At-Home "Tips" for Headache Management: The Use of Self-Trendelenburg to Help Determine the Cause of Worsening Headaches - A Case Series.

Introduction: In-office use of the Trendelenburg position has been shown to be a beneficial clinical tool to help decipher if a CSF pressure/volume component is part of the underlying etiologic process for a patient's persistent headache. Utilizing the Trendelenburg position at home could potentially be an additional diagnostic tool for the treating headache physician. Case Series: Our headache practice has been using at-home self-Trendelenburg for the past 2 years and will present the clinical scenarios in which it seems to be the most helpful utilizing a case series of patients. These include (1) in those who just had a lumbar puncture and call for worsening headaches and do not have an obvious orthostatic component; (2) in those who had a spinal epidural blood patch for a presumed CSF leak and state there was no improvement; (3) in those who are on daily preventive CSF volume-lowering medications and call in with worsening headaches; (4) in those with known CSF pressure-dependent headaches high or low but who are not on daily preventive CSF volume modulatory medications; (5) in those with a history of migraine or other primary headache disorder to see if a new type of headache is possibly from a CSF leak or an abnormal reset of CSF pressure to an elevated state; (6) in those with triggered only headaches like cough or exertional headache. Conclusion: Utilizing at-home self-Trendelenburg can provide valuable information for the treating headache physician on possible underlying headache etiology and can guide specific treatment strategies. Its simplicity and quick declaration of results are very patient pleasing.

The reverse Trendelenburg position in proximal ureteral stone management: A systematic review and meta-analysis.

INTRODUCTION: Ureteroscopy lithotripsy (URSL) presents a therapeutic option for patients with proximal ureteral calculi warranting active removal. This systematic review and meta-analysis aimed to assess the efficacy of the reverse Trendelenburg (RT) position during this procedure. MATERIALS: A comprehensive literature search was conducted across PubMed, Embase, and Cochrane databases to identify randomized controlled trials and observational studies comparing RT versus standard positioning (STD) in patients undergoing URSL for proximal ureteral stones. Heterogeneity was measured with the Cochran's Q test, I2 statistics, and prediction intervals (PI). A DerSimonian and Laird random-effects model was utilized for all outcomes. RESULTS: Four studies encompassing 505 patients undergoing URSL were analyzed. Among the studied participants, 293 (58%) underwent RT positioning. Overall, RT was associated with a lower average incidence of stone retropulsion (RR 0.42; 95% CI 0.27-0.65; I2=48%; PI 0.08-2.10) and a higher mean stone-free rate (RR 1.33; 95% CI 1.18-1.49; I2=0%). However, no significant difference between groups was found in the mean rate of overall complications (RR 0.76; 95% CI 0.40-1.43; I2=51%; PI 0.00-520.22) and operative time (MD -0.65; 95% CI -9.58-8.27; I2=94%; PI -111.95-110.65). In those with proximal ureteral stones undergoing RT positioning at only the 20° angle, there was a reduction in stone retropulsion without any measured heterogeneity (RR 0.35; 95% CI 0.23-0.52; I2=0%). CONCLUSION: These findings suggest that RT positioning is effective in improving outcomes for patients with proximal ureteral stones undergoing URSL, and its use should be considered during the procedure.

Characterization of internal jugular vein region-specific distension and flow patterns during progressive volume shifting.

