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Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org)., (© The Author(s) 2016.)

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short-term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data-driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data-driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. KEY POINTS: Dynamic cerebral autoregulation is governed by two time constants. The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models. This arterial transit time is approximately 1 s in the brain. The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time. The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Background: Our miniaturized bloodless prime circuit for neonatal cardiopulmonary bypass (CPB) has previously been shown to elicit significantly reduced systemic inflammation. We studied the effects of this circuit on cerebral reperfusion because the pathophysiology of "no-reflow" is believed to have an inflammatory component., Methods: Twenty neonatal piglets were randomized to CPB with miniaturized circuitry using either blood (group 1) or bloodless (group 2) prime. At 18 degrees C, piglets underwent 60 minutes of either (A) deep hypothermic circulatory arrest (DHCA) or (B) continuous low-flow bypass (DHCLF). Analysis of cerebral blood flow (CBF) was undertaken before and after CPB in addition to quantification of circulating tumor necrosis factor-alpha (TNFalpha) and intracerebral TNFalpha messenger RNA (mRNA)., Results: The final hematocrit in group 2 was 22% versus 28% (p < 0.05). The CBF fell in every animal in group 1A, but increased in every animal in group 2A (p < 0.001), despite no overall change in total cardiac output. The use of DHCLF was not associated with pronounced trends in either prime group. Final serum TNFalpha concentrations were significantly higher in group 1B (3166 +/- 843 pg/mL) than group 2B (439 +/- 192 pg/mL; p < 0.05). Irrespective of the CPB strategy used, the use of a blood prime generated significantly higher levels of intracerebral TNFalpha mRNA., Conclusions: We attribute the hyperemic cerebrovascular response to reduced inflammation through avoiding allogeneic whole blood. The analysis of circulating and intracerebral TNFalpha in this study suggests that DHCLF in conjunction with a bloodless prime might offer advantages through avoiding ischemia, no-reflow, and in addition, resulting in a significantly reduced cerebral inflammatory response.

Laser Doppler flowmetry (LDF) is a well-established technique for the investigation of tissue microcirculation. Compared to skin, the use in the human brain is sparse. The measurement of cerebral microcirculation in neurointensive care and during neurosurgery is challenging and requires adaptation to the respective clinical setting. The aim of the review is to present state of the art and progress in neurosurgery and neurointensive care where LDF has proven useful and can find clinical importance in the investigation of cerebral microcirculation. The literature in the field is summarized and recent technical improvements regarding LDF systems and fiber optical probe designs for neurosurgical and neurocritical care described. By combining two signals from the LDF unit, the measurement of the microcirculation (Perfusion) and gray whiteness (TLI) of the brain tissue, the full potential of the device is achieved. For example, a forward-looking LDF-probe detects high-risk hemorrhage areas and gray-white matter boundaries along intraoperative trajectories during stereotactic neurosurgery. Proof of principles are given for LDF as a guidance tool in deep brain stimulation implantation, brain tumor needle biopsies, and as long-term monitoring device in neurocritical care. With well-designed fiber optical probes, surgical fixation, and signal processing for movement reduction, LDF monitoring of the cerebral microcirculation is successful up to 10 days. The use of LDF can be combined with other physiological measurement techniques, for example, fluorescence spectroscopy for identification of glioblastoma during tumor surgery. Fiber optics can also be used during magnetic resonance imaging (MRI). Despite the many advantages, fiber optical LDF has not yet reached its full potential in clinical neuro-applications. Multicenter studies are required to further evaluate LDF in neurosurgery and neurointensive care. In conclusion, the present status of LDF in neurosurgery and neurointensive care has been reviewed. By combining Perfusion and TLI with tailored probe designs the full potential of LDF can be achived in measuring cerebral microcirculation. This includes guidance during DBS implantation and needle biopsies, and long-term monitoring in neurocritical care., (© 2024 The Author(s). Microcirculation published by John Wiley & Sons Ltd.)

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we find the emergence of the cortical hierarchy revealed by the highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increases in a biphasic pattern featured by initial rapid and subsequently slower rate, and break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices are associated with enhanced language and motor skills, and frontoparietal association cortices with cognitive skills. The study discovers emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning., (© 2024. The Author(s).)

