MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-16DOI: 10.1111/micc.12885
Hiroki Suzuki, Juri Murata, Miyuki Unekawa, Iwao Kanno, Yoshikane Izawa, Yutaka Tomita, Kenji F Tanaka, Jin Nakahara, Kazuto Masamoto
{"title":"Microfluctuations in Capillary Lumens Independent of Pericyte Lining Density in the Anesthetized Mouse Cortex.","authors":"Hiroki Suzuki, Juri Murata, Miyuki Unekawa, Iwao Kanno, Yoshikane Izawa, Yutaka Tomita, Kenji F Tanaka, Jin Nakahara, Kazuto Masamoto","doi":"10.1111/micc.12885","DOIUrl":"10.1111/micc.12885","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the spatiotemporal coherence of capillary lumen fluctuations in relation to spatial variations in the pericyte lining in the cortex of anesthetized mice.</p><p><strong>Methods: </strong>Two-photon microscopic angiography data (previously published) were reanalyzed, and spatial variations in capillary diameter fluctuations at rest and in capillary lining with vascular mural cells were measured along capillary centerlines.</p><p><strong>Results: </strong>Relatively large diameters of the capillaries (5.5 μm) coincided with a dense pericyte lining, while small capillaries (4.3 μm) had a sparse pericyte lining. Temporal variations had a frequency of about 0.1 Hz with an amplitude of 0.5 μm, which were negatively correlated with pericyte lining density. Spatial frequency analysis further revealed a common pattern of spatial variations in capillary diameter and pericyte lining, but temporal variations differed. The temporal variations in capillary lumens were locally distinct from those in neighboring locations, suggesting intrinsic fluctuations independent of the pericyte lining.</p><p><strong>Conclusions: </strong>Capillary lumens in the brain exhibit slow microfluctuations that are independent of pericyte lining. These microfluctuations could affect the distribution of flowing blood cells and may be important for homogenizing their distribution in capillary networks.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-26DOI: 10.1111/micc.12890
Fabian Müller-Graf, Dominik Wrede, Lena Bork, Gerd Klinkmann, Moritz Flick, Daniel A Reuter, Amelie R Zitzmann, Stephan H Böhm, Susanne Reuter
{"title":"Quantification of Video Sequences of the Microcirculation: A Comparison Between Automated Analysis Using Analysis Manager and Manual Analysis Using Capillary Mapper.","authors":"Fabian Müller-Graf, Dominik Wrede, Lena Bork, Gerd Klinkmann, Moritz Flick, Daniel A Reuter, Amelie R Zitzmann, Stephan H Böhm, Susanne Reuter","doi":"10.1111/micc.12890","DOIUrl":"10.1111/micc.12890","url":null,"abstract":"<p><strong>Objective: </strong>Microcirculatory disturbances can contribute to organ dysfunction in patients undergoing major surgeries and critical illness. Incident dark field imaging (CytoCam, Braedius Medical BV, Huizen, Netherlands) provides direct visualization of the microcirculation. To utilize this method in daily clinical practice, automated image analysis is essential. This study aims to compare the automated analysis of recorded microcirculation video sequences using CytoCamTools V2 Analysis Manager (Braedius Medical BV) with established manual analysis using Capillary Mapper (Version 1.4.5, University Hospital Münster, Germany) as reference method.</p><p><strong>Methods: </strong>Sublingual microcirculation video sequences were recorded in patients undergoing laparotomy at four time points (before surgery, 2 and 6 h after surgery, and on the first postoperative day) using incident dark field imaging. Agreement between automated and manual analysis of total vessel density (TVD), perfused vessel density (PVD), and proportion of perfused vessels (PPV) was compared using intraclass correlation (ICC) and Bland-Altman method.</p><p><strong>Results: </strong>A total of 336 videos from 30 patients were analyzed. The ICC between the two measurement methods was 0.13 for TVD, 0.14 for PVD, and 0.16 for PPV. Bland-Altman analysis showed mean differences (95% limits of agreement) of 10.46 mm/mm<sup>2</sup> (-1.73-22.65 mm/mm<sup>2</sup>) for TVD, 8.25 mm/mm<sup>2</sup> (-9.88-26.39 mm/mm<sup>2</sup>) for PVD, and - 3.96% (-59.58%-51.65%) for PPV.</p><p><strong>Discussion: </strong>Automated microcirculatory analysis using the Analysis Manager did not show clinically acceptable agreement with manual analysis using Capillary Mapper. Consequently, automated video analysis using the Analysis Manager does not appear to be a suitable approach.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: DRKS00020264.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-25DOI: 10.1111/micc.12886
Rahul Ramanathan, Andy Borum, David M Rooney, Sina Y Rabbany