Blood volume shifts during postural adjustment lead to irregular distension of the internal jugular vein (IJV). In microgravity, distension may contribute to flow stasis and thromboembolism, though the regional implications and associated risk remain unexplored. We characterized regional differences in IJV volume distension and flow complexity during progressive head-down tilt (HDT) (0°, -6°, -15°, -30°) using conventional ultrasound and vector flow imaging. We also evaluated low-pressure thigh cuffs (40 mmHg) as a fluid shifting countermeasure during -6° HDT. Total IJV volume expanded 139 ± 95% from supine position (4.6 ± 2.7 mL) to -30° HDT (10.3 ± 5.0 mL). Blood flow profiles had greater vector uniformity at the cranial IJV region (P < 0.01) and became more dispersed with increasing tilt (P < 0.01). Qualitatively, flow was more uniform throughout the IJV during its early flow cycle phase and more disorganized during late flow phase. This disorganized flow was accentuated closer to the vessel wall, near the caudal region, and during greater HDT. Low-pressure thigh cuffs during -6° HDT decreased IJV volume at the cranial region (-12 ± 15%; P < 0.01) but not the caudal region (P = 0.20), although flow uniformity was unchanged (both regions, P > 0.25). We describe a distensible IJV accommodating large volume shifts along its length. Prominent flow dispersion was primarily found at the caudal region, suggesting multidirectional blood flow. Thigh cuffs appear effective for decreasing IJV volume but effects on flow complexity are minor. Flow complexity along the vessel length is likely related to IJV distension during chronic volume shifting and may be a precipitating factor for flow stasis and future thromboembolism risk.NEW & NOTEWORTHY The internal jugular vein (IJV) facilitates cerebral outflow and is sensitive to volume shifts. Concerns about IJV expansion and fluid flow behavior in astronauts have surfaced following thromboembolism reports. Our study explored regional volume distension and blood flow complexity in the IJV during progressive volume shifting. We observed stepwise volume distension and increasing flow dispersion with head-down tilting across all regions. Flow dispersion may pose a risk of future thromboembolism during prolonged volume shifts.

Rheoencephalography: A non-invasive method for neuromonitoring.

In neurocritical care, the gold standard method is intracranial pressure (ICP) monitoring for the patient's lifesaving. Since it is an invasive method, it is desirable to use an alternative, noninvasive technique. The computerized real-time invasive cerebral blood flow (CBF) autoregulation (AR) monitoring calculates the status of CBF AR, called the pressure reactivity index (PRx). Studies documented that the electrical impedance of the head (Rheoencephalography - REG) can detect the status of CBF AR (REGx) and ICP noninvasively. We aimed to test REG to reflect ICP and CBF AR. For nineteen healthy subjects we recorded bipolar bifrontal and bitemporal REG derivations and arm bioimpedance pulses with a 200 Hz sampling rate. The challenges were a 30-second breath-holding and head-down-tilt (HDT - Trendelenburg) position. Data were stored and processed offline. REG pulse wave morphology and REGx were calculated. The most relevant finding was the significant morphological change of the REG pulse waveform (2nd peak increase) during the HDT position. Breath-holding caused REG amplitude increase, but it was not significant. REGx in male and female group averages have similar trends during HDT by indicating the active status of CBF AR. The morphological change of REG pulse wave during HDT position was identical to ICP waveform change during increased ICP, reflecting decreased intracranial compliance. A correlation study between ICP and REG was initiated in neurocritical care patients. The noninvasive REG monitoring would also be useful in space research as well as in military medicine during the transport of wounded service members as well as for fighter pilots to indicate the loss of CBF and consciousness.

Effects of 30 days bed rest and exercise countermeasures on PBMC bioenergetics.

AIM: Altered mitochondrial function across various tissues is a key determinant of spaceflight-induced physical deconditioning. In comparison to tissue biopsies, blood cell bioenergetics holds promise as a systemic and more readily accessible biomarker, which was evaluated during head-down tilt bed rest (HDTBR), an established ground-based analog for spaceflight-induced physiological changes in humans. More specifically, this study explored the effects of HDTBR and an exercise countermeasure on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). METHODS: We subjected 24 healthy participants to a strict 30-day HDTBR protocol. The control group (n = 12) underwent HDTBR only, while the countermeasure group (n = 12) engaged in regular supine cycling exercise followed by veno-occlusive thigh cuffs post-exercise for 6 h. We assessed routine blood parameters 14 days before bed rest, the respiratory capacity of PBMCs via high-resolution respirometry, and citrate synthase activity 2 days before and at day 30 of bed rest. We confirmed PBMC composition by flow cytometry. RESULTS: The change of the PBMC maximal oxidative phosphorylation capacity (OXPHOS) amounted to an 11% increase in the countermeasure group, while it decreased by 10% in the control group (p = 0.04). The limitation of OXPHOS increased in control only while other respiratory states were not affected by either intervention. Correlation analysis revealed positive associations between white blood cells, lymphocytes, and basophils with PBMC bioenergetics in both groups. CONCLUSION: This study reveals that a regular exercise countermeasure has a positive impact on PBMC mitochondrial function, confirming the potential application of blood cell bioenergetics for human spaceflight.

