Modulation Of Blood Flow Research Articles

KATP channel–dependent electrical signaling links capillary pericytes to arterioles during neurovascular coupling

The brain has evolved mechanisms to dynamically modify blood flow, enabling the timely delivery of energy substrates in response to local metabolic demands. Several such neurovascular coupling (NVC) mechanisms have been identified, but the vascular signal transduction and transmission mechanisms that enable dilation of penetrating arterioles (PAs) remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of NVC. Recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the diameter of upstream vessels. Thin-strand pericyte cell bodies and processes cover around 90% of the capillary bed, and here we show that these cells play a central role in sensing neural activity and generating and relaying electrical signals to arterioles. We identify a KATP channel-dependent neurovascular signaling pathway that is explained by the recruitment of thin-strand pericytes and we deploy vascular optogenetics to show that currents generated in individual thin-strand pericytes are sent over long distances to upstream arterioles to cause dilations in vivo. Genetic disruption of vascular KATP channels reduces the arteriole diameter response to neural activity and laser ablation of thin-strand pericytes eliminates the KATP-dependent component of NVC. Together, our findings indicate that thin-strand pericytes sense neural activity and transform this into KATP channel-dependent electrometabolic signals that inform upstream arterioles of local energy needs, promoting spatiotemporally precise energy distribution.

Microglia modulate cerebral blood flow and neurovascular coupling through ectonucleotidase CD39.

Microglia and the border-associated macrophages (BAMs) contribute to the modulation of cerebral blood flow (CBF), but the mechanisms have remained ill-defined. Here, we show that microglia regulate the CBF baseline and upsurges after whisker stimulation or intracisternal magna injection of adenosine triphosphate (ATP). Genetic or pharmacological depletion of microglia reduces the activity-dependent hyperemia but not the cerebrovascular responses to adenosine stimulation. Notably, microglia repopulation corrects these CBF reactivity deficits. The microglial-dependent regulation of CBF requires the ATP-sensing P2ry12 receptor and the ectonucleotidase CD39 that initiates the breakdown of extracellular ATP. Pharmacological inhibition or microglia-specific deletion of CD39 simulates the CBF anomalies detected in microglia-deficient mice and reduces the rise of extracellular adenosine after whisker stimulation. Together, these results suggest that the microglial CD39-initiated conversion of extracellular ATP to adenosine is an important step in neurovascular coupling and the regulation of cerebrovascular reactivity.

Blood flow modulation to improve motor and neurophysiological outcomes in individuals with stroke: a scoping review.

Ischemic Conditioning (IC) is a procedure involving brief periods of occlusion followed by reperfusion in stationary limbs. Blood Flow Restriction with Exercise (BFR-E) is a technique comprising blood flow restriction during aerobic or resistance exercise. Both IC and BFR-E are Blood Flow Modulation (BFM) strategies that have shown promise across various health domains and are clinically relevant for stroke rehabilitation. Despite their potential benefits, our knowledge on the application and efficacy of either intervention in stroke is limited. This scoping review aims to synthesize the existing literature on the impact of IC and BFR-E on motor and neurophysiological outcomes in individuals post-stroke. Evidence from five studies displayed enhancements in paretic leg strength, gait speed, and paretic leg fatiguability after IC. Additionally, BFR-E led to improvements in clinical performance, gait parameters, and serum lactate levels. While trends toward motor function improvement were observed post-intervention, statistically significant differences were limited. Neurophysiological changes showed inconclusive results. Our review suggests that IC and BFR-E are promising clinical approaches in stroke, however high-quality studies focusing on neurophysiological mechanisms are required to establish the efficacy and underlying mechanisms of both in stroke. Recommendations regarding future directions and clinical utility are provided.