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury. IMPACT: NIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO 2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants., Methods: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events., Results: Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters., Conclusions: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations., Impact: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: A simulation-based supervised deep neural network (DNN) can accurately estimate cerebral blood flow (CBF) and arterial transit time (ATT) from multidelay arterial spin labeling signals. However, the performance of deep learning depends on the characteristics of the training data set. We aimed to investigate the effects of the ground truth (GT) ranges of CBF and ATT on the performance of the DNN when training data were prepared using arterial spin labeling signal simulation., Methods: Deep neural networks were individually trained using 36 patterns of the training data sets. Simulation test data (1,000,000 points), 17 healthy volunteers, and 1 patient with moyamoya disease were included. The simulation test data were used to evaluate accuracy, precision, and noise immunity of the DNN. The best-performing DNN was determined by the normalized mean absolute error (NMAE), normalized root mean squared error (NRMSE), and normalized coefficient of variation over repeated training (CV Net ). Cerebral blood flow and ATT values and their histograms were compared between the GT and predicted values. For the in vivo data, the dependency of the predicted values on the GT ranges was visually evaluated by comparing CBF and ATT maps between the best-performing DNN and the other DNNs. Moreover, using the synthesized noisy images, noise immunity was compared between the best-performing DNN based on the simulation study and a conventional method., Results: The simulation study showed that a network trained by the GT of CBF and ATT in the ranges of 0 to 120 mL/100 g/min and 0 to 4500 milliseconds, respectively, had the highest performance (NMAE CBF , 0.150; NRMSE CBF , 0.231; CV NET CBF , 0.028; NMAE ATT , 0.158; NRMSE ATT , 0.257; and CV NET ATT , 0.028). Although the predicted CBF and ATT varied with the GT range of the training data sets, the appropriate settings preserved the accuracy, precision, and noise immunity of the DNN. In addition, the same results were observed in in vivo studies., Conclusions: The GT ranges to prepare the training data affected the performance of the simulation-based supervised DNNs. The predicted CBF and ATT values depended on the GT range; inappropriate settings degraded the accuracy, whereas appropriate settings of the GT range provided accurate and precise estimates., Competing Interests: Please note that there is a conflict of interest, as Naoyuki Takei is an employee of GE Healthcare. The other authors have no potential conflicts of interest with respect to the research of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A simple and inexpensive technique is described for the assessment of regional cerebral blood volume (CBV) using a color reaction based on the pseudoperoxidase activity of hemoglobin. Cryostat sections are placed on a commercially available reagent strip originally designed for quantitative estimation of blood content in urine. After melting of the brain section, a blue color reaction appears which is darker in areas with higher hemoglobin content. The image is analyzed by a computerized image-processing system and evaluated by standards prepared from brain homogenate with different hemoglobin content. From the optical density data, regional CBV is calculated with correction for the difference between microvascular and large vessel hematocrit. The method was validated by a radiolabel procedure. Values of regional CBV are reported in gray matter areas of control rabbits and in brains embolized by autologous clot. This simple inexpensive technique is a useful supplementary tool in multiparametric metabolic studies.

Abstract: Traumatic brain injury (TBI) is associated with increased morbidity and mortality in civilian trauma and battlefield settings. It has been classified across a continuum of dysfunctions, with as much as 80% to 90% of cases diagnosed as mild to moderate in combat casualties. In this report, a framework is presented that focuses on the potential benefits for acute noninvasive treatment of reduced cerebral perfusion associated with mild TBI by harnessing the natural transfer of negative intrathoracic pressure during inspiration. This process is known as intrathoracic pressure regulation (IPR) therapy, which can be applied by having a patient breath against a small inspiratory resistance created by an impedance threshold device. Intrathoracic pressure regulation therapy leverages two fundamental principles for improving blood flow to the brain: (1) greater negative intrathoracic pressure enhances venous return, cardiac output, and arterial blood pressure; and (2) lowering of intracranial pressure provides less resistance to cerebral blood flow. These two effects work together to produce a greater pressure gradient that results in an improvement in cerebral perfusion pressure. In this way, IPR therapy has the potential to counter hypotension and hypoxia, potentially significant contributing factors to secondary brain injury, particularly in conditions of multiple injuries that include severe hemorrhage. By implementing IPR therapy in patients with mild-to-moderate TBI, a potential exists to provide early neuroprotection at the point of injury and a bridge to more definitive care, particularly in settings of prolonged delays in evacuation such as those anticipated in future multidomain operations., Level of Evidence: Report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cerebral autoregulation plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury, which is highly important for patients in the neurological intensive care unit (neuro-ICU). Although the consensus white paper suggests that a minimum of 5 min of data are needed for assessing dynamic cerebral autoregulation with transfer function analysis (TFA), it remains unknown if the length of these data is valid for patients in the neuro-ICU, of whom are notably different than the general populations. We aimed to investigate the effect of data length using transcranial Doppler ultrasound combined with invasive blood pressure measurement for the assessment of dynamic cerebral autoregulation in patients in the neuro-ICU., Methods: Twenty patients with various clinical conditions (severe acute encephalitis, ischemic stroke, subarachnoid hemorrhage, brain injury, cerebrovascular intervention operation, cerebral hemorrhage, intracranial space-occupying lesion, and toxic encephalopathy) were recruited for this study. Continuous invasive blood pressure, with a pressure catheter placed at the radial artery, and bilateral continuous cerebral blood flow velocity with transcranial Doppler ultrasound were simultaneously recorded for a length of 10 min for each patient. TFA was applied to derive phase shift, gain, and coherence function at all frequency bands from the first 2, 3, 4, 5, 6, 7, 8, 9, and 10 min of the 10-min recordings in each patient on both hemispheres. The variability in the autoregulatory parameters in each hemisphere was investigated by repeated measures analysis of variance., Results: Forty-one recordings (82 hemispheres) were included in the study. According to the critical values of coherence provided by the Cerebral Autoregulation Research Network white paper, acceptable rates for the data were 100% with a length ≥ 7 min. The final analysis included 68 hemispheres. The effects of data length on trends in phase shift in the very low frequency (VLF) band (F 1.801,120.669  = 6.321, P = 0.003), in the LF band (F 1.274,85.343  = 4.290, P = 0.032), and in the HF band (F 1.391,93.189  = 3.868, P = 0.039) were significant for 3-7 min, for 4-7 min, and for 5-8 min, respectively. Effects were also significant on the gain in the VLF band (F 1.927,129.134  = 3.215, P = 0.045) for 2-8 min and on the coherence function in all frequency bands (VLF F 2.846,190.671  = 90.247, P < 0.001, LF F 2.515,168.492  = 55.770, P < 0.001, HF F 2.411, 161.542  = 33.833, P < 0.001) for 2-10 min., Conclusions: Considering the acceptable rates for the data and the variation in the TFA variables (phase shift and gain), we recommend recording data for a minimum length of 7 min for TFA in patients in the neuro-ICU., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: Preclinical and non-medicinal interventions are essential for preventing and treating cognitive decline in patients with mild cognitive impairment (MCI). Whole-body vibration (WBV) exercise is conducted on a platform that generates vertical sinusoidal vibrations, and WBV training may improve regional cerebral blood flow (rCBF) and cognitive function, however, the underlying mechanism remains unclear. The aim of the present study was to investigate whether WBV exercise and a 24-week WBV training protocol increased rCBF and enhanced cognitive function in patients with amnestic MCI (aMCI)., Methods: [ 99m Tc]-ECD and SPECT studies were performed on 16 aMCI patients at baseline, during WBV exercise, and on 6 of the 16 patients after 24-week WBV training. To diagnose SPECT images and select the patients, a Z-score mapping approach was used, which revealed pathological hypoperfusion in the parietal association cortex, precuneus and/or posterior cingulate gyrus for MCI at baseline. rCBF was semi-quantitatively measured and underestimation in the high flow range was corrected. Since it is difficult to quantitatively measure rCBF during WBV exercise, the rCBF ratio was obtained by standardizing with the average of individual mean SPECT counts with correcting underestimation in the high flow range. The rCBF ratios at baseline and after WBV training were also obtained in a similar manner. Since the changes in rCBF were regarded as corresponding to the changes in rCBF ratio , the ratios were compared. Cognitive function was also evaluated and compared., Results: We found that the rCBF ratio changed with an average range of 11.5% during WBV exercise, and similar changes were observed after 24-week WBV training with a 13.0% change, resulting in improved cognitive function (MoCA-J, P = 0.028). The rCBF ratio increased in the parietal association cortex and occipital lobes, including the precuneus and posterior cingulate gyrus, at which hypoperfusion was detected at baseline, but decreased in the frontal lobe and anterior cingulate gyrus. The rCBF ratio increased on the right side of several motion-suppressive nuclei by WBV exercise; the bilateral red nuclei and right medial globus pallidus by WBV training., Conclusion: WBV exercise and training increase rCBF in aMCI patients, and WBV training enhances cognitive function and may increase the cognitive reserve. Further investigation is necessary., (© 2021. The Japanese Society of Nuclear Medicine.)