Mesial temporal atrophy in preoperative MRI rather than steep Trendelenburg position is associated with postoperative delirium in patients undergoing a major urologic surgery.

PURPOSE: To investigate whether steep Trendelenburg in a major urologic surgery is associated with postoperative delirium, and to examine other potential clinical and radiologic factors predictive of postoperative delirium. METHODS: 182 patients who received a major urologic surgery and underwent a 3.0-T brain MRI scan within 1 year prior to the date of surgery were retrospectively enrolled. Preoperative brain MRIs were used to analyze features related to small vessel disease burden and mesial temporal atrophy. Presence of a significant mesial temporal atrophy was defined as Scheltens' scale ≥ 2. Patients' clinico-demographic data and MRI features were used to identify significant predictors of postoperative delirium using the logistic regression analysis. Independent predictors found significant in the univariate analysis were further evaluated in the multivariate analysis. RESULTS: Incidence of postoperative delirium was 6.0%. Patients with postoperative delirium had lower body mass index (21.3 vs. 25.0 kg/m2, P = 0.003), prolonged duration of anesthesia (362.7 vs. 224.7 min, P < 0.001) and surgery (302.2 vs. 174.5 min, P < 0.001), and had more significant mesial temporal atrophy (64% vs. 30%, P = 0.046). In the univariate analysis, female sex, type of surgery (radical prostatectomy over cystectomy), prolonged duration of anesthesia (≥ 6 h), and presence of a significant mesial temporal atrophy were significant predictors (all P-values < 0.050), but only the presence of significant mesial temporal atrophy was significant in the multivariate analysis [odds ratio (OR), 3.69; 95% CI 0.99-13.75; P = 0.046]. CONCLUSION: Steep Trendelenburg was not associated with postoperative delirium. Significant mesial temporal atrophy (Scheltens' scale ≥ 2) in preoperative brain MRI was predictive of postoperative delirium. TRIAL REGISTRATION: Not applicable.

Head-down tilt reduces the heart rate in postural tachycardia syndrome in acute setting: a pilot study.

BACKGROUND: Reduced preload and thoracic blood volume accompany postural tachycardia syndrome (POTS). Head-down tilt (HDT) increases both preload and intrathoracic blood volume. The objective of this study was to assess the safety and efficacy of HDT in POTS in acute settings. METHODS: This retrospective study evaluated POTS patients. Analyzed data included heart rate, blood pressure, cerebral blood flow velocity (CBFv) in the middle cerebral artery, and capnography. The baseline supine hemodynamic data were compared with the data obtained at the second minute of the -10° HDT. A linear mixed-effects model was used to assess the effect of HDT on hemodynamic variables. RESULTS: The HDT was explored in seven POTS patients and an additional seven POTS patients without HDT served as controls. In the HDT arm, four POTS patients had overlapping diagnoses of myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) and one patient had comorbidity of post-acute sequelae of SARS-CoV-2 infection (PASC). HDT lowered heart rate by 10% and increased end-tidal CO2 by 8%. There was no change in other cardiovascular variables. CONCLUSIONS: In the acute setting, HDT is safe. HDT reduces the heart rate presumably by modulating baroreflex by enhancing preload and stroke volume, which in turn increases thoracic blood volume with a net effect of parasympathetic cardiovagal activation and/or sympathetic withdrawal. This pilot study provides a foundation to proceed with longitudinal studies exploring the long-term effect of repetitive HDT in conditions associated with preload failure such as POTS, ME/CSF, and PASC.

Effects of head-down tilt on optic nerve sheath diameter in healthy subjects.