Regulation of Cerebral Blood Flow Velocity by Transcutaneous Electrical Nerve Stimulation: A Preliminary Study

Objectives: An excessive and abrupt increase in cerebral blood flow may cause blood vessel damage, leading to stroke. Therefore, appropriate methods to immediately regulate blood flow velocity are important. Through an analysis of 31 healthy adults, we therefore investigated whether stimulating the common carotid artery (CCA) using transcutaneous electrical nerve stimulation (TENS) could modulate blood flow velocity in the CCA. Methods: Three stimulation intensities (below-threshold, threshold, and above-threshold) were applied in a random order. Blood velocity changes were examined by the measurement of peak systolic velocity (PSV) with Doppler ultrasound before, during, and after TENS stimulation. To evaluate arterial stiffness, pulse wave velocity (PWV) was calculated using CCA diameter, and blood pressure was measured before and after stimulation. Results: PSV changes in the below-threshold level were significant (p = 0.028). The PSV after below-threshold stimulation was significantly decreased by 2.23% compared to that before stimulation (p = 0.031). PWV showed no significant differences; however, a nonsignificant increase was observed immediately after stimulation only in the above-threshold condition. Above-threshold stimulation can increase vascular tone by activating the sympathetic nerve, possibly triggering vasoconstriction. Conclusions: A decrease in blood flow velocity may not be expected upon the above-threshold stimulation. In contrast, the below-threshold stimulation immediately reduces blood flow velocity, without significantly affecting hemodynamic function, such as arterial flexibility. Therefore, this short-term and low electrical stimulation technique can help to lower vascular resistance and prevent vascular damage from rapid blood flow velocity.

Influence of physical activity on the values of hemorheological parameters

Physical activity is a major factor contributing to maintaining overall health and properly functioning circulatory system. One of the underlying mechanisms is modifying blood flow by influencing hemorheological parameters, the most important of which are: hematocrit, plasma viscosity, whole blood viscosity, the ability of red blood cells to aggregate, deform and orient. We conducted a literature review to investigate how different types, intensities and phases of physical activity affect rheological properties of blood. The results show that short-term effects of exercise differ from the long-term consequences and rheology of blood varies depending on strength/endurance type of the training as good as on its regularity and intensity. Findings from this research may be applicable in improving sport’s performance and health maintenance in athletes.

Arterial Spin Labeling (ASL) MRI in Evaluating Pancreatic Blood Perfusion in Subjects With Different Glucose Tolerances.

The pancreas plays a central role in type 2 diabetes mellitus (T2DM), and its blood flow is usually associated with insulin release demand. To noninvasively assess pancreatic blood flow (PBF) changes and modulation in people with different glucose tolerance following a glucose challenge using ASL MRI. Prospective. Fourteen prediabetes, 22 T2DM, and 40 normal. Pseudo-continuous ASL with a turbo gradient spin echo sequence at 3.0 T. All normal and subjects (diagnosed by oral glucose tolerance test) underwent ASL after fasting for at least 6 hours. The normal and prediabetes groups additionally had ASL scans at 5, 10, 15, 20, and 25 minutes following oral glucose (50 mL, 5%). PBF maps were generated from the ASL data and measured at body and tail. The ability of baseline PBF (BL-PBF) of body, tail (BL-PBFtail), and their average to determine abnormal glucose tolerance and stage was assessed. ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, paired sample t-test, intra-class correlation coefficient, repeated measures ANOVA, correlation analysis, receiver operating characteristic analysis, and logistic regression analysis. A P value <0.05 was considered significant. There were significant differences in BL-PBF among the three groups. The prediabetes group exhibited significantly lower PBF than the normal group at all time points; Both groups showed similar changing trends in PBF (peaking at the 15th minute and subsequently declining). The BL-PBFtail had the highest diagnostic performance when evaluating abnormal glucose tolerance or stage (area under the curves = 0.800, 0.584, respectively) and was an independent risk factor for glucose tolerance status. ASL can noninvasively assess changes in PBF among individuals with varying glucose tolerance and in response to glucose challenge, which could be linked to insulin release demand and might help characterize changes in pancreatic endocrine function. 2 TECHNICAL EFFICACY: Stage 1.

Human Endometrial Pericytes: A Comprehensive Overview of Their Physiological Functions and Implications in Uterine Disorders.