Introduction: To examine the hypothesis that exercise training induces adaptation in cerebrovascular function, we recruited 63 older adults (62 ± 7 yr, 46 females) to undertake 24 wk of either land walking or water walking, or participate in a nonexercise control group. This is the first multi-interventional study to perform a comprehensive assessment of cerebrovascular function in response to longer term (6-month) training interventions, including water-based exercise, in older healthy individuals., Methods: Intracranial blood flow velocities (middle cerebral artery (MCAv) and posterior cerebral artery) were assessed at rest and in response to neurovascular coupling, hypercapnic reactivity, and cerebral autoregulation., Results: We observed no change in resting MCAv in response to either training intervention (pre vs post, mean (95% confidence interval), land walking: 65 (59-70) to 63 (57-68) cm·s-1, P = 0.33; water walking: 63 (58-69) to 61 (55-67) cm·s-1, P = 0.92) compared with controls and no change in neurovascular coupling (land walking: P = 0.18, water walking: P = 0.17). There was a significant but modest improvement in autoregulatory normalized gain after the intervention in the water-walking compared with the land-walking group (P = 0.03). Hypercapnic MCAv reactivity was not different based on exercise group (land: P = 087, water: P = 0.83); however, when data were pooled from the exercise groups, increases in fitness were correlated with decreases in hypercapnic reactivity (r2 = 0.25, P = 0.003)., Conclusions: Although exercise was not associated with systematic changes across multiple domains of cerebrovascular function, our data indicate that exercise may induce modest changes in autoregulation and CO2 reactivity. These findings should encourage further studies of the longer-term implications of exercise training on cerebrovascular health., (Copyright © 2021 by the American College of Sports Medicine.)