PURPOSE: Intracranial pressure increases in head-down tilt (HDT) body posture. This study evaluated the effect of HDT on the optic nerve sheath diameter (ONSD) in normal subjects. METHODS: Twenty six healthy adults (age 28 [4.7] years) participated in seated and 6° HDT visits. For each visit, subjects presented at 11:00 h for baseline seated scans and then maintained a seated or 6° HDT posture from 12:00 to 15:00 h. Three horizontal axial and three vertical axial scans were obtained at 11:00, 12:00 and 15:00 h with a 10 MHz ultrasonography probe on the same eye, randomly chosen per subject. At each time point, horizontal and vertical ONSD (mm) were quantified by averaging three measures taken 3 mm behind the globe. RESULTS: In the seated visit, ONSDs were similar across time (p > 0.05), with an overall mean (standard deviation) of 4.71 (0.48) horizontally and 5.08 (0.44) vertically. ONSD was larger vertically than horizontally at each time point (p < 0.001). In the HDT visit, ONSD was significantly enlarged from baseline at 12:00 and 15:00 h (p < 0.001 horizontal and p < 0.05 vertical). Mean (standard error) horizontal ONSD change from baseline was 0.37 (0.07) HDT versus 0.10 (0.05) seated at 12:00 h (p = 0.002) and 0.41 (0.09) HDT versus 0.12 (0.06) seated at 15:00 h (p = 0.002); mean vertical ONSD change was 0.14 (0.07) HDT versus -0.07 (0.04) seated at 12:00 h (p = 0.02) and 0.19 (0.06) HDT versus -0.03 (0.04) seated at 15:00 h (p = 0.01). ONSD change in HDT was similar between 12:00 and 15:00 h (p ≥ 0.30). Changes at 12:00 h correlated with those at 15:00 h for horizontal (r = 0.78, p < 0.001) and vertical ONSD (r = 0.73, p < 0.001). CONCLUSION: The ONSD increased when body posture transitioned from seated to HDT position without any further change at the end of the 3 h in HDT.

Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial.

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; - 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Effects of short-term -30° HDT on contrast sensitivity.

Potential cognitive and physiological alterations due to space environments have been investigated in long-term space flight and various microgravity-like conditions, for example, head-down tilt (HDT), confinement, isolation, and immobilization. However, little is known about the influence of simulated microgravity environments on visual function. Contrast sensitivity (CS), which indicates how much contrast a person requires to see a target, is a fundamental feature of human vision. Here, we investigated how the CS changed by 1-h -30° HDT and determined the corresponding mechanisms with a perceptual template model. A quick contrast sensitivity function procedure was used to assess the CS at ten spatial frequencies and three external noise levels. We found that (1) relative to the + 30° head-up tilt (HUT) position, 1-h -30° HDT significantly deteriorated the CS at intermediate frequencies when external noise was present; (2) CS loss was not detected in zero- or high-noise conditions; (3) HDT-induced CS loss was characterized by impaired perceptual template; and (4) self-reported questionnaires indicated that subjects felt less pleasure and more excitement, less comfort and more fatigued by screen light, less comfort in the area around the eye, and serious symptoms such as piercing pain, blur acid, strain, eye burning, and dizziness after HDT. These findings improve our understanding of the negative effects of simulated microgravity on visual function and elucidate the potential risks of astronauts during space flight.

Postural influence on intracranial fluid dynamics: an overview.

This review focuses on the effects of different body positions on intracranial fluid dynamics, including cerebral arterial and venous flow, cerebrospinal fluid (CSF) hydrodynamics, and intracranial pressure (ICP). It also discusses research methods used to quantify these effects. Specifically, the implications of three types of body positions (orthostatic, supine, and antiorthostatic) on cerebral blood flow, venous outflow, and CSF circulation are explored, with a particular emphasis on cerebrovascular autoregulation during microgravity and head-down tilt (HDT), as well as posture-dependent changes in cerebral venous and CSF flow, ICP, and intracranial compliance (ICC). The review aims to provide a comprehensive analysis of intracranial fluid dynamics during different body positions, with the potential to enhance our understanding of intracranial and craniospinal physiology.

Segmental Tissue Resistance of Healthy Young Adults during Four Hours of 6-Degree Head-Down-Tilt Positioning.

(1) Background: One effect of microgravity on the human body is fluid redistribution due to the removal of the hydrostatic gravitational gradient. These fluid shifts are expected to be the source of severe medical risks and it is critical to advance methods to monitor them in real-time. One technique to monitor fluid shifts captures the electrical impedance of segmental tissues, but limited research is available to evaluate if fluid shifts in response to microgravity are symmetrical due to the bilateral symmetry of the body. This study aims to evaluate this fluid shift symmetry. (2) Methods: Segmental tissue resistance at 10 kHz and 100 kHz was collected at 30 min intervals from the left/right arm, leg, and trunk of 12 healthy adults over 4 h of 6° head-down-tilt body positioning. (3) Results: Statistically significant increases were observed in the segmental leg resistances, first observed at 120 min and 90 min for 10 kHz and 100 kHz measurements, respectively. Median increases were approximately 11% to 12% for the 10 kHz resistance and 9% for the 100 kHz resistance. No statistically significant changes in the segmental arm or trunk resistance. Comparing the left and right segmental leg resistance, there were no statistically significant differences in the resistance changes based on the side of the body. (4) Conclusions: The fluid shifts induced by the 6° body position resulted in similar changes in both left and right body segments (that had statistically significant changes in this work). These findings support that future wearable systems to monitor microgravity-induced fluid shifts may only require monitoring of one side of body segments (reducing the hardware needed for the system).