Pericytes are versatile cells integral to the blood vessel walls of the microcirculation, where they exhibit specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, and maintaining homeostasis and are involved in the tissue repair process. The human endometrium is a unique and complex tissue that serves as a natural scar-free healing model with its cyclical repair and regeneration process every month. The regulation of pericytes has gained increasing attention due to their involvement in various physiological and pathological processes. However, endometrial pericytes are less well studied compared to the pericytes in other organs. This review aims to provide a comprehensive overview of endometrial pericytes, with a focus on elucidating their physiological function and potential implications in uterine disorders.

The effect of heart rate variability on the choroidal vascularity of the optical coherence tomography and angiography in central serous chorioretinopathy.

To investigate the correlation between the autonomic nervous system and choroidal vascularity in patients with central serous chorioretinopathy (CSC), using heart rate variability (HRV) analysis, optical coherence tomography (OCT) and OCT angiography (OCTA). We retrospectively analyzed data of 25 patients with unilateral CSC (50 eyes, including the unaffected fellow eyes) and 25 healthy controls. The assessment involved a 5-minute HRV analysis encompassing both frequency and time domains, especially low frequency (LF), high frequency (HF), and LF/HF ratio. In OCT (12 × 9mm) and en-face OCTA (3 × 3mm) scans, we measured parameters including choroidal vascularity index (CVI), choroidal vessel density in the middle and deep layers, and choriocapillaris flow void. Regression analysis was conducted to elucidate the associations between HRV parameters and OCT/OCTA measurements. Normalized LF(LFnorm) and LF/HF ratios were higher in patients with CSC than in healthy controls. LFnorm and the log-transformed ratio of LF to HF [log(LF/HF)] demonstrated a significant and borderline correlation with CVI in the linear regression analysis (P = 0.040, R2 = 0.171, and P = 0.059, R2 = 0.147, respectively). Both CVI and deep choroid vessel density showed a more significant association with LFnorm and log (LF/HF) in the non-linear quadratic regression analysis than in the linear analysis (all, P < 0.04, R2 > 0.25). The frequency-domain parameters of HRV, including LFnorm and log (LF/HF), demonstrated a significant association with indicators reflective of large choroidal vessel luminal area on macular OCT/OCTA scans. This observation implies complicated modulation of choroidal blood flow by the autonomic nervous system in CSC.

Analysis of the Pulpal Blood Flow Microdynamics during Prosthetic Tooth Preparation Using Diamond Burs with Different Degrees of Wear.

Pulpal modifications taking place during prosthetic tooth preparation using worn-out burs may represent a risk for the vitality of the dental pulp. The aim of this in vivo study was to evaluate whether the wear of diamond burs has an influence on the vascular microdynamics at the level of the dental pulp, during vertical preparation for zirconia crowns. The study was performed with a split-mouth design and included 32 vital permanent monoradicular teeth (20 maxillary and 12 mandibular), from six subjects, aged between 20 and 50 years. The teeth were randomly assigned to two study groups of 16 teeth each. For prosthetic preparation, new burs were used in the first group, and burs at their 5th use were used in the second group. Four consecutive determinations of the pulpal blood flow by Laser Doppler flowmetry (LDF-laser Doppler MoorLab instrument VMS-LDF2, Moor Instruments Ltd., Axminster, UK) were taken for each tooth included in the study: before the preparation (control values), immediately, at 24 h, and at 7 days after the prosthetic preparation. A four-way ANOVA statistical analysis was applied to analyze the effect of four considered factors (bur wear degree, time of measurement, tooth number, and tooth location) on the pulpal blood flow (PBF). A significant increase in pulpal blood flow compared to the baseline was recorded immediately after preparation (p < 0.01), at 24 h (p < 0.01), and at 7 days (p < 0.05) in both groups, but more pronounced in the case of burs at the 5th use. The blood flow was significantly higher in upper jaw teeth, irrespective of the measurement time. In conclusion, the use of worn-out diamond burs produces lasting modifications in the pulpal blood flow of teeth that undergo prosthetic crown preparation. ISRCTN registry: ISRCTN49594720.