{"title":"Modeling Hemodynamics in Three-Dimensional, Biomimetic, Branched, Microfluidic, Vascular Networks.","authors":"Rahul Ramanathan, Andy Borum, David M Rooney, Sina Y Rabbany","doi":"10.1111/micc.12886","DOIUrl":"10.1111/micc.12886","url":null,"abstract":"<p><strong>Objective: </strong>Neovascularization has been extensively studied because of its significant role in both physiological processes and diseases. The significance of vascular microfluidic platforms lies in its essential role in recreating an in vitro environment capable of supporting cellular and tissue systems through the process of neovascularization. Biomechanical properties in a tissue engineered system use fluid flow and transport properties to recapitulate physiological systems. This enables mimicry of organ systems which can further personalized and regenerative medicine. Thus, fluid hemodynamics can be used to study these flow patterns and create a system that mimics real physiological pathways and processes. The establishment of stable flow pathways encourages endothelial cells (ECs) ECs to undergo neovascularization. Specifically, the shear stress applied in capillary beds generates the increased proliferation and differentiation of ECs to build larger microcirculatory beds.</p><p><strong>Mathematical framework: </strong>Here, we describe a mathematical model that uses branching patterns and vessel morphology to predict hemodynamic parameters in capillary beds.</p><p><strong>Results: </strong>A retinal capillary bed is used as one-use case of our model to show how the mathematical framework can be used to determine hemodynamic parameters for any microfluidic system.</p><p><strong>Conclusion: </strong>In doing so, this tool can be altered to be used to supplement emerging research areas in neovascularization.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-28DOI: 10.1111/micc.12884
Karin Wårdell, Johan Richter, Peter Zsigmond
{"title":"Cerebral Microcirculation: Progress and Outlook of Laser Doppler Flowmetry in Neurosurgery and Neurointensive Care.","authors":"Karin Wårdell, Johan Richter, Peter Zsigmond","doi":"10.1111/micc.12884","DOIUrl":"10.1111/micc.12884","url":null,"abstract":"<p><p>Laser Doppler flowmetry (LDF) is a well-established technique for the investigation of tissue microcirculation. Compared to skin, the use in the human brain is sparse. The measurement of cerebral microcirculation in neurointensive care and during neurosurgery is challenging and requires adaptation to the respective clinical setting. The aim of the review is to present state of the art and progress in neurosurgery and neurointensive care where LDF has proven useful and can find clinical importance in the investigation of cerebral microcirculation. The literature in the field is summarized and recent technical improvements regarding LDF systems and fiber optical probe designs for neurosurgical and neurocritical care described. By combining two signals from the LDF unit, the measurement of the microcirculation (Perfusion) and gray whiteness (TLI) of the brain tissue, the full potential of the device is achieved. For example, a forward-looking LDF-probe detects high-risk hemorrhage areas and gray-white matter boundaries along intraoperative trajectories during stereotactic neurosurgery. Proof of principles are given for LDF as a guidance tool in deep brain stimulation implantation, brain tumor needle biopsies, and as long-term monitoring device in neurocritical care. With well-designed fiber optical probes, surgical fixation, and signal processing for movement reduction, LDF monitoring of the cerebral microcirculation is successful up to 10 days. The use of LDF can be combined with other physiological measurement techniques, for example, fluorescence spectroscopy for identification of glioblastoma during tumor surgery. Fiber optics can also be used during magnetic resonance imaging (MRI). Despite the many advantages, fiber optical LDF has not yet reached its full potential in clinical neuro-applications. Multicenter studies are required to further evaluate LDF in neurosurgery and neurointensive care. In conclusion, the present status of LDF in neurosurgery and neurointensive care has been reviewed. By combining Perfusion and TLI with tailored probe designs the full potential of LDF can be achived in measuring cerebral microcirculation. This includes guidance during DBS implantation and needle biopsies, and long-term monitoring in neurocritical care.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-27DOI: 10.1111/micc.12887
Guillermo Arroyo-Ataz, Dennis Jones
{"title":"Overview of Lymphatic Muscle Cells in Development, Physiology, and Disease.","authors":"Guillermo Arroyo-Ataz, Dennis Jones","doi":"10.1111/micc.12887","DOIUrl":"10.1111/micc.12887","url":null,"abstract":"<p><p>Lymphatic muscle cells (LMCs) are indispensable for proper functioning of the lymphatic system, as they provide the driving force for lymph transport. Recent studies have advanced our understanding of the molecular mechanisms that regulate LMCs, which control rhythmic contraction and vessel tone of lymphatic vessels-traits also found in cardiac and vascular smooth muscle. In this review, we discuss the molecular pathways that orchestrate LMC-mediated contractility and summarize current knowledge about their developmental origin, which may shed light on the distinct contractile characteristics of LMCs. Further, we highlight the growing evidence implicating LMC dysregulation in the pathogenesis of lymphedema and other diseases related to lymphatic vessel dysfunction. Given the limited number and efficacy of existing therapies to treat lymphedema, LMCs present a promising focus for identifying novel therapeutic targets aimed at improving lymphatic vessel contractility. Here, we discuss LMCs in health and disease, as well as therapeutic strategies aimed at targeting them to improve lymphatic vessel function.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-09-26DOI: 10.1111/micc.12888