Purpose: Sedentary behavior increases the risk for cardiovascular and cerebrovascular disease. To understand potential benefits and underlying mechanisms, we examined the acute and long-term effect of reduced sitting intervention on vascular and cerebrovascular function., Methods: This prospective study included 24 individuals with increased cardiovascular risk (65 ± 5 yr, 29.8 ± 3.9 kg·m-2). Before and after 16-wk reduced sitting, using a mobile health device with vibrotactile feedback, we examined (i) vascular function (flow-mediated dilation [FMD]), (ii) cerebral blood flow velocity (CBFv, transcranial Doppler), and (iii) cerebrovascular function (cerebral autoregulation [CA] and cerebral vasomotor reactivity [CVMR]). To better understand potential underlying mechanisms, before and after intervention, we evaluated the effects of 3 h sitting with and without light-intensity physical activity breaks (every 30 min)., Results: The first wave of participants showed no change in sedentary time (n = 9, 10.3 ± 0.5 to 10.2 ± 0.5 h·d-1, P = 0.87). Upon intervention optimization by participants' feedback, the subsequent participants (n = 15) decreased sedentary time (10.2 ± 0.4 to 9.2 ± 0.3 h·d-1, P < 0.01). This resulted in significant increases in FMD (3.1% ± 0.3% to 3.8% ± 0.4%, P = 0.02) and CBFv (48.4 ± 2.6 to 51.4. ±2.6 cm·s-1, P = 0.02), without altering CA or CVMR. Before and after the 16-wk intervention, 3-h exposure to uninterrupted sitting decreased FMD and CBFv, whereas physical activity breaks prevented a decrease (both P < 0.05). CA and CVMR did not change (P > 0.20)., Conclusion: Long-term reduction in sedentary behavior improves peripheral vascular function and cerebral blood flow and acutely prevents impaired vascular function and decreased cerebral blood flow. These results highlight the potential benefits of reducing sedentary behavior to acutely and chronically improve cardio- or cerebrovascular risk., (Copyright © 2020 by the American College of Sports Medicine.)

Aim: To assess and compare the effects of 160 IU intranasal insulin (IN-INS) administration on regional cerebral blood flow (rCBF) in healthy male individuals with normal weight and overweight phenotypes., Methods: Thirty young male participants (mean age 25.9 years) were recruited and stratified into two cohorts based on body mass index: normal weight (18.5-24.9 kg/m 2 ) and overweight (25.0-29.9 kg/m 2 ). On separate mornings participants received 160 IU of IN-INS using an intranasal protocol and intranasal placebo as part of a double-blind crossover design. Thirty minutes following administration rCBF data were collected using a magnetic resonance imaging method called pseudocontinuous arterial spin labelling. Blood samples were collected to assess insulin sensitivity and changes over time in peripheral glucose, insulin and C-peptide., Results: Insulin sensitivity did not significantly differ between groups. Compared with placebo, IN-INS administration reduced rCBF in parts of the hippocampus, insula, putamen, parahippocampal gyrus and fusiform gyrus in the overweight group. No effect was seen in the normal weight group. Insula rCBF was greater in the overweight group versus normal weight only under placebo conditions. Peripheral glucose and insulin levels were not affected by IN-INS. C-peptide levels in the normal weight group decreased significantly over time following IN-INS administration but not placebo., Conclusion: Insulin-induced changes within key regions of the brain involved in gustation, memory and reward were observed in overweight healthy male individuals. Following placebo administration, differences in gustatory rCBF were observed between overweight and normal weight healthy individuals., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplantation, comparing these brain abnormalities before and after kidney transplantation may identify potential reversibility in ESKD-associated brain abnormalities., Methods: In this study of patients with ESKD and age-matched healthy controls, we used arterial spin labeling to assess the effects of kidney transplantation on cerebral blood flow and magnetic resonance spectroscopic imaging to measure cerebral neurochemical concentrations ( N -acetylaspartate, choline, glutamate, glutamine, myo-inositol, and total creatine). We also assessed white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain magnetic resonance imaging measurements before, 3 months after, and 12 months after transplantation and compared these findings with those of healthy controls., Results: Study participants included 29 patients with ESKD and 19 controls; 22 patients completed post-transplant magnetic resonance imaging. Cerebral blood flow, which was higher in patients pretransplant compared with controls ( P =0.003), decreased post-transplant ( P <0.001) to values in controls. Concentrations of neurochemicals choline and myo-inositol that were higher pretransplant compared with controls ( P =0.001 and P <0.001, respectively) also normalized post-transplant ( P <0.001 and P <0.001, respectively). FA increased ( P =0.001) and MD decreased ( P <0.001) post-transplant., Conclusions: Certain brain abnormalities in CKD are reversible and normalize with kidney transplantation. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted., Clinical Trial Registry Name and Registration Number: Cognitive Impairment and Imaging Correlates in End Stage Renal Disease, NCT01883349., (Copyright © 2021 by the American Society of Nephrology.)