#1189 Сorrelations between laser doppler flowmetry spectral indicators and glycated hemoglobin level in patients with diabetic nephropathy

Abstract Background and Aims Diabetic microangiopathy is a specific vascular complication of diabetes mellitus type 2, which matters to patients' mortality and individual prognosis. Therefore, an important problem is the development of non-invasive methods for the diagnosis of diabetic microangiopathy, such as laser Doppler flowmetry (LDF). This work aimed to analyze some correlations between LDF spectral indicators and the level of glycated hemoglobin in patients with chronic kidney disease and type 2 diabetes. Method The study included 55 patients (26 men and 29 women) with type 2 diabetes mellitus. The age of patients was 58-77 years. The duration of diabetes was more than 5 years. All patients had chronic kidney disease (stage C3-C4) caused by diabetic nephropathy. For Laser Doppler flowmetry we used the “LDF 100C” system (“Biopac Instruments”, USA). Each patient had a 10-minute LDF registration on the skin of the rear of the foot. Using the special software, we have assessed slow, respiratory and pulse flux motion contribution and flux motion index. The next step was a correlation analysis with the glycated hemoglobin level. Results There were several correlations of the spectral LDF indicators with the level of glycated hemoglobin (Table 1). Thus, a negative correlation with the level of glycated hemoglobin was observed for the flux motion index (p=0.04) and the contribution of slow flux motion (p=0.03). On the contrary, for the contribution of pulse flux motion, there was detected a positive correlation with the level of glycated hemoglobin (p&amp;lt;0.01) (Fig. 1). Conclusion Correlations of LDF indicators with the level of glycated hemoglobin can be explained with the correlation of the diabetic microangiopathy progression with the effectiveness of glycemic control. Hyperglycemia is a key pathogenic factor of type 2 diabetes mellitus and its complications. Consequently, in patients with ineffective or less effective glycemic control, a more significant development of diabetic microangiopathy should be expected. An increase in the contribution of pulse flux motion in the laser Doppler flowmetry use guidelines is regarded as an increase in the role of the pulse wave in microcirculatory blood flow modulation. The cause of the latter is most likely a more intensive remodeling of the walls of arterioles against the background of a higher frequency of hyperglycemia episodes. The negative correlation of the contribution of slow flux motion can be explained by a violation of the local mechanisms of microcirculation modulation. The cause of this disorder is the morphofunctional restructuring of the microvessels themselves, the defeat of smooth myocytes in the wall of arterioles and venules, including pacemaker cells, with a violation of the automatic contractile activity of smooth myocytes, as well as endothelial. These factors lead to a shift in the balance of regulation towards systemic factors, which is reflected in the decrease of the flux motion index. A decrease in the flux motion index is regarded as a microcirculation deficiency, which was detected in all patients with type 2 diabetes mellitus. Thus, correlations of the spectral LDF indicators with the level of glycated hemoglobin corresponds to modern ideas about the pathogenesis of diabetic microangiopathy in type 2 diabetes mellitus. These data can be an additional argument in favor of the further development of improving laser Doppler flowmetry using for the tasks of non-invasive diagnosis of microvascular disorders in patients with type 2 diabetes mellitus. The reported study was funded by RFBR, project number 19-315-90080.

The role of the cardiac vagus in maintaining cardiac function during exercise

There is a strong association between parasympathetic nervous system activity (vagal tone) and physical fitness. High vagal tone is associated with increased capacity to exercise and overall cardiovascular health. Evidence for vagal withdrawal during exercise comes from historic studies examining heart rate control and the use of cholinergic blockers. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via neurotransmitters other than acetylcholine. The left cardiac vagal branch was identified in anesthetized open-chested sheep. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Custom-built coil electrodes were placed around the left cardiac vagal branch. 3-10 days after surgery, conscious, direct recordings of cardiac vagal nerve activity (CVNA), cardiac output, coronary artery blood flow and heart rate were recorded in adult female sheep during whole-body treadmill exercise. Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), vasoactive intestinal peptide (VIP) ([4Cl−D-Phe6,Leu17]-VIP 25 μg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated. Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded CVNA increased during exercise. CVNA increases during the lowest exercise intensity and plateaus as exercise intensity increases. Left cardiac vagal branch, denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5 ± 5.9 ml/min, n = 8, cardiac vagal denervated: 32.7 ± 5.6 ml/min, n = 6, mean ± SEM. P = 2.5x10−7. Two-way ANOVA-interaction), cardiac output and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation (maximum exercise, paired: control: 68.2 ± 6.0 ml/min, VIP antagonism: 44.9 ± 3.9 ml/min, n = 6, mean ± SEM. P = 4.8x10−3. Two-way ANOVA-interaction). Our study challenges the conventional view and demonstrates that cardiac vagal nerve activity increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show that the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP and that acetylcholine has no role in modulating cardiac function during exercise. This work is supported by the Health Research Council of New Zealand 23/119 (Fellowship. JS) and the New Zealand Heart Foundation (JS, RR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice

Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca2+ levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT1B receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.

The state of microcirculation in patients with periodontal diseases and disorders of the occlusal relationships of the dentition

Background. The study of microcirculation disorders, as one of the key factors in the pathogenesis of periodontal diseases, is relevant in clinical dentistry. Premature contacts, acting as provoking factors for occlusal disorders, cause overload of individual teeth and aggravate the severity of inflammatory periodontal pathology. Objective registration of capillary blood flow and associated changes in the microvessels of the arteriolar and venular units in patients with periodontopathies and occlusal dis-orders will allow us to assess the degree and nature of tissue blood flow disorders in the gum tissue.Goal. Increasing the efficiency of diagnosing microcirculatory disorders in periodontal tissues in patients with chronic generalized mild periodontitis and disorders of the occlusal relationships of the dentition.Materials and methods. Using laser Doppler flowmetry (LDF), the state of mi-crocirculation in the periodontium was studied in 78 people aged 21–35 years with intact dentition and physiological occlusion, of which 33 people (group 1) had clinically healthy periodontium and the absence of occlusal disorders (group 1), with generalized chronic pulmonary periodontitis degree and premature occlusal contacts – 45 people (group 2). The microcirculation index (M), standard deviation (σ), and coefficient of variation (КV) were assessed. To obtain objective diagnostic data, amplitude-frequency analysis of the harmonic rhythms of LDF-grams was used with spectral decomposition into harmonic components of physiological oscillations of tissue blood flow (wavelet analysis).Results. In patients of group 2, in comparison with patients of group 1, a decrease in the level of periodontal blood perfusion, a reduction in the fluctuation of erythro-cyte flow and vasomotor activity of microvessels is determined, while a decrease in “active” and an increase in «passive» modulation of tissue blood flow contributes to an increase in the volume of circulating blood at arteriovenular anastomoses when the intensity of blood flow through the vessels of the capillary bed decreases.Conclusions. Patients of group 1 were diagnosed with a normoemic type of LDF-gram, which provides a relatively high degree of intensity of tissue blood flow, balance of regulatory mechanisms, and optimal trophism of periodontal tissues. In patients of group 2 with a spastic type of LDF-gram, characterized by a reduced level of perfusion, flux, vasomotor activity of microvessels, indicators of tissue blood flow and trophic function are significantly reduced.

Soft electrodes for simultaneous bio-potential and bio-impedance study of the face

The human body’s vascular system is a finely regulated network: blood vessels can change in shape (i.e. constrict, or dilate), their elastic response may shift and they may undergo temporary and partial blockages due to pressure applied by skeletal muscles in their immediate vicinity. Simultaneous measurement of muscle activation and the corresponding changes in vessel diameter, in particular at anatomical regions such as the face, is challenging, and how muscle activation constricts blood vessels has been experimentally largely overlooked. Here we report on a new electronic skin technology for facial investigations to address this challenge. The technology consists of screen-printed dry carbon electrodes on soft polyurethane substrate. Two dry electrode arrays were placed on the face: One array for bio-potential measurements to capture muscle activity and a second array for bio-impedance. For the bio-potential signals, independent component analysis (ICA) was used to differentiate different muscle activations. Four-contact bio-impedance measurements were used to extract changes (related to artery volume change), as well as beats per minute (BPM). We performed concurrent bio-potential and bio-impedance measurements in the face. From the simultaneous measurements we successfully captured fluctuations in the superficial temporal artery diameter in response to facial muscle activity, which ultimately changes blood flow. The observed changes in the face, following muscle activation, were consistent with measurements in the forearm and were found to be notably more intricate. Both at the arm and the face, a clear increase in the baseline impedance was recorded during muscle activation (artery narrowing), while the impedance changes signifying the pulse had a clear repetitive trend only at the forearm. These results reveal the direct connection between muscle activation and the blood vessels in their vicinity and start to unveil the complex mechanisms through which facial muscles might modulate blood flow and possibly affect human physiology.

