Steady-state cerebral blood flow and dynamic cerebral autoregulation during neck flexion and extension in seated healthy young adults.

Neck flexion and extension show differences in various physiological factors, such as sympathetic nerve activity and intracranial pressure (ICP). We hypothesized that differences would exist in steady-state cerebral blood flow and dynamic cerebral autoregulation between neck flexion and extension in seated, healthy young adults. Fifteen healthy adults were studied in the sitting position. Data were collected during neck flexion and extension in random order for 6 min each on the same day. Arterial pressure at the heart level was measured using a cuff sphygmomanometer. Mean arterial pressure at the middle cerebral artery (MCA) level (MAPMCA ) was calculated by subtracting the hydrostatic pressure difference between heart and MCA levels from mean arterial pressure at the heart level. Non-invasive cerebral perfusion pressure (nCPP) was estimated as the MAPMCA minus the non-invasive ICP as determined from transcranial Doppler ultrasonography. Waveforms of arterial pressure in the finger and blood velocity in the MCA (MCAv) were obtained. Dynamic cerebral autoregulation was evaluated by transfer function analysis between these waveforms. The results showed that nCPP was significantly higher during neck flexion than during neck extension (p = 0.004). However, no significant differences were observed in mean MCAv (p = 0.752). Likewise, no significant differences were observed in any of the three indices of dynamic cerebral autoregulation in any frequency range. Although non-invasively estimated cerebral perfusion pressure was significantly higher during neck flexion than during neck extension, no differences in steady-state cerebral blood flow or dynamic cerebral autoregulation were evident between neck flexion and extension in seated healthy adults.

Alteration in facial skin blood flow during acute exposure to -10 and -30° head-down tilt in young human volunteers.

NEW FINDINGS: What is the central question of this study? Facial skin blood flow (SBF) might increase during head-down tilt (HDT). However, the effect of HDT on facial SBF remains controversial. In addition, the changes in facial SBF in the cheek (cheek SBF) during a steeper angle of HDT (>-12° HDT) have not been investigated. What is the main finding and its importance? This study showed that cheek SBF decreased during -30° HDT, alongside increased vascular resistance. Furthermore, vascular impedance was suggested to be elevated, accompanied by an increased hydrostatic pressure gradient caused by HDT. Constriction of the facial skin vascular bed and congestion of venous return owing to the steep angle of HDT can decrease facial SBF. ABSTRACT: Head-down tilt (HDT) has been used to simulate microgravity in ground-based studies and clinical procedures including the Trendelenburg position or in certain surgical operations. Facial skin blood flow (SBF) might be altered by HDT, but the effect of a steeper angle of HDT (>-12° HDT) on facial SBF remains unclear. We examined alterations in facial SBF in the cheek (cheek SBF) using two different angles (-10 and -30°) of HDT and lying horizontal (0°) in a supine position for 10 min, to test the hypothesis that cheek SBF would increase with a steeper angle of HDT. Cheek SBF was measured continuously by laser Doppler flowmetry. Cheek skin vascular resistance and the pulsatility index of cheek SBF were calculated to assess the circulatory effects on the facial skin vascular bed in the cheek. Cheek SBF decreased significantly during -30° HDT. In addition, the resistance in cheek SBF increased significantly during -30° HDT. The pulsatility index of cheek SBF increased during both -10 and -30° HDT. Contrary to our hypothesis, cheek SBF decreased during -30° HDT along with increased skin vascular resistance. Vascular impedance, estimated by the pulsatility index in the cheek SBF, was elevated during both -10 and -30° HDT, and elevated vascular impedance would be related to increased hydrostatic pressure induced by HDT. Skin vascular constriction and venous return congestion would be induced by -30° HDT, leading to deceased cheek SBF. The present study suggested that facial SBF in the cheek decreased during acute exposure to a steep angle of HDT (∼-30° HDT).

Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

Effects of -10° and -30° head-down tilt on cerebral blood velocity, dynamic cerebral autoregulation, and noninvasively estimated intracranial pressure.

Steady-state cerebral blood flow (CBF) and dynamic cerebral autoregulation are reportedly maintained during -10° head-down tilt (HDT) despite slight increases in intracranial pressure (ICP). However, the higher ICP during -30° HDT may alter steady-state CBF and dynamic cerebral autoregulation. The present study hypothesized that steady-state CBF and dynamic cerebral autoregulation would be altered by higher ICP during -30° HDT than during 0° and -10° HDT. Seventeen healthy participants were positioned horizontal (0°) and in -10° HDT and -30° HDT for 10 min in random order on separate days. The arterial blood pressure waveform was obtained using a finger blood pressure device and the cerebral blood velocity waveform in the middle cerebral artery was obtained using transcranial Doppler sonography (TCD) for the last 6 min in each position. ICP was estimated using noninvasive ICP (nICP) based on TCD. Dynamic cerebral autoregulation was evaluated by spectral and transfer function analysis. Although nICP was significantly higher during -30° HDT (12.4 mmHg) than during -10° HDT (8.9 mmHg), no significant differences in steady-state mean cerebral blood velocity or transfer function gain in any frequency ranges were seen among all angles of HDT. Counter to our hypothesis, the present results suggest that steady-state CBF and dynamic cerebral autoregulation may be preserved during short-term -30° HDT despite the higher ICP compared with that during -10° HDT.NEW & NOTEWORTHY This appears to be the first study to evaluate steady-state cerebral blood flow (CBF), dynamic cerebral autoregulation, and intracranial pressure (ICP) during -30° head-down tilt (HDT) compared with those during -10° HDT using noninvasive measurements. The results suggest that steady-state CBF and dynamic cerebral autoregulation are preserved despite the higher ICP during short-term -30° HDT compared with -10° HDT.

Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity.

KEY POINTS: During long-duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension. In the present study, intracranial pressure was estimated non-invasively (nICP) using a model-based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long-duration spaceflights. Our results show that group-averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long-duration spaceflight rarely increased postflight intracranial pressure. The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post-flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes. Cerebral blood velocity increased independently of nICP and spaceflight-associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long-duration spaceflight. ABSTRACT: Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non-invasively before and after spaceflight to test whether ICP would increase after long-duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4-12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non-invasive ICP (nICP) was computed using a validated model-based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = -0.589, regression coefficient = -4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long-duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long-duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.

Changes in cerebral oxygen saturation and cerebral blood flow velocity under mild +Gz hypergravity.

We previously reported that cerebral blood flow (CBF) was reduced by even mild +Gz hypergravity. Regional cerebral oxygen saturation as measured by near-infrared spectroscopy (C-rSO2) has been widely used to detect cerebral ischemia in clinical practice. For example, decreases in C-rSO2 reflect reduced CBF or arterial oxygen saturation. Thus it was hypothesized that C-rSO2 would decrease in association with reduced CBF during mild hypergravity. To test this hypothesis, we measured CBF velocity by transcranial Doppler ultrasonography and C-rSO2 during mild +Gz hypergravity while participants were in a sitting position. Among 17 male participants, 15 completed 21 min of exposure to +1.5 Gz generated by short-arm centrifuge. C-rSO2 and mean CBF velocity in the middle cerebral artery (MCBFVMCA) during centrifugation were averaged every 5 min and compared with pre-hypergravity (+1.0 Gz). C-rSO2 did not change significantly throughout centrifugation, although MCBFVMCA gradually decreased from the beginning (-1.2% at 0-5 min), and significantly decreased at 5-10 min (-4.8%), 10-15 min (-6.7%), and 15-20 min (-7.4%). Contrary to our hypothesis, decreases in C-rSO2 were not detected, despite reductions in CBF velocity during hypergravity. Since some assumptions, such as unaltered arteriovenous volume ratio, hemoglobin concentration, extracranial blood flow, and brain activity, need to be satisfied to monitor cerebral ischemia by C-rSO2, the present results suggest that these necessary assumptions for near-infrared spectroscopy are not always applicable, and that cerebral oxygenation may not precisely reflect decreases in CBF under mild +Gz hypergravity. NEW & NOTEWORTHY To our knowledge, this is the first study to evaluate simultaneously cerebral oxygenation monitored by near-infrared spectroscopy and cerebral blood flow (CBF) monitored by transcranial Doppler under +1.5 Gz hypergravity. Contrary to our hypothesis, there was no significant correlation between CBF velocity and regional cerebral oxygen saturation (C-rSO2). However, an incomplete case nearly involving syncope suggests the possibility that C-rSO2 can detect a remarkable decrease in CBF with development of presyncope during +Gz hypergravity.

Dynamic cerebral autoregulation after confinement in an isolated environment for 14 days.

BACKGROUND: To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation. METHODS: We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity. RESULTS: Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement. CONCLUSION: The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation. TRIAL REGISTRATION: UMIN000020703 , Registered 2016/01/22.

Time-Dependent Changes in Cerebral Blood Flow and Arterial Pressure During Mild +Gz Hypergravity.

BACKGROUND: Artificial hypergravity has been proposed to prevent or treat various forms of physiological deconditioning experienced during spaceflight. We have previously reported that cerebral blood flow decreased at 15-21 min of +1.5-Gz centrifugation without decreases in arterial pressure at heart level. We reanalyzed our previous data to clarify time-dependent changes in cerebral blood flow and arterial pressure during mild +Gz hypergravity. METHOD: We reanalyzed data for 0-20 min during +1.5-Gz centrifugation on 13 male subjects for whom physiological data were steadily recorded. Mean cerebral blood flow velocity in the middle cerebral artery (MCBFVMCA), mean arterial pressure at heart level (MAPheart), and middle cerebral artery level (MAPMCA) during centrifugation were averaged every 5 min and compared with prehypergravity data (+1.0 Gz, 5 min). RESULTS: MAPheart did not change significantly, but MAPMCA decreased significantly throughout centrifugation compared to prehypergravity data (-16.7% to -24.7%). MCBFVMCA tended to be decreased at 0-5 min of +1.5-Gz centrifugation (-3.3%), but this was not statistically significant. MCBFVMCA was significantly decreased at 5-10 min (-5.5%). MCBFVMCA at 10-15 min and 15-20 min were also significantly decreased to almost the same level (-6.9% and -6.8%, respectively). DISCUSSION: No significant change in MAPheart was detected, whereas MAPMCA decreased significantly from the beginning of +1.5-Gz centrifugation. On the other hand, MCBFVMCA gradually decreased and became roughly flat in the latter half of 20-min centrifugation. Understanding the different time-dependent changes in cerebral blood flow and arterial pressure under mild +Gz hypergravity might be important for implementation of centrifuging as a countermeasure for spaceflight-induced deconditioning.Konishi T, Kurazumi T, Kato T, Takko C, Ogawa Y, Iwasaki K. Time-dependent changes in cerebral blood flow and arterial pressure during mild +Gz hypergravity. Aerosp Med Hum Perform. 2018; 89(9):787-791.

Effects of enriched environment on hippocampal neuronal cell death and neurogenesis in rat global ischemia.

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.