Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021:A scientometric study

BACKGROUND The intestinal microcirculation functions in food absorption and metabolic substance exchanges.Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases.To date,there has not been a scientometric analysis of intestinal microcirculatory research.AIM To investigate the current status,development trends,and frontiers of intestinal microcirculatory research based on bibliometric analysis.METHODS VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database.The characteristics of each article,country of origin,institution,journal,cocitations,and other information were analyzed and visualized.RESULTS There were 1364 publications enrolled in the bibliometric analysis,exhibiting an upward trend from 2000 to 2021 with increased participation worldwide.The United States and Dalhousie University took the lead among countries and institutions,respectively.Shock was the most prolific journal,and Nature Reviews Microbiology Clinical had the most citations.The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels,diverse intestinal illnesses,and clinical treatment.CONCLUSION Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.

Advancements in Psoriasis Research: Skin Microcirculation and Its Prognostic Significance

Psoriasis, a chronic and recurring inflammatory skin disorder, is distinguished by the excessive proliferation of keratinocytes, immune cell infiltration, and angiogenesis. Ever since the observation of microvascular hyperplasia in psoriatic lesions, there has been a growing focus on exploring the intricate relationship between microcirculation and psoriasis. Furthermore, the potential utility of microcirculatory changes as prognostic indicators for psoriasis has garnered significant attention. This paper provides a comprehensive review of the role of skin microcirculation in psoriasis pathogenesis and its potential application as a clinical prognostic indicator.

Value of Tongue Color Combined with Sublingual Microcirculation in Predicting the Severity of Mild to Moderate Acute Cerebral Infarction

Objective:To explore the value of tongue color combined with sublingual microcirculation in predicting the severity of mild to moderate acute cerebral infarction(ACI).Methods:From January to December 2022,90 patients with ACI were admitted to the Department of Neurology of Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine.According to the NHISS score on the 5th day of admission,the patients were divided into mild group(35 cases)and moderate group(55 cases).The changes of tongue color and arterial lactate on the 5th day of admission were observed and monitored.Side-stream dark field imaging(SDF)was used to determine the total vascular density(TVD),perfused vascular density(PVD),perfused vascular ratio(PPV)and microvascular flow index(MFI).The multivariate logistic regression analysis was used to screen the risk factors for the severity of ACI,and the receiver operating characteristic curve(ROC)to evaluate their values in predicting ACI severity.Results:There was no significant difference in lactate between the two groups(P>0.05),and the frequency of red tongue in the mild group was higher,and the frequency of red tongue in the moderate group was significantly higher in the dark tongue group(P<0.05).The multivariate logistic regression analysis showed that PVD and PPV were independent risk factors for the severity of mild to moderate ACI(P<0.05).The ROC curve analysis showed that an area under the curve of 0.832 was achieved by the combination of PVD and PPV,which was larger than that of a single factor.Conclusion:Tongue color combined with sublingual microcirculation can be combined to predict the severity of mild to moderate ACI.

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions

BACKGROUND:Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis.DATA RESOURCES:PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)were searched from inception to August 1,2021.The search was limited to the English language only.Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis.Exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Fifty articles were included,and most of them were animal studies.These studies reported pathogenesis,including endothelial dysfunction,leukocyte recruitment and adhesion,microthrombus formation,microcirculation hypoperfusion,and redistribution of intestinal wall blood flow.The monitoring methods of intestinal microcirculation were also diverse,including handheld microscopes,intravital microscopy(IVM),laser Doppler blood flow instruments,laser speckle contrast imaging,tissue refl ectance spectrophotometry,biochemical markers of intestinal ischemia,and histopathological examination.In view of the related pathogenesis of intestinal microcirculation disorder in sepsis,existing studies also have diff erent opinions on its treatment.CONCLUSIONS:Limited by monitoring,there are few clinical studies on intestinal microcirculation dysfunction in sepsis.Related research mainly focuses on basic research,but some progress has also been made.Therefore,this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver.