Corpora cavernosa fibroblasts mediate penile erection.

Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.

Neurovascular coupling reflex from contralateral stimulation: System setup

Aims/Purpose: Neurovascular coupling (NVC) is the blood flow modulation in response to stimuli and has been extensively studied in the brain. Concerning the human retina, this behaviour has been only measured in the ipsilateral eye, where stimuli and observed effects involve the same eye. This work aims to set up the hardware to assess NVC in the contralateral eye and demonstrate its feasibility in edifying human retina‐retina or cortico‐retinal connections.Methods: Adaptive optics (AO) is a cutting‐edge technology in retinal fundus imaging, offering exceptional spatial resolution. The NVC effect was successfully assessed using the RTX1, an AO retinal camera capable of ipsilateral stimulation. The possible effects of contralateral stimulation can be readily assessed by providing RTX1 with an external flickering device. Furthermore, connecting the thread between previous fMRI results and photic stimulation in the ipsi‐ and contralateral retina can offer valuable information on uncharted interocular or brain‐retina neural pathways and lead to cost‐effective and non‐invasive biomarkers for neurodegenerative diseases or early brain vasculature impairment diagnosis.Results: Even though further optimization of flicker‐related parameters is necessary to investigate the contralateral NVC response, preliminary tests showed the successful integration of a fully operational contralateral stimulation prototype with the RTX1. The entire procedure has been documented, and all components have been thoroughly evaluated.Conclusions: These preliminary assessments precede a clinical study involving patients with type 1 Diabetes Mellitus and a control group of healthy individuals. It follows previous fMRI studies that showed impaired NVC in type 2 diabetic patients by measuring the BOLD (Blood Oxygen Level‐Dependent) response using block and event‐related optical stimuli. A comparative analysis of the findings aims to demonstrate the potential role of neurovascular uncoupling in the early pathogenesis of diabetic retinopathy.

Alleviation of Post-sepsis Ischaemia by Drag-Reducing Polymers.

Sepsis, leading to septic shock and multiple organ dysfunction syndrome, is characterised by inflammation, coagulopathy, and microvascular dysfunction, the primary cause of in-hospital mortality. Novel approaches are needed to prevent the consequences of sepsis. We showed that nanomolar concentrations of intravascular blood-soluble drag-reducing polymers (DRPs) significantly improve microvascular perfusion and tissue oxygenation and protect neurons in rat brains after traumatic brain injury and haemorrhagic shock. The aim of this work was to determine whether DRPs-enhanced perfusion could alleviate sepsis-associated microvascular dysregulation in a mouse model of lipopolysaccharide (LPS)-induced sepsis. LPS (Salmonella Thyphosa, 10mg/kg, i.v.) was administered intravenously to induce acute sepsis in C57BL/6 J mice. DRPs (final concentration 5ppm in the blood) or saline was injected i.v. (10 mice/group) 1h after LPS injection to evaluate the efficacy of haemorheological modulation of microvascular dysregulation. In-vivo two-photon laser scanning microscopy was used to monitor cerebral (parietal cortex) and peripheral (ear) microcirculation (i.v. fluorescein isothiocyanate dextran) and tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence) at a baseline and during 4h after septic shock induction. Differences between groups were determined using a two-way analysis of variance for multiple comparisons with post hoc testing. The statistical significance was set at p<0.05. LPS-induced sepsis led to microvascular dysfunction and tissue hypoxia in the brain and peripheral tissue (ear). DRPs alleviated microthrombosis formation, microvascular dysfunction, and tissue hypoxia in the brain and peripheral tissue compared to the saline control group (p<0.05). Therefore, haemorheological modulation of blood flow by DRPs effectively improves systemic and peripheral circulation, reducing microthrombosis formation, microvascular dysfunction, and tissue hypoxia that can alleviate sepsis, shock, and multiple organ dysfunction syndrome.

