynamic responses in the head during microgravity induced by free drop in anesthetized rats.

To examine acute hemodynamic responses to microgravity (microG) in the head, we measured carotid artery pressure (CAP) and jugular vein pressure (JVP) to calculate cephalic perfusion pressure (CPP = CAP - JVP) and recorded images of microvessels in the iris to evaluate capillary blood flow velocity (CBFV) and capillary diameter (CD) in anesthetized rats during 4.5 s of microG induced by free drop. Rats were placed in 30 degrees head-up whole body-tilted (HU, n = 7) or horizontal (flat, n = 6) position. In the flat group, none of the measured variables was significantly affected by microG, whereas in the HU group, CAP, JVP, and CPP increased, respectively, by 23.4 +/- 2.6, 1.3 +/- 0.2, and 22.9 +/- 3.1 mmHg, and CBFV and CD increased, respectively, by 33 +/- 8 and 9 +/- 3%, showing an increase in capillary blood flow. To further examine the mechanisms underlying these CAP and JVP increases, another experiment was performed in which CAP and JVP were measured in anesthetized rats (n = 6) during a postural change from HU to flat. In these animals, the change in JVP was similar to that observed during actual microG, but no change in CAP was seen, indicating that the JVP increase during actual microG is caused by disappearance of the gravitational pressure gradient in the head-to-foot axis, whereas the CAP increase is not. In conclusion, actual microG elicits an increase in CPP due to a greater increase in CAP than JVP, resulting in increased capillary blood flow. Although the increase in JVP is explained by the disappearance of gravitational pressure gradient in the head-to-foot axis as a result of microG, the larger increase in CAP is not.

Anesthesia↗

PubMed2003

Effect of high-NaCl or high-KCl diet on hepatic Na+- and K+-receptor sensitivity and NKCC1 expression in rats.

We previously reported that the bumetanide-sensitive Na(+)-K(+)-2Cl- cotransporter (NKCC1) is involved in the hepatic Na+ and K+ sensor mechanism. In the present study, we examined the effects of a high-NaCl or high-KCl diet on hepatic Na+ and K+ receptor sensitivity and NKCC1 expression in the liver of Sprague-Dawley rats. RT-PCR and Western blots were used to measure NKCC1 mRNA and protein expression, respectively. Infusion of hypertonic NaCl or isotonic KCl + NaCl solutions into the portal vein increased hepatic afferent nerve activity (HANA) in a Na+ or K+ dose-dependent manner. After 4 wk on a high-NaCl or high-KCl diet, HANA responses were attenuated compared with animals fed a normal diet, and NKCC1 expression was reduced. These results show that a high-NaCl or high-KCl diet decreases NKCC1 expression in the liver, and it might cause a reduction in hepatic Na(+)- and K(+)-receptor sensitivity.

Animals↗

PubMed2003

Roles of baroreflex and vestibulosympathetic reflex in controlling arterial blood pressure during gravitational stress in conscious rats.

Gravity acts on the circulatory system to decrease arterial blood pressure (AP) by causing blood redistribution and reduced venous return. To evaluate roles of the baroreflex and vestibulosympathetic reflex (VSR) in maintaining AP during gravitational stress, we measured AP, heart rate (HR), and renal sympathetic nerve activity (RSNA) in four groups of conscious rats, which were either intact or had vestibular lesions (VL), sinoaortic denervation (SAD), or VL plus SAD (VL + SAD). The rats were exposed to 3 G in dorsoventral axis by centrifugation for 3 min. In rats in which neither reflex was functional (VL + SAD group), RSNA did not change, but the AP showed a significant decrease (-8 +/- 1 mmHg vs. baseline). In rats with a functional baroreflex, but no VSR (VL group), the AP did not change and there was a slight increase in RSNA (25 +/- 10% vs. baseline). In rats with a functional VSR, but no baroreflex (SAD group), marked increases in both AP and RSNA were observed (AP 31 +/- 6 mmHg and RSNA 87 +/- 10% vs. baseline), showing that the VSR causes an increase in AP in response to gravitational stress; these marked increases were significantly attenuated by the baroreflex in the intact group (AP 9 +/- 2 mmHg and RSNA 38 +/- 7% vs. baseline). In conclusion, AP is controlled by the combination of the baroreflex and VSR. The VSR elicits a huge pressor response during gravitational stress, preventing hypotension due to blood redistribution. In intact rats, this AP increase is compensated by the baroreflex, resulting in only a slight increase in AP.

Animals↗

PubMed2003

Relationship between transmural pressure and aortic diameter during free drop-induced microgravity in anesthetized rats.

