In vivo label-free measurement of blood flow velocity symmetry based on dual line scanning third-harmonic generation microscopy excited at the 1700 nm window

Measurement of bloodflow velocity is key to understanding physiology and pathology in vivo.While most measurements are performed at the middle of the blood vessel,little research has been done on characterizing the instantaneous bloodflow velocity distribution.This is mainly due to the lack of measurement technology with high spatial and temporal resolution.Here,we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation(THG)imaging technology.Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of bloodflow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo.Our results clearly show that the instantaneous bloodflow velocity is not symmetric under general conditions.

Modeling Blood Flow in Veins of Uniform Properties (Giraffe Jugular Vein)

This paper models the giraffe’s jugular veins as a uniform collapsible tube from a rigid skull. The equations governing one-dimensional steady flow through such a tube for various conditions have been developed. The effects of inertial and inclination angles that have not been discussed previously have been included. It has been shown that different flows for a uniform tube (vein) are possible. However, this flow matches that of a jugular vein which is supercritical, and the steady solution has been given by the balance between the driving forces of gravity and the viscous resistance to the flow at the right atrium of the heart must be sub-critical for a fixed right-atrium pressure which means that an elastic jump is required to return the flow to sub-critical from the supercritical flow upstream this type of relationship gives rise to flow limitation at the same time given any right atrium fixed pressure there exists a maximum flow rate which when exceeded the boundary conditions of the flow do not hold boundary conditions at the right atrium are not satisfied hence making the steady flow impossible this mechanism of flow limitation is slightly different from the other one in that causes airways through forced expiration from the observation made it is clearly shown that there is an intravascular pressure difference with a change in height.

Dynamic Non-Invasive Detection of NADH Based on Blood Flow-Mediated Skin Fluorescence (FMSF) Method

Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as a function of time in response to blocking and releasing of blood flow in a forearm are used as a measure of oxygen transport with blood to the tissue, which directly correlates with the skin microcirculation status. In this paper, a non-invasive dynamic monitoring system based on blood flow-mediated skin fluorescence (FMSF) technology is developed to monitor the NADH fluorescence intensity of skin tissue during the process of blocking reactive hyperemia. Simultaneously, laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) were used to observe blood flow, blood oxygen saturation (SOt2) and relative amount of hemoglobin (rHb) during the measurement process, which helped to explore NADH dynamics relevant physiological changes. A variety of parameters have been derived to describe NADH fluorescence curve based on the FMSF device. The experimental results are conducive to understanding the NADH measurement and the physiological processes related to it, which help FMSF to be a great avenue for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea level.The CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS groups.Statistical analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)curves.Results The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those without.Cortical CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery

BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric cancer.However,the immune status of postoperative patients is crucial for prognosis and survival,and immune cells play an important role in this process.Therefore,it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells,especially total T cells(CD3+),helper T cells(CD3+CD4+),and suppressor T cells(CD3+CD8+),and its relationship to sur-vival.AIM To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery,detect the levels of total T cells,helper T cells and suppressor T cells.METHODS A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study.Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells,helper T cells and inhibitory T cells.To explore the relationship between these immune markers and patient survival.RESULTS The results showed that the levels of total T cells,helper T cells,and suppressor T cells changed in patients after gastric cancer surgery.There was a significant positive correlation between total T cells,helper T cells and suppressor T cells(r=0.35,P<0.01;r=0.56,P<0.01).However,there was a negative correlation between helper T cells and suppressor T cells(r=-0.63,P<0.01).Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group(28.87±24.98 months vs 18.42±16.21 months).The survival curve shows that the curve of patients in the high-level group is shifted to the upper right,and that of the low-level group is shifted downward.There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time.CONCLUSION By detecting peripheral blood immune cells with flow cytometry,we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.

Thermogram-based estimation of foot arterial blood flow using neural networks

The altered blood flow in the foot is an important indicator of early diabetic foot complications.However,it is challenging to measure the blood flow at the whole foot scale.This study presents an approach for estimating the foot arterial blood flow using the temperature distribution and an artificial neural network.To quantify the relationship between the blood flow and the temperature distribution,a bioheat transfer model of a voxel-meshed foot tissue with discrete blood vessels is established based on the computed tomography(CT)sequential images and the anatomical information of the vascular structure.In our model,the heat transfer from blood vessels and tissue and the inter-domain heat exchange between them are considered thoroughly,and the computed temperatures are consistent with the experimental results.Analytical data are then used to train a neural network to determine the foot arterial blood flow.The trained network is able to estimate the objective blood flow for various degrees of stenosis in multiple blood vessels with an accuracy rate of more than 90%.Compared with the Pennes bioheat transfer equation,this model fully describes intra-and inter-domain heat transfer in blood vessels and tissue,closely approximating physiological conditions.By introducing a vascular component to an inverse model,the blood flow itself,rather than blood perfusion,can be estimated,directly informing vascular health.

Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain injury.However,the different effects and underlying mechanisms of these two model types have not been proven.This study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/s.We also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation occurred.In the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured area.Substantial motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment persisted.Transcriptome sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related genes.Morphological changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained enlarged.By analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the difference in the degree of damage among traumatic brain injury groups may reflect the mitochondrial changes.Taken together,differences in mitochondrial morphology and function between the 1 and 2 mm groups provide a new direction for the accurate classification of traumatic brain injury.Our results provide reliable data support and evaluation methods for promoting the establishment of standard mouse controlled cortical impingement model guidelines.

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Short-term effects of intravitreal triamcinolone acetonide injection on ocular blood flow evaluated with color Doppler ultrasonography

AIM:To evaluate the changes in ocular blood flow with color Doppler ultrasonography(CDU) after intravitreal triamcinolone acetonide(IVTA) injection.METHODS:A total of 46 patients who underwent IVTA(4 mg/0.1 mL) injection for diabetic macular edema(DME)(n =22), central retinal vein occlusion(CRVO)(n =12) and choroidal neovascular membrane(CNVM)(n =12) were included in the study. Peak systolic velocity(PSV), end diastolic velocity(EDV) and resistivity index(RI) were measured from the ophthalmic artery(OA), the central retinal artery(CRA) and the posterior ciliary artery(PCA)of each patient with CDU before, at the end of the first week and at the end of the first month following IVTA injection.RESULTS:In the DME group, PSV of OA at the first of the first month(mean ±SD)(37.48 ±10.87 cm/s) increased compared to pre-injection value(31.39 ±10.84 cm/s)(P =0.048). There was a statistically significant decrease(P =0.049) in PSV of CRA at the end of the first month(7.97±2.67 cm/s) compared to the pre-injection(9.47±3.37 cm/s).There was not any statistically significant difference onthe other parameters in the DME group. Also, there was not any statistically significant difference on the ocular blood flow values in the CRVO and CNVM groups.CONCLUSION:We observed that 4 mg/0.1 mL IVTA increased PSV of OA and decreased PSV of CRA in DME patients and did not have any effect on ocular blood flow values of CRVO and CNVM patients.

Assessment of Biological Reaction to Whole Body Vibration Training by Evaluating Changes in Salivary Components and Cutaneous Blood Flow

Aim: Whole body vibration (WBV) is thought to improve blood flow and autonomic balance and thereby induce a relaxation effect, which suggests its use for stress management. However, the relaxation effect of WBV training has not been objectively evaluated thus far. The purpose of this study was to determine the biological response to WBV training by measuring peripheral blood flow and salivary components using non-invasive techniques. Methods: Participants included 10 healthy volunteers (7 men, 3 women;mean age 33.8 ± 2.3) who provided oral consent and served as their own control. Each participant performed 15 types of stretching exercises for 10.5 min on the Power Plate? and cutaneous blood flow and salivary components were measured before and after the exercise. One week later, all participants performed the same exercise regimen for 10.5 min on a non-vibratory plate, and blood flow measurement and salivary tests were performed in a similar manner. Cutaneous blood flow was measured in the 4th digit for 1 min using the laser speckle flowgraphy. Saliva samples were evaluated for cortisol levels and α-amylase activity. To determine the effects of stretching exercises on the Power Plate? vs a non-vibratory plate, the differences in pre- and post-exercise peripheral blood flow, salivary cortisol levels, and salivary α-amylase activity were statistically evaluated by the t-test. Results: Mean blood flow before and after the exercise on the Power Plate? was 122.0 ± 54.2 and 156.7 ± 51.2, respectively;on a non-vibratory plate, blood flow was 136.6 ± 47.9 and 146.3 ± 38.3, respectively. The differences in pre-exercise and post-exercise values of the two training methods were not significant (p = 0.215). Mean cortisol levels before and after the exercise on the Power Plate? were 266.6 ± 125 and 204.9 ± 61.6, respectively;on a non-vibratory plate, the levels were 439.0 ± 121.7 and 425.8 ± 118.8, respectively. The differences in pre-exercise and post-exercise values of the two training methods were not significant (p = 0.384). Mean α-amylase activity before and after the exercise on the Power Plate? was 3.74 ± 2.89 and 5.40 ± 3.76, respectively;on a non-vibratory plate, the activity was 3.95 ± 2.23 and 3.28 ± 1.73. The differences in pre-exercise and post-exercise values of the two training methods were not significant (p = 0.115). Conclusion: Our results showed that a brief WBV training increased peripheral blood flow, reduced cortisol levels, and increased α-amylase activity. WBV appears to regulate autonomic activity, in particular, suppress sympathetic activity and improve bodily functions. Thus WBV exercise may be conductive for stress management, but further investigation is warranted to determine the optimal duration of WBV training for stress relief.