Trendelenburg position for internal jugular vein catheterization: A systematic review and meta-analysis.

To determine the effect of Trendelenburg position on the diameter or cross-section area of the internal jugular vein (IJV) a systematic review and metanalysis was performed. Studies that evaluated the cross-sectional area (CSA) and anteroposterior (AP) diameter of the right internal jugular vein (RIJV) with ultrasonography in supine and any degree of head-down tilt (Trendelenburg position) were analyzed. A total of 22 articles (613 study subjects) were included. A >5° Trendelenburg position statistically increases RIJV CSA and AP diameter. Further inclination from 10° does not statistically benefit IJV size. This position should be recommended for CVC placement, when patient conditions allow it, and US-guided cannulation is not available.

Relationships between common carotid artery blood flow and anesthesia, pneumoperitoneum, and head-down tilt position: a linear mixed-effect analysis.

This study investigated the effects of pneumoperitoneum and the head-down tilt position on common carotid artery (CCA) blood flow in surgical patients. METHODS: This prospective observational study included 20 patients who underwent gynecological surgery. CCA blood flow was measured using Doppler ultrasound at four-time points: awake in the supine position [T1], 3 min after anesthesia induction in the supine position [T2], 3 min after pneumoperitoneum in the supine position [T3], and 3 min after pneumoperitoneum in the head-down tilt position [T4]. Hemodynamic and respiratory parameters were also recorded at each time point. Linear mixed-effect analyses were performed to compare CCA blood flow across the time points and assess its relationship with hemodynamic parameters. RESULTS: Compared with T1, CCA blood flow decreased significantly at T2 (345.4 [288.0-392.9] vs. 293.1 [253.0-342.6], P = 0.048). CCA blood flow were also significantly lower at T3 and T4 compared with T1 (345.4 [288.0-392.9] vs. 283.6 [258.8-307.6] and 287.1 [242.1-321.4], P = 0.005 and 0.016, respectively). CCA blood flow at T3 and T4 did not significantly differ from that at T2. Changes in CCA blood flow were significantly associated with changes in cardiac index and stroke volume index (P = 0.011 and 0.024, respectively). CONCLUSION: CCA blood flow was significantly decreased by anesthesia induction. Inducing pneumoperitoneum, with or without the head-down tilt position, did not further decrease CCA blood flow if the cardiac index remained unchanged. The cardiac index and stroke volume index were significantly associated with CCA blood flow. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT04233177, January 18, 2020).

Lower leg blood pressure decreases while calf external pressure increases with the angulation of the Trendelenburg position in the lithotomy position with calf- and foot-supported leg holders.

Patients who underwent lower abdominopelvic surgeries in the lithotomy position (LP) and the Trendelenburg position (TP) with the leg holder are at risk of developing well leg compartment syndrome (WLCS). However, contributing factors related to the LP with TP associated with WLCS are unknown. This study aimed to investigate the associations between external pressure at the calf in the LPs at different angulations of the TP and physiological characteristics. Eighty-four university students (age, 21.7 ± 0.9; 42 men and 42 women) voluntarily participated in the study. The awake participants were placed in the LPs using the calf- and foot-supported leg holder at 0° (horizontal level), 5°, 10°, and 20° head-down tilts by moving the electric operating table. The peak contact pressure (pCP) was measured at the calf as a representative external pressure using the pressure distribution measurement system BIG-MAT®. Lower leg blood pressure significantly decreased with TP angulation, while calf pCP significantly increased with it at 0°, 5°, 10°, and 20° head-down tilts (39.4 ± 15.2, 46.5 ± 17.7, 47.2 ± 16.9, and 50.3 ± 17.6 mmHg, respectively). The calf pCP with a 10° head-down tilt was correlated positively with the calf total force (P < 0.001) and negatively with the calf contact area (P < 0.001). Blood hypoperfusion due to low lower leg blood pressure secondary to lower leg elevation and head-down tilt, and high calf external pressure due to direct external compression from the leg holder where it is loaded may contribute to WLCS.

Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics.

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t-MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal-level data from three experimental series were combined in a study population of 104 t-MCAO rats (45 in HDT15 group and 59 in flat position group). Co-primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non-ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3 , 95% CI 9.1-54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10-16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5-19.18, p = 0.0002). Mean cerebral perfusion in the non-ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI -1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t-MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non-ischemic areas.

The effect of head-down tilt in experimental acute ischemic stroke.

BACKGROUND: Collateral therapeutics exert a promising protective effect on the outcome of acute ischemic stroke. Cerebral blood flow (CBF) may be modulated by different head positioning. The current study aimed to determine the effect of head-down tilt (HDT) on stroke in a rodent model. METHODS: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was used in this study. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride staining, brain water content, perivascular aquaporin protein-4 (AQP4) localization, pericyte marker platelet-derived growth factor receptor ß (PDGFRß), and CBF velocity were evaluated at 24 h after MCAO/R and HDT treatment. RESULTS: In the rat model of MCAO/R, brain infarct volume and neurological deficit score were significantly alleviated in the -30° and -60° groups compared to those in the lying flat (0°) group. Compared with the 0° group, an increase in CBF velocity was detected in the -30° group through two-photon microscopy imaging at 24 h after MCAO/R. Compared with the SHAM group, a decrease in PDGFRß was observed in both the MCAO/R and HDT treatment (-30°) groups. The integrated optical density of PDGFRß was found to be higher in the HDT treatment (-30°) group than in the MCAO/R group. An impairment in perivascular AQP4 polarity and an increase in brain water content were observed after MCAO/R, which were not exacerbated by HDT treatment (-30°). CONCLUSIONS: Our findings suggest that HDT treatment at certain degrees may exert a neuroprotective effect after MCAO/R through improving CBF velocity and the protection of pericytes.

Are head-down tilt bedrest studies capturing the true nature of spaceflight-induced cognitive changes? A review.

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions.

MRI-based quantification of posterior ocular globe flattening during 60 days of strict 6° head-down tilt bed rest with and without daily centrifugation.

Spaceflight associated neuro-ocular syndrome (SANS) is associated with acquired optic disc edema, hyperopia, and posterior globe flattening in some astronauts during long-duration spaceflight possibly due to the headward fluid redistribution in microgravity. The goal of this study was to assess whether strict head-down tilt (HDT) bed rest as a spaceflight analog would produce globe flattening and whether centrifugation could prevent these changes. Twenty-four healthy subjects separated into three groups underwent 60 days of strict 6° HDT bed rest: one control group with no countermeasure (n = 8) and two countermeasure groups exposed to 30 min daily of short-arm centrifugation as a means of artificial gravity (AG), either intermittent (iAG, n = 8) or continuous (cAG, n = 8). Magnetic resonance images (MRI) were collected at baseline, HDT-day 14, HDT-day 52, and 3 days after bed rest. An automated method was applied to quantify posterior globe volume displacement compared with baseline scans. On average, subjects showed an increasing degree of globe volume displacement with bed rest duration (means ± SE: 1.41 ± 1.01 mm3 on HDT14 and 4.04 ± 1.19 mm3 on HDT52) that persisted post-bed rest (5.51 ± 1.26 mm3). Application of 30 min daily AG did not have a significant impact on globe volume displacement (P = 0.42 for cAG and P = 0.93 for iAG compared with control). These results indicate that strict 6° HDT bed rest produced displacement of the posterior globe with a trend of increasing displacement with longer duration that was not prevented by daily 30 min exposure to AG.NEW & NOTEWORTHY Head-down tilt (HDT) bed rest is commonly used as a spaceflight analog for investigating spaceflight associated neuro-ocular syndrome (SANS). Posterior ocular globe flattening has been identified in astronauts with SANS but until now has not been investigated during HDT bed rest. In this study, posterior ocular globe volume displacement was quantified before, during, and after HDT bed rest and countermeasures were tested for their potential to reduce the degree of globe flattening.