Artificial intelligence based real-time microcirculation analysis system for laparoscopic colorectal surgery

BACKGROUND Colonic perfusion status can be assessed easily by indocyanine green(ICG)angiography to predict ischemia related anastomotic complications during laparoscopic colorectal surgery.Recently,various parameter-based perfusion analysis have been studied for quantitative evaluation,but the analysis results differ depending on the use of quantitative parameters due to differences in vascular anatomical structure.Therefore,it can help improve the accuracy and consistency by artificial intelligence(AI)based real-time analysis microperfusion(AIRAM).AIM To evaluate the feasibility of AIRAM to predict the risk of anastomotic complication in the patient with laparoscopic colorectal cancer surgery.METHODS The ICG curve was extracted from the region of interest(ROI)set in the ICG fluorescence video of the laparoscopic colorectal surgery.Pre-processing was performed to reduce AI performance degradation caused by external environment such as background,light source reflection,and camera shaking using MATLAB 2019 on an I7-8700k Intel central processing unit(CPU)PC.AI learning and evaluation were performed by dividing into a training patient group(n=50)and a test patient group(n=15).Training ICG curve data sets were classified and machine learned into 25 ICG curve patterns using a self-organizing map(SOM)network.The predictive reliability of anastomotic complications in a trained SOM network is verified using test set.RESULTS AI-based risk and the conventional quantitative parameters including T1/2max,time ratio(TR),and rising slope(RS)were consistent when colonic perfusion was favorable as steep increasing ICG curve pattern.When the ICG graph pattern showed stepped rise,the accuracy of conventional quantitative parameters decreased,but the AI-based classification maintained accuracy consistently.The receiver operating characteristic curves for conventional parameters and AI-based classification were comparable for predicting the anastomotic complication risks.Statistical performance verifications were improved in the AI-based analysis.AI analysis was evaluated as the most accurate parameter to predict the risk of anastomotic complications.The F1 score of the AI-based method increased by 31% for T1/2max,8% for TR,and 8% for RS.The processing time of AIRAM was measured as 48.03 s,which was suitable for real-time processing.CONCLUSION In conclusion,AI-based real-time microcirculation analysis had more accurate and consistent performance than the conventional parameter-based method.

Changes in nerve microcirculation following peripheral nerve compression

Following peripheral nerve compression, peripheral nerve microcirculation plays important roles in regulating the nerve microenvironment and neurotrophic substances, supplying blood and oxygen and maintaining neural conduction and axonal transport. This paper has retrospectively analyzed the articles published in the past 10 years that addressed the relationship between peripheral nerve compression and changes in intraneural microcirculation. In addition, we describe changes in different peripheral nerves, with the aim of providing help for further studies in peripheral nerve microcirculation and understanding its protective mechanism, and exploring new clinical methods for treating peripheral nerve compression from the perspective of neural microcirculation.

Expression of platelet endothelial cell adhesion molecule-1 between pancreatic microcirculation and peripheral circulation in rats with acute edematous pancreatitis

OBJECTIVE: To study the ehanges of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation anti pancreatic microcirculation in rats with acute edematous pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: PECAM-I expression on PMNs showed no significant difference between pancreatic microcirculation and peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated, but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1 expression had a significant difference between pancreatic microcirculation and peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1 expression on PMNs is in a converse way between pancreatic microcirculation and peripheral circulation in AEP.

In vivo observation of cerebral microcirculation after experimental subarachnoid hemorrhage in mice

Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.

Dynamic changes in cerebral microcirculation and hypoxia in the early stages of diffuse axonal injury

This study demonstrated that damage to the cerebral microvasculature, the formation of microthrombi and swelling of vascular endothelial cells occur early and peak 12 hours after injury in a rat model of diffuse axonal injury. Moreover, these pathological changes were most evident in the cerebral cortex. Cerebral microcirculatory dysfunction peaked later and had a shorter duration than axonal injury. In addition, the radioactive imaging agent, 99Tcm-4, 9-diaza-2, 3, 10, 10- tetramethyldodecan-2, 11 -dione dioxime, was used to visualize the dynamic changes that occur in tissue with cerebral hypoxia. The results demonstrated that cerebral hypoxia occurs at an early stage in diffuse axonal injury. Cerebral hypoxia was evident 12 hours after injury and declined slightly 24 hours after injury, but was significantly higher than in the control group. The pathological changes that underpin microcirculatory dysfunction did not occur at the same time as axonal injury, but did occur simultaneously with neuronal injury. Cerebral hypoxia plays a key role in promoting the secondary brain injury that occurs after diffuse axonal injury.