Key Points: Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia., Abstract: Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO 2 (capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO 2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P < 0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70 ± 1.58 (normocapnia) to 4.14 ± 2.05 (hypercapnia; P < 0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies., (© 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

We hypothesized that knowledge of cerebral autoregulation (CA) status during recanalization therapies could guide further studies aimed at neuroprotection targeting penumbral tissue, especially in patients that do not respond to therapy. Thus, we assessed CA status of patients with acute ischemic stroke (AIS) during intravenous r-tPA therapy and associated CA with response to therapy. AIS patients eligible for intravenous r-tPA therapy were recruited. Cerebral blood flow velocities (transcranial Doppler) from middle cerebral artery and blood pressure (Finometer) were recorded to calculate the autoregulation index (ARI, as surrogate for CA). National Institute of Health Stroke Score was assessed and used to define responders to therapy (improvement of ≥ 4 points on NIHSS measured 24-48 h after therapy). CA was considered impaired if ARI < 4. In 38 patients studied, compared to responders, non-responders had significantly lower ARI values (affected hemisphere: 5.0 vs. 3.6; unaffected hemisphere: 5.4 vs. 4.4, p = 0.03) and more likely to have impaired CA (32% vs. 62%, p = 0.02) during thrombolysis. In conclusion, CA during thrombolysis was impaired in patients who did not respond to therapy. This variable should be investigated as a predictor of the response to therapy and to subsequent neurological outcome.

Purpose: Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope., Methods: The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt., Results: At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge., Conclusions: Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

Key Points: Dynamic cerebral autoregulation (CA) is expressed by the temporal pattern of cerebral blood flow (CBF) recovery following a sudden change in arterial blood pressure (BP). Transfer function analysis of BP as input and CBF velocity as output can express dynamic CA through its amplitude (or gain) and phase frequency responses. The upper frequency limit (F upLim ) at which dynamic CA can operate is of considerable physiological interest and can also provide additional information about worsening CA due to disease processes. In healthy subjects F upLim was strongly dependent on arterial P C O 2 changes induced by four different breathing manoeuvres. The considerable intersubject variability in F upLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in studies of dynamic CA., Abstract: Dynamic cerebral autoregulation (CA) can be expressed in the frequency domain by the amplitude and phase frequency responses calculated by transfer function analysis of arterial blood pressure (BP) and cerebral blood flow velocity (CBFV). We studied the effects of arterial P C O 2 ( P aC O 2 ) on the upper frequency limit (F upLim ) of these responses and its intersubject variability. Twenty-four healthy subjects (11 female, age 36.0 ± 13.4 years) were recruited. Recordings of CBFV (transcranial Doppler ultrasound), BP (Finometer) and end-tidal CO 2 ( P ETC O 2 , capnography) were performed during 5 min at rest (normocapnia) and during four breathing manoeuvres: 5% and 8% CO 2 in air and hyperventilation targeting reductions of 5 and 10 mmHg compared to normocapnia. F upLim was determined by the break point of the autoregulation index (ARI) curve as a function of frequency when the phase response was gradually set to zero. The five breathing conditions led to highly significant differences in P ETC O 2 (p < 0.0001), CBFV (P < 0.0001), ARI (p < 0.0001) and F upLim (p < 0.0001). F upLim ranged from 0.167 ± 0.036 Hz at the lowest values of hypocapnia (28.1 ± 1.9 mmHg) to 0.094 ± 0.040 Hz at the highest level of hypercapnia (41.7 ± 5.4 mmHg), showing a correlation of r = -0.53 (p < 0.001) with P ETC O 2 . These findings reinforce the key role of P aC O 2 in CBF regulation. The considerable intersubject variability of F upLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in dynamic CA studies, and that the higher frequency band (0.20-0.40 Hz), in particular, does not contain relevant information about dynamic CA. Further investigations are needed to assess the information value of F upLim as a marker of dynamic CA efficiency in physiological and clinical studies., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

New Findings: What is the central question of this study? Does habitual resistance and endurance exercise modify dynamic cerebral autoregulation? What is the main finding and its importance? To the authors' knowledge, this is the first study to directly assess dynamic cerebral autoregulation in resistance-trained individuals, and potential differences between exercise training modalities. Forced oscillations in blood pressure were induced by repeated squat-stands, from which dynamic cerebral autoregulation was assessed using transfer function analysis. These data indicate that dynamic cerebral autoregulatory function is largely unaffected by habitual exercise type, and further document the systemic circulatory effects of regular exercise., Abstract: Regular endurance and resistance exercise produce differential but desirable physiological adaptations in both healthy and clinical populations. The chronic effect of these different exercise modalities on cerebral vessels' ability to respond to rapid changes in blood pressure (BP) had not been examined. We examined dynamic cerebral autoregulation (dCA) in 12 resistance-trained (mean ± SD, 25 ± 6 years), 12 endurance-trained (28 ± 9 years) and 12 sedentary (26 ± 6 years) volunteers. The dCA was assessed using transfer function analysis of forced oscillations in BP vs. middle cerebral artery blood velocity (MCAv), induced via repeated squat-stands at 0.05 and 0.10 Hz. Resting BP and MCAv were similar between groups (interaction: both P ≥ 0.544). The partial pressure of end-tidal carbon dioxide ( P ETC O 2 ) was unchanged (P = 0.561) across squat-stand manoeuvres (grouped mean for absolute change +0.6 ± 2.3 mmHg). Gain and normalized gain were similar between groups across all frequencies (both P ≥ 0.261). Phase showed a frequency-specific effect between groups (P = 0.043), tending to be lower in resistance-trained (0.63 ± 0.21 radians) than in endurance-trained (0.90 ± 0.41, P = 0.052) and -untrained (0.85 ± 0.38, P = 0.081) groups at slower frequency (0.05 Hz) oscillations. Squat-stands induced mean arterial pressure perturbations differed between groups (interaction: P = 0.031), with greater changes in the resistance (P < 0.001) and endurance (P = 0.001) groups compared with the sedentary group at 0.05 Hz (56 ± 13 and 49 ± 11 vs. 35 ± 11 mmHg, respectively). The differences persisted at 0.1 Hz between resistance and sedentary groups (49 ± 12 vs. 33 ± 7 mmHg, P < 0.001). These results indicate that dCA remains largely unaltered by habitual endurance and resistance exercise with a trend for phase to be lower in the resistance exercise group at lower fequencies., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