MEASUREMENT OF REGIONAL BONE BLOOD FLOW IN THE CANINE MANDIBULAR RAMUS USING RADIOLABELLED TOAD RED BLOOD CELLS

Toad red blood cells were used to measure regional bone blood flow in the canine mandibular ramus. The blood cells were labelled with sodium pertechnetate and fixed in 1 0%formalin; they were 22 × 15 μm in size and had a specific gravity close to that of dog red blood cells. These cells had no discernible effect on systemic hemodynamics after injection, did not agglutinate, were well mixed and evenly distributed throughout the body, and were completely extracted in one circulation through the mandible. The mandibular ramus was divided into six regions. and the blood flow rates in each were found to be similar to those reported in previous studies with radiolabelled carbonized, microspheres. Furthermore, the blood flow distribution pattern of the mandibular ramus determined in this study was identical to that of our previous study using the bone-seeking radionuclide method. We suggest that radiolabelled toad red blood cells are an ideal marker for measuring regional blood flow in the canine mandible.

Optimal velocity encoding during measurement of cerebral blood flow volume using phase-contrast magnetic resonance angiography

This study investigated the effect of velocity encoding on measurement of brain blood flow and blood volume of inflow and outflow using phase-contrast magnetic resonance angiography. A single two-dimensional phase-contrast magnetic resonance angiography slice was applied perpendicular to the internal carotid artery and the vertebral artery at C2 level. For each subject, the velocity encoding was set from 30 to 90 cm/s with an interval of 10 cm/s for a total of seven settings. Various velocity encodings greatly affected blood flow volume, maximal blood flow velocity and mean blood flow velocity in the internal carotid artery, but did not significantly affect vertebral arteries and jugular veins. When velocity encoding was 60-80 cm/s, the inflow blood volume was 655 _＋ 118 mL/min, and the outflow volume was 506 _＋ 186 mL/min. The ratio of outflow/inflow was steady at 0.78-0.83, and there was no aliasing in any of the images. These findings suggest that velocity encodings of 60 80 cm/s should be selected during measurement of cerebral blood flow volume using phase-contrast magnetic resonance angiography.

Pre-ligation of afflicted hepatic inflow and outflow blood vessels of lesioned liver lobe during hepatectomy

OBJECTIVE: To compare the merits of hepatectomy after pre-ligation of the hepatic inflow and outflow blood vessels of the lesioned liver lobe with those of Pringle's maneuver. METHODS: A total of 68 patients were divided into two groups A and B. In the group A (n=38), Pringle's maneuver was employed, whereas in the group B (n=30), hepatectomy after pre-ligation of the hepatic inflow and outflow blood vessels of the lesioned side of the liver was used. Perioperative blood loss, postoperative bleeding and drainage, time of liver function recovery as well as incidence of postoperative complications were compared between the 2 groups. RESULTS: The mean perioperative blood loss, the mean amount of postoperative bleeding and drainage, the time of liver function recovery as well as incidence of postoperative complications were significantly higher in the group A than in the group B (P<0.01). CONCLUSION: Hepatectomy after pre-ligation of the hepatic inflow and outflow blood vessels of the lesioned side of the liver is superior to Pringle's maneuver.