In vivo mice brain microcirculation monitoring based on contrast-enhanced SD-OCT

In this paper,we proposed a contrast-enhanced homemade spectral domain optical coherence tomography(SD-OCT)method for monitoring of brain microcirculation.We used the polyethylene glycol(PEG)-ylated gold nanorods(GNRs)as a contrast-enhanced agent,obtained clearly 2D and 3D OCT images of blood vessels and dynamic changes of probes in mouse blood vessels.Owing to high scattering of the PEG-GNRs,more tiny blood vessels can be imaged and the OCT signal can be enhanced by 5.87 dB after injection of PEG-GNRs for 20 min,the enhancement then declined gradually for 60 min.Our results demonstrate an effective technique for the enhanced imaging of blood vessels in vivo,especially for studies of the brain microcirculation,which could be serviced for disease mechanism research and therapeutic drug monitoring.

The effect of SphK1/S1P signaling pathway on hepatic sinus microcirculation in rats with hepatic ischemia-reperfusion injury

To the Editor:Hepatic ischemia-reperfusion(I/R)injury is the component of liver injury related to liver transplantation and liver surgery[1-3].The hepatic sinus microcirculation injury is a central part of hep-atic I/R injury,which eventually leads to hepatocyte injury.This process is closely associated with the participation of liver non-parenchymal cells such as Kuffer cells,hepatic stellate cells,liver sinusoidal endothelial cells(LSECs),and cytokines.

Studies on the flow and distribution of leukocytes in mesentery microcirculation of rats

AIM To study the effect of leukocyteendothelium interaction (LEI) on the flow anddistribution of leukocytes in microcirculationunder physiological condition.METHODS A microcirculation image multipleparameter computer analysis system (MIMPCAS)was used to study the flow and distribution ofleukocytes in mesentery microcirculation of ratsIn vivo.RESULTS The difference of visible leukocyteflux (VLF) was as high as 131 times in thearterioles and venules with similar diameter andblood velocity. The visible leukocytes rolledalong the blood vessel wall as a" jerky"movement. The frequency distribution of thevisible leukocyte velocity (VLV) showed a "twopeak" Curve. The low peak value was at 10 pm/ s-- 15 pm/ s while the high peak fell between25 pm/ s-- 30 pm/ s. With the increase of diameterof venules, VLF increased while the VLVremained at the same level. With the increase ofRBC velocity, VLV trends to elevate and VLF tofal I down.CONCLUSION The results herein might providea basic theory for the study on the mechanism ofLEI under physiological condition and novelmethods for the prevention and treatment of highLEI in many pathological

OBSERVATIONS ON THE CLINICAL EFFECT AND NAIL-FOLD MICROCIRCULATION IN THE TREATMENT OF 42 CASES OF CERVICAL SPONDYLOPATHY BY ACUPUNCTURE AND MASSAGE

Forty-two cases of cervical spondylopathy were divided into acupuncture andmassage groups. The therapeutic effects were observed comparatively, and the changes of nail-foldmicrocirculation of patients before and after treatment were observed at the same time. The resultsshowed that the effective rates of two groups were all 100%, no difference between them. The nailfold microcirculation of two groups was markedly ameliorated after treatment, and no significant dif-ference between them either.

The Effect of YiQiFuMai on Ischemic Heart Failure by Improve Myocardial Microcirculation and Increase eNOS and VEGF Expression