The beneficial effects of transcranial direct current stimulation (tDCS) for stroke rehabilitation are limited by the variability in changes in corticomotor excitability (CME) after tDCS. Neuronal activity is closely related to cerebral blood flow; however, the cerebral hemodynamics of neuromodulation in relation to neural effects have been less explored. In this study, we examined the effects of tDCS on cerebral blood velocity (CBv) in chronic stroke survivors using transcranial Doppler (TCD) ultrasound in relation to changes in CME and described the neurovascular characteristics of tDCS responders. Middle cerebral artery (MCA) CBv, cerebrovascular resistance (CVRi) and other cerebral hemodynamics-related variables were continuously measured before and after 15 min of 1 mA anodal tDCS to the lesioned lower limb M1. tDCS did not modulate CBv in the whole group and upon TMS-based stratification of responders and non-responders. However, at baseline, responders demonstrated lower CME levels, lower CBv and higher CVRi as compared to non-responders. These results indicate a possible difference in baseline CME and CBv in tDCS responders that may influence their response to neuromodulation. Future trials with a large sample size and repeated baseline measurements may help validate these findings and establish a relationship between neuromodulation and neurovascular mechanisms in stroke.

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO 2 ) monitors., Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8 h of daily monitoring. Brain PbO 2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO 2 below 19 mmHg for more than 6 min from baseline (PbO 2  > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21 mmHg) and "low" (< 19 mmHg) PbO 2 . Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension., Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO 2 , we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO 2 epochs (AUC 0.876)., Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

Brain vascular health worsens with age, as is made evident by resting grey matter cerebral blood flow (CBF GM ) reductions and lengthening arterial transit time (ATT GM ). Exercise training can improve aspects of brain health in older adults, yet its effects on CBF GM and ATT GM remain unclear. This randomised controlled trial assessed responses of CBF GM and ATT GM to a 26 week exercise intervention in 65 healthy older adults (control: n = 33, exercise: n = 32, aged 60-81 years), including whether changes in CBF GM or ATT GM were associated with changes in cognitive functions. Multiple-delay pseudo-continuous arterial spin labelling data were used to estimate resting global and regional CBF GM and ATT GM . Results showed no between-group differences in CBF GM or ATT GM following the intervention. However, exercise participants with the greatest cardiorespiratory gains (n = 17; ∆V̇O 2peak >2 mL/kg/min) experienced global CBF GM reductions (-4.0 [-7.3, -0.8] mL/100 g/min). Cognitive functions did not change in either group and changes were not associated with changes in CBF GM or ATT GM . Our findings indicate that exercise training in older adults may induce global CBF GM reductions when high cardiorespiratory fitness gains are induced, but this does not appear to affect cognitive functions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katrien Segaert reports financial support was provided by the Research Council of Norway. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF., Competing Interests: Declaration of competing interest Elizabeth A.V. Jones reports financial support was provided by Horizon Europe. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To compare the effect of moderate-intensity aquatic treadmill exercise (ATM) on cerebral blood flow (CBF) and cognitive function in healthy older adults to that of moderate-intensity land-based treadmill exercise (LTM). This randomized controlled trial study was conducted between May 2023 and Oct 2023. Twenty-eight participants aged 60-80 were randomly assigned to either ATM group (N = 14) or LTM group (N = 14). Cognitive function and cerebral blood flow were assessed before and after the exercise. The outcome measures used in this study were the Digit Symbol Substitution Test (DSST) and the Digit Span Test (DST) to assess cognitive performance, and the mean middle cerebral artery blood velocity (MCAvmean) to evaluate CBF. A mixed effects model was used to analyze the within-group and between-group differences in cognitive function and CBF outcomes pre-to-post treadmill by SPSS. The DSST demonstrated a statistically significant improvement within both the ATM [β ± SE: -13.643 ± 2.407, 95 % CI: -18.749, -8.537] and LTM [β ± SE: -19.25 ± 3.66, 95 % CI: -26.424, -12.076] groups, indicating clinical significance in both groups. Both ATM and LTM groups exhibited post-exercise improvements within their respective groups for forward Digit Span Test (FDST) [ATM β ± SE: -0.143 ± 0.362, 95 % CI: -0.92, 0.634; LTM β ± SE: -0.286 ± 0.37, 95 % CI: -1.078, 0.506] and backward Digit Span Test (BDST) (ATM β ± SE: -1.741 ± 5.377, 95 % CI: -13.27, 9.792; LTM β ± SE: -6.729 ± 5.370, 95 % CI: -4.788, 18.24). In terms of MCAv mean , there is a higher improvement of CBF in ATM group [β ± SE: -138.669 ± 67.9217, 95 % CI: -288.164, 10.826] than LTM group [β ± SE: -9.305 ± 70.076, 95 % CI: -153.617, 135.007]. Hence, a single bout of moderate-intensity ATM and LTM can enhance cognitive function and CBF in healthy older adults, suggesting their potential as preventive strategies against age-related declines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter Smielewski and Marek Czosnyka receive part of the licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge, Cambridge.