To test the hypothesis that the aortic wall is stretched without increasing aortic pressure (AP) during microgravity (microG), the AP, intrathoracic pressure (ITP), and aortic diameter (AD) were measured in anesthetized Sprague-Dawley rats during 4.5 s of microG produced by freefall. A smooth and immediate reduction in gravity (G) occurred during freefall, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate increase in AD, which was not accompanied by an increase in AP. However, the ITP decreased during microG resulted in an increase in the calculated transmural pressure (TP = AP-ITP) of the aortic wall. A simple linear regression analysis showed that the slopes of the plot of AP vs. AD differed at 1 G and microG, whereas those for the plot of TP vs. AD did not. Thus, the increase in AD during microG was accounted for by the increase in TP. These results suggest that a decrease in ITP, resulting in an increase in TP of the aorta, is a key issue in understanding cardiovascular responses to microG.

Anesthesia↗

PubMed2003

Cerebral circulation during acute microgravity induced by free drop in anesthetized rats.

To evaluate changes in the cerebral circulation during acute microgravity (microG), we measured intracranial pressure (ICP), aortic pressure at the diaphragm level, and cerebral flow velocity (CFV) in anesthetized rats (n = 5) during 4.5 s of microG induced by free drop, then calculated arterial pressure at the eye level (AP(eye)) and cerebral perfusion pressure (CPP = AP(eye)-ICP), and estimated CPP-CFV relationship. The rats were placed in the flat and the 30 degrees head-up positions. In the head-up position, ICP, AP(eye), and CPP were significantly increased by 2.2 +/- 0.4, 12.3 +/- 2.0, and 10.1 +/- 1.7 mmHg respectively during microG, whereas the CFV did not change significantly. In the flat position, none of these variables were significantly affected by microG. The slope of the CPP-CFV relationship was decreased only in the head-up position, suggesting that the cerebrovascular resistance was increased by microG. These findings indicate that the change in gravitational (hydrostatic) pressure is a key factor in understanding the changes in cerebral circulation during acute microG.

Animals↗

PubMed2003

R-R interval variability with lower body positive pressure assessed by wavelet packet transform.

Lower body positive pressure (LBPP) is used for simulation of microgravity due to central fluid shift. In the present study, we evaluate R-R interval variability, which is sometimes considered as an index of human cardiovascular autonomic nerve status. 10 healthy male subjects were set in a chamber with standing position. Chamber pressure was raised 10 mmHg each for every 3 minutes, up to +40 mmHg. Wavelet packet transform (WPT) followed by Hilbert transform was employed to analyze time-dependent changes in low frequency component (LF) and high frequency component (HF) of R-R interval variability. Calf circumference lowered according to chamber pressure. ABP was maintained throughout measurements. R-R interval was significantly higher at +30 and +40 mmHg compared to that of control. Standing LBPP causes higher HF and lower L/H probably due to central fluid shift, and WPT followed by Hilbert transform shows time-dependent changes in R-R interval variability.

Atmosphere Exposure Chambers↗

PubMed2003

Cerebral hemodynamics during microgravity.

As one of the causes of the space adaptation syndrome, an increased intracranial pressure due to the cephalad fluid shift is suggested. In the present study, we measured intracranial pressure (ICP), aortic pressure and cerebral flow velocity (CFV) in anesthetized rats (n=5) during 4.5 sec of microgravity induced by free drop. The rats were set at horizontal prone (Flat) and 30-degree head-up whole body tilting (HU) positions to examine the effect of gravitational pressure gradient. Then, arterial pressure at the eye level (APeye), cerebral perfusion pressure (CPP; CPP=APeye-ICP), and CPP-CFV relationship was calculated. In HU position, ICP, APeye, and CPP increased by 2.2 +/- 0.4, 12.3 +/- 2.0, and 10.1 +/- 1.7 mmHg respectively. However, CFV did not change significantly. In Flat position, none of these variables did not change significantly. In HU position the slope of CPP-CFV relationship decreased, suggesting the increased cerebral flow resistance. However, it did not change in Flat position. These results can be understood by the disappearance of gravitational pressure gradient by microgravity and the cerebral autoregulation.

Animals↗

PubMed2003

Skin blood flow with elastic compressive extravehicular activity space suit.

During extravehicular activity (EVA), current space suits are pressurized with 100% oxygen at approximately 222 mmHg. A tight elastic garment, or mechanical counter pressure (MCP) suit that generates pressure by compression, may have several advantages over current space suit technology. In this study, we investigated local microcirculatory effects produced with negative ambient pressure with an MCP sleeve. The MCP glove and sleeve generated pressures similar to the current space suit. MCP remained constant during negative pressure due to unchanged elasticity of the material. Decreased skin capillary blood flow and temperature during MCP compression was counteracted by greater negative pressure or a smaller pressure differential.

Adult↗