Katie Anne Fopiano, Saltanat Zhazykbayeva, Ibrahim El-Battrawy, Vadym Buncha, William M Pearson, Davis J Hardell, Liwei Lang, Nazha Hamdani, Zsolt Bagi
{"title":"PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF.","authors":"Katie Anne Fopiano, Saltanat Zhazykbayeva, Ibrahim El-Battrawy, Vadym Buncha, William M Pearson, Davis J Hardell, Liwei Lang, Nazha Hamdani, Zsolt Bagi","doi":"10.1111/micc.12888","DOIUrl":"10.1111/micc.12888","url":null,"abstract":"<p><strong>Objective: </strong>Heart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF.</p><p><strong>Methods and results: </strong>The obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3-nitrotyrosine. Liquid chromatography-mass spectrometry (LC-MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment.</p><p><strong>Conclusions: </strong>Thus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX-dependent antioxidant mechanisms.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Beraprost on Intestinal Microcirculation and Barrier Function in a Mouse Model of Renal Failure.","authors":"Akira Hirano, Hiroyuki Kadoya, Masanobu Takasu, Tsukasa Iwakura, Eriko Kajimoto, Rie Tatsugawa, Takumi Matsuura, Hajimu Kurumatani, Toshiya Yamamoto, Kengo Kidokoro, Seiji Kishi, Hajime Nagasu, Tamaki Sasaki, Naoki Kashihara","doi":"10.1111/micc.12889","DOIUrl":"10.1111/micc.12889","url":null,"abstract":"<p><strong>Objective: </strong>Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI<sub>2</sub>), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI<sub>2</sub> improves intestinal microcirculation and barrier function via endothelial protective effects.</p><p><strong>Methods: </strong>ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI<sub>2</sub> effects. Beraprost served as PGI<sub>2</sub>. PGI<sub>2</sub> administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions.</p><p><strong>Results: </strong>We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2-fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration.</p><p><strong>Conclusions: </strong>Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrocirculationPub Date : 2024-11-01Epub Date: 2024-10-10DOI: 10.1111/micc.12891
Carolien Volleman, S Jorinde Raasveld, Faridi S Jamaludin, Alexander P J Vlaar, Charissa E van den Brom
{"title":"Microcirculatory Perfusion Disturbances During Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review.","authors":"Carolien Volleman, S Jorinde Raasveld, Faridi S Jamaludin, Alexander P J Vlaar, Charissa E van den Brom","doi":"10.1111/micc.12891","DOIUrl":"10.1111/micc.12891","url":null,"abstract":"<p><p>Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes","authors":"Kareem El-Ghazawi, Ukpong B. Eyo, Shayn M. Peirce","doi":"10.1111/micc.12877","DOIUrl":"10.1111/micc.12877","url":null,"abstract":"<p>The brain microvasculature, which delivers oxygen and nutrients and forms a critical barrier protecting the central nervous system via capillaries, is deleteriously affected by both Alzheimer's disease (AD) and type 2 diabetes (T2D). T2D patients have an increased risk of developing AD, suggesting potentially related microvascular pathological mechanisms. Pericytes are an ideal cell type to study for functional links between AD and T2D. These specialized capillary-enwrapping cells regulate capillary density, lumen diameter, and blood flow. Pericytes also maintain endothelial tight junctions to ensure blood–brain barrier integrity, modulation of immune cell extravasation, and clearance of toxins. Changes in these phenomena have been observed in both AD and T2D, implicating “pericyte pathology” as a common feature of AD and T2D. This review examines the mechanisms of AD and T2D from the perspective of the brain microvasculature, highlighting how pericyte pathology contributes to both diseases. Our review identifies voids in understanding how AD and T2D negatively impact the brain microvasculature and suggests future studies to examine the intersections of these diseases.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12877","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Z. Jamal, Blake W. Dieckmann, Gary W. McCollum, John S. Penn, Ashwath Jayagopal, MD Imam Uddin
{"title":"Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion","authors":"Sara Z. Jamal, Blake W. Dieckmann, Gary W. McCollum, John S. Penn, Ashwath Jayagopal, MD Imam Uddin","doi":"10.1111/micc.12883","DOIUrl":"10.1111/micc.12883","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser-induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A reliable and reproducible model of laser-induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX-4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age-matched control retinas were analyzed using qRT-PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL-positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT-PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia-related neuronal cell damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Perspectives</h3>\u0000 \u0000 <p>Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12883","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}