Purpose: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE)., Methods: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE., Results: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups., Conclusion: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Although ischemia-reperfusion (I/R) injury varies between cortical and subcortical regions, its effects on specific regions remain unclear. In this study, we used various magnetic resonance imaging (MRI) techniques to examine the spatiotemporal dynamics of I/R injury within the salvaged ischemic penumbra (IP) and reperfused ischemic core (IC) of a rodent model, with the aim of enhancing therapeutic strategies by elucidating these dynamics., Materials and Methods: A total of 17 Sprague-Dawley rats were subjected to 1 h of transient middle cerebral artery occlusion with a suture model. MRI, including diffusion tensor imaging (DTI), T2-weighted imaging, perfusion-weighted imaging, and T1 mapping, was conducted at multiple time points for up to 5 days during the I/R phases. The spatiotemporal dynamics of blood-brain barrier (BBB) modifications were characterized through changes in T1 within the IP and IC regions and compared with mean diffusivity (MD), T2, and cerebral blood flow., Results: During the I/R phases, the MD of the IC initially decreased, normalized after recanalization, decreased again at 24 h, and peaked on day 5. By contrast, the IP remained relatively stable. Both the IP and IC exhibited hyperperfusion, with the IP reaching its peak at 24 h, followed by resolution, whereas hyperperfusion was maintained in the IC until day 5. Despite hyperperfusion, the IP maintained an intact BBB, whereas the IC experienced persistent BBB leakage. At 24 h, the IC exhibited an increase in the T2 signal, corresponding to regions exhibiting BBB disruption at 5 days., Conclusions: Hyperperfusion and BBB impairment have distinct patterns in the IP and IC. Quantitative T1 mapping may serve as a supplementary tool for the early detection of malignant hyperemia accompanied by BBB leakage, aiding in precise interventions after recanalization. These findings underscore the value of MRI markers in monitoring ischemia-specific regions and customizing therapeutic strategies to improve patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This review paper explores the critical role of vascular ion channels in the regulation of cerebral artery function and examines the impact of Alzheimer's disease (AD) on these processes. Vascular ion channels are fundamental in controlling vascular tone, blood flow, and endothelial function in cerebral arteries. Dysfunction of these channels can lead to impaired cerebral autoregulation, contributing to cerebrovascular pathologies. AD, characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles, has been increasingly linked to vascular abnormalities, including altered vascular ion channel activity. Here, we briefly review the role of vascular ion channels in cerebral blood flow control and neurovascular coupling. We then examine the vascular defects in AD, the current understanding of how AD pathology affects vascular ion channel function, and how these changes may lead to compromised cerebral blood flow and neurodegenerative processes. Finally, we provide future perspectives and conclusions. Understanding this topic is important as ion channels may be potential therapeutic targets for improving cerebrovascular health and mitigating AD progression., (© 2024 The Author(s). Microcirculation published by John Wiley & Sons Ltd.)