Approximate and Invariant Solutions of a Mathematical Model Describing a Simple One-Dimensional Blood Flow of Variable Density

We examine governing equations that could be used to model a one-dimensional blood flow within a pulsating elastic artery that is represented by a tube of varying cross-section. The model is considered from two perspectives. The first represents a singular perturbation theory providing explicit approximate solutions to the model, and the second is based on group theoretical modeling that provides exact solutions in implicit form. The main goal is to compare these two approaches and lay out the advantages and disadvantages of each approach.

Cerebral blood flow volume measurements of the carotid artery and ipsilateral branches using two-dimensional phase-contrast magnetic resonance angiography

The optimal velocity encoding of phase-contrast magnetic resonance angiography （PC MRA） in measuring cerebral blood flow volume （BFV） ranges from 60 to 80 cm/s. To verify the accuracy of two-dimensional （2D） PC MRA, the present study localized the region of interest at blood vessels of the neck using PC MRA based on three-dimensional time-of-flight sequences, and the velocity encoding was set to 80 cm/s. Results of the measurements showed that the error rate was 7.0±6.0% in the estimation of BFV in the internal carotid artery, the external carotid artery and the ipsilateral common carotid artery. There was no significant difference, and a significant correlation in BFV between internal carotid artery ＋ external carotid artery and ipsilateral common carotid artery. In addition, the BFV of the common carotid artery was correlated with that of the ipsilateral internal carotid artery. The main error was attributed to the external carotid artery and its branches. Therefore, after selecting the appropriate scanning parameters and protocols, 2D PC MRA is more accurate in the determination of BFV in the carotid arteries.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

RBC aggregation,deformation and adhesion to endothelium:Role of nitric oxide derived from L-Arginine and sodium nitroprusside

Red blood cells(RBCs)are the most abundant human blood cells.RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation.In turn,RBC properties depend on di®erent endogenous and exogenous factors.One such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory system.Since the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the samples.The RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne aggregometer.We confirmed that NO increases deformability and decreases aggregation of RBCs.We showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway involved.In the samples with the endothelium,the "bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by endothelium.Additionally,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under question.In our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not confirmed in another set of experiments.To our knowledge,this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.

Effects of Nitroglycerine on Erythrocyte Rheology:A Novel Mechanism to Explain the Enhancement of Nutrient Blood Flow to Ischemic Zones

Objectives Nitroglycerine (NTG) enhances coronary blood flow to compromised myocardium is important in relieving ischemia. However, the mechanism for this increase in myocardial blood flow (MBF) is not well defined. In small vessels and capillaries, relative blood viscosity plays a very important role in determining myocardial vascular resistance (MVR). MVR reduce is due partly to the increase in negative charge of erythrocyte surface. We therefore hypothesized that the enhancement of nutrient blood flow to zones of myocardial ischemia during NTG is partly secondary to reduced MVR and blood flow viscosity. The latter is affected by the negative charge of erythrocyte surface. Methods 6 dogs with LAD flow-limiting stenosis (group 1) and 6 dogs with LAD flow-limiting stenosis and LCx occmusion (group 2) were studied. At baseline and during intracoronary infusions of NTG (0.3-0.6 μg·kg-1·min-1), hemodynamics, MBF (mL·min-1·g-1), whole blood viscosity (WBη, mPa. S), elongation index (EI), eletrophoretic mobility of erythocytes (EME, [μ.s-1)/(V.cm-1)]) and percent wall thickening (%WT) were determined. MVR was calculated using driving pressure/MBF. Results As compared to baseline, no changes in hemodynamics were seen during NTG. MBF increased and MVR decreased significantly in normal bed, the central 25% and the entire of stenosed bed (P<0.05), with a decrease in WBη in both group 1 and group 2 dogs (18.6±9.7 % and 19.2±14.5 %, respectively). However, the % decrease in WBη was proportioned to the % increase in MBF or the % decrease in MVR only in the central 25% of stenosed bed (r=0.87, P<0.001), but not in the entire stenosed bed and normal bed. EI did not show statistically significant differences between during NTG and at baseline, but EME did increase. And the % decrease in WBη during NTG was related to the % increase in EME (r=0.83, P=0.01). Conclusions NTG reduced myocardial vascular resistance and blood viscosity due to the change of negative charge of erythrocyte surface may, in part, be the mechanism of the enhancement of nutrient blood flow to zones of myocardial ischemia. These results provide additional insights into the complex anti-ischemic effects of NTG.