Modification of Peripheral Blood Flow and Angiogenesis by CO2 Water-Bath Therapy in Diabetic Skeletal Muscle with or without Ischemia.

Previously, it was shown that both blood flow and angiogenesis in the ischemic hind limb of diabetic rats were increased upon CO2 treatment for 4 weeks. In the present study, we have compared the effects of 6 weeks CO2 therapy in diabetic rats with or without peripheral ischemia. Diabetes was induced in rats by a tail vein injection of streptozotocin (65 mg/kg body weight), whereas peripheral ischemia was produced by occluding the femoral artery at 2 weeks of inducing diabetes. Both diabetic and diabetic-ischemic animals were treated with or without CO2 water-bath at 37 °C for 6 weeks (30 min/day; 5 days/week) starting at 2 weeks, after the induction of ischemia. CO2 treatment did not affect heart rate and R-R interval as well as plasma levels of creatine kinase, glucose, cholesterol, triglycerides and high density lipoproteins. Unlike the levels of plasma Ox-LDL, MDA and TNF-α, the levels of NO in diabetic group were increased by CO2 water-bath treatment. On the other hand, the levels of plasma Ox-LDL and MDA were decreased whereas that of NO was increased without any changes in TNF-α level in diabetic-ischemic animals upon CO2 therapy. Treatment of diabetic animals with CO2 increased peak, mean and minimal blood flow by 20, 49 and 43% whereas these values were increased by 53, 26 and 80% in the diabetic-ischemic group by CO2 therapy, respectively. Blood vessel count in diabetic and diabetic-ischemic skeletal muscles was increased by 73 and 136% by CO2 therapy, respectively. These data indicate that peripheral ischemia augmented the increase in blood flow and development of angiogenesis in diabetic skeletal muscle upon CO2 therapy. It is suggested that greater beneficial effects of CO2 therapy in diabetic-ischemic animals in comparison to diabetic group may be a consequence of difference of changes in the redox-sensitive signal transduction mechanisms.

Entropy-driven optimization of radiative Jeffrey tetrahybrid nanofluid flow through a stenosed bifurcated artery with Hall effects

Atherosclerosis, which causes the artery walls to thicken, the lumen to narrow, and the wall to thin in some places, is characterized by plaque accumulation in the arteries. These blood flow modifications can cause aneurysms and heart attacks if left unattended. Most of the arteries in the cardiovascular system are branched; therefore, a parent artery (main artery) with two daughter arteries (branched arteries) is considered in the present analysis. To examine the impact of various nanoparticle combinations on blood flow, four distinct nanoparticles, namely, gold (Au), graphene oxide (GO), copper (Cu), and tantalum (Ta), were injected into the blood to generate Au–GO–Cu–Ta/blood tetrahybrid nanofluid. In arteries with small diameters, blood behavior is regarded as non-Newtonian; therefore, blood behavior is governed by Jeffrey fluid in the present analysis. It has been investigated how Hall effects, Joule heating, radiation, and viscous dissipation affect blood flow through an artery that has an overlapping stenosis in the branches and a bell-shaped stenosis in the main artery. The approximation of mild stenosis is utilized to simplify and non-dimensionalize the governing equations. The Crank–Nicolson finite-difference scheme is used in MATLAB to solve the resulting equations. The results for velocity, temperature, wall shear stress, flow rate, and heat transfer rate are represented graphically. Furthermore, the entropy optimization has been performed for the specified problem. Enhancement in velocity with half of the bifurcation angle (η) can be observed from the velocity contours. The velocity of the tetrahybrid nanofluid increases with an increase in Jeffrey fluid parameter (λ1*) and shape parameter of the nanoparticles (n) as well. Introducing nanoparticles into the bloodstream can improve targeted drug delivery, allowing for more precise treatment at the cellular level. In addition, the tunable properties of nanoparticles offer possibilities for enhanced therapeutic and diagnostic treatments in a variety of medical disorders.