Objective: To assess the effects of traditional Chinese medicine YiQiFuMai on cardiac function during the progression of ischemic heart failure. Methods: Rabbits were divided into sham, heart failure, and YiQiFuMai groups. The ischemic heart failure model was established in New Zealand white rabbits, which were intraperitoneally injected with YiQiFuMai injection and 0.9% sodium chloride after the operation. After six weeks, cardiac function was examined by ultrasound;serum BNP levels were measured by ELISA;p-AKT, eNOS, ICAM-1 and VEGF levels were evaluated by real-time PCR and Western-Blot;pathological changes of the myocardial tissue were observed by H&E staining;CD31 expression in tissue samples was analyzed by immunohistochemistry. The ultrastructure and microcirculation of myocardial tissue specimens from the three groups were assessed by transmission electron microscopy. Results: YiQiFuMai decreased serum BNP levels, and increased LVEF and reduced LVEDD at 6 weeks postoperatively. In addition, YiQiFuMai can improve myocardial damage and microcirculation structure, as assessed by histology and transmission electron microscope. At the molecular level, treatment with YiQiFuMai resulted in increased eNOS, VEGF and p-AKT levels but reduced ICAM-1 amounts compared with the heart failure group. Conclusion: Ischemic heart failure damages the microvascular structure and functions of the myocardium. Treatment with YiQiFuMai potentially ameliorates microcirculatory damage and alleviates cardiac failure by improving endothelial function and angiogenesis, and inhibiting inflammatory cell adhesion.

Disorders of cerebrovascular angioarchitectonics and microcirculation in the etiology and pathogenesis of Alzheimer’s disease

There have recently appeared many reports dedicated to cerebral hemodynamics disorders in AD. However, certain specific aspects of cerebral blood flow and microcirculation during this disease are not fully understood. This research focuses on the identification of particular features of cerebral angioarchitectonics and microcirculation at preclinical and clinical AD stages and on the determination of their importance in AD etiology and pathogenesis. 164 patients participated in the research: Test Group—81 patients with different AD stages;Control Group— 83 patients with etiologically different neurodegenerative brain lesions with manifestations of dementia and cognitive impairment but without AD. All patients underwent: assessment of cognitive function (MMSE), severity of dementia (CDR) and AD stages (TDR), laboratory examination, computed tomography (CT), magnetic resonance imaging (MRI), brain scintigraphy (SG), rheoencephalography (REG) and cerebral multigated angiography (MUGA). All Test Group patients, irrespective of their AD stage, had abnormalities of the cerebral microcirculation manifested in dyscirculatory angiopathy of Alzheimer’s type (DAAT), namely: reduction of the capillary bed in the hippocampus and frontal-parietal regions;development of multiple arteriovenous shunts in the same regions;early venous dumping of arterial blood through these shunts with simultaneous filling of arteries and veins;development of abnormally enlarged lateral venous trunks that receive blood from the arterio-venous shunts;anomalous venous congestion at the border of frontal and parietal region;increased loop formation of distal intracranial arterial branches. Control group patients did not have combinations of such changes. These abnormalities are specific for AD and can affect amyloid beta metabolism contributing to its accumulation in the brain tissue and thereby stimulating AD progression.

Non-Invasive Assessment of Coronary Microcirculation in Heart Transplantation

Heart transplantation (HT) is an accepted treatment for end-stage heart failure (HF). Heart transplantation significantly increases survival, exercise capacity, quality of life and return to work in selected patients with advanced heart failure compared with conventional treatment. The survival rates have improved with the use of new immunosuppressive drugs, with a median survival after transplantation of approximately 11 years. The shortage of donor hearts represents a major limitation in this field. In addition many are the consequences of the limited effectiveness and complications of immunosuppressive therapy (i.e. antibody-mediated rejection, infection, hypertension, renal failure, malignancy and coronary artery vasculopathy). In particular, chronic rejection may occur months to years after the transplantation and is referred to as cardiac allograft vasculopathy (CAV). CAV occurs in 32% of the patients after 5 years and ensuing allograft failure from CAV eventually accounts for 30% of recipient deaths after transplantation. Cardiac allograft vasculopathy, involving coronary macro- and microcirculation, is caused by complicated interplay between immunologic and non-immunologic factors resulting in repetitive endothelial injury and localized sustained inflammatory response. Early diagnosis of microvascular dysfunction is substantial. In this review we analyze signs and symptoms of CAV presentation and the different methodologies to achieve an early and precise diagnosis. We will discuss invasive and non-invasive diagnostic tools and their specific role in evaluating graft’s function, morphology, the presence of coronary artery disease and possible microcirculation involvement.

Effects of Yibei multi-active elements on mesenteric microcirculation in rats

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