Background and Objective: Predicting post-operative flow is essential for assessing the risk of adverse events in cerebrovascular stenosis patients following endovascular treatment (EVT). This study aimed to evaluate the accuracy of the CFD simulation model in predicting post-operative velocity, flow and pressure distal to a stenosis, based on cerebrovascular microcirculatory resistance., Methods: The patient-specific models of the extracranial and intracranial arteries were reconstructed. The cerebrovascular microcirculatory resistance was applied to estimate post-operative blood velocity and flow rates. Pearson correlation and Bland-Altman analyses were used to evaluate the correlation and agreement between CFD calculations and transcranial Doppler (TCD) measurements., Results: There was a strong correlation between CFD- and TCD-based mean velocities (r = 0.7733; P = 0.0002), with volume flow measured by both methods also showing robust correlation (r = 0.8621; P < 0.0001). Additionally, agreement was found between mean velocities determined by CFD simulation and those estimated by TCD (P = 0.2446, mean difference -4.2089; limits of agreement -11.5764 to 3.1586). However, agreement between volume flow from CFD simulations and TCD was less consistent (P = 0.0387, mean difference -0.3272, limits of agreement -0.9276 to 0.2731)., Conclusions: The computational method used in this study enables the prediction of hemodynamic changes and offers valuable support in tailoring treatment strategies for cerebrovascular stenosis lesions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: The oxygen extraction fraction is an essential biomarker for the assessment of brain metabolism. A recently proposed method combined with quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude enables noninvasive mapping of the oxygen extraction fraction. Our study investigated the oxygen extraction fraction mapping variations of single-delay and multi-delay arterial spin-labeling., Materials and Methods: A total of twenty healthy participants were enrolled. The multi-echo spoiled gradient-echo, multi-delay arterial spin-labeling, and magnetization-prepared rapid gradient echo sequences were acquired at 3.0 T. The mean oxygen extraction fraction was generated under a single delay time of 1780 ms, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume. The results were compared via paired t tests and the Wilcoxon test. Linear regression analyses were used to investigate the relationships among the oxygen extraction fraction, cerebral blood flow, and venous cerebral blood volume., Results: The oxygen extraction fraction estimate with multi-delay arterial spin-labeling yielded a significantly lower value than that with single-delay arterial spin-labeling. The average values for the whole brain under single-delay arterial spin-labeling, multi-delay arterial spin-labeling of transit-corrected cerebral blood flow, and multi-delay arterial spin-labeling of arterial cerebral blood volume were 41.5 ± 1.7 % (P < 0.05), 41.3 ± 1.9 % (P < 0.001), and 40.9 ± 1.9 % (N = 20), respectively. The oxygen extraction fraction also showed a significant inverse correlation with the venous cerebral blood volume under steady-state conditions when multi-delay arterial spin-labeling was used (r = 0.5834, p = 0.0069)., Conclusion: These findings suggest that the oxygen extraction fraction is significantly impacted by the arterial spin-labeling methods used in the quantitative susceptibility mapping plus the quantitative blood oxygen level-dependent model, indicating that the differences should be accounted for when employing oxygen extraction fraction mapping based on this model in diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Cerebral blood perfusion (CBP) reduction is a prevalent complication following subarachnoid hemorrhage (SAH) in clinical practice, often associated with long-term cognitive impairment and prognosis. Electroacupuncture (EA), a widely utilized traditional Chinese therapy for central nervous system disorders, has demonstrated promising therapeutic effects. This study aims to investigate the therapeutic potential of EA in restoring CBP in SAH rats and to explore the mechanisms involving HIF-1α in this process., Methods: Rats were randomly assigned to one of five groups, including Sham, SAH, EA, EA + Saline, and EA + dimethyloxallyl glycine (DMOG) groups. EA treatment was administered for 10 min daily, while DMOG were intraperitoneally injected. Behavioral tests, cerebral blood flow monitoring, vascular thickness measurement, western blotting, and immunofluorescence staining were conducted to assess the therapeutic effects of EA on cerebral blood flow., Results: SAH resulted in elevated levels of HIF-1α, endothelin (ET), ICAM-1, P-SELECTIN, E-SELECTIN, and decreased level of eNOS in the brain. This led to cerebral vasospasm, decreased CBF, and cognitive deficits in the rat SAH model. EA intervention downregulated the expression of HIF-1α, ET, ICAM-1, P-SELECTIN, and E-SELECTIN, while increasing eNOS expression. This alleviated cerebral vasospasm, restored CBF, and improved cognitive function. However, the administration of the HIF-1α stabilizer (DMOG) counteracted the therapeutic effects of EA., Conclusion: EA promotes the recovery of cerebral blood flow after SAH injury, attenuates cerebral vasospasm, and accelerates the recovery of cognitive dysfunction, and its mechanism of action may be related to the inhibition of the HIF-1α signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Early mobilization benefits critically ill patients, but concerns persist, especially in neurologic intensive care unit patients with acute brain injuries. This study assesses early mobility's impact on cerebrovascular autoregulation (CA) and systemic hemodynamics., Methods: This single-center retrospective study focused on adult neurologic intensive care unit patients undergoing passive cycle ergometry. Data were collected from December 2020 to April 2022. Physical therapists conducted sessions using a standardized protocol, monitoring mean arterial blood pressure (MAP) and intracranial pressure (ICP). The Pressure Reactivity Index (PRx) was calculated as a measure of CA. Statistical analysis included mixed models and repeated measures ANOVA., Results: Eleven patients undergoing continuous physiologic monitoring and early mobility were included, primarily with subarachnoid hemorrhage or intracranial hemorrhage. Median time to protocol initiation was 4 days, with two patients discontinuing due to hemodynamic disturbances. Over a total of 11-hours of neuromonitoring data, passive cycling demonstrated a significant reduction in heart rate (HR), MAP, and ICP across different rotations per minute (RPM) settings compared to baseline. No significant alterations in PRx or cerebral perfusion pressure (CPP) were noted at various RPM levels. However, a significant difference in PRx emerged between patients who completed the protocol and those who did not, particularly at 10 RPM., Discussion: This study offers preliminary insights into the impact of early mobility on CA in acute brain injured patients. While passive cycling demonstrates promise in preserving cerebral hemodynamics, its tolerability may not be uniform across all brain-injured patients. These findings highlight the need to determine optimal early mobilization timing and intensity in this population, emphasizing the necessity for larger prospective studies to validate these findings and inform clinical practice., Details: This manuscript complies with all instructions to the authors. All coauthors meet the authorship requirements and have reviewed and approved the contents of the manuscript. The manuscript has not been published totally or partly, accepted for publication, or under editorial review for publication elsewhere. We have no conflicts of interest to disclose. STROBE checklist was reviewed prior to the submission of this paper. The manuscript adheres to ethical guidelines and was approved by Cleveland Clinic's institutional research board for retrospective study. There is no funding to disclose for this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)