Capillary Network Research Articles

Pathomorphological characteristics of heat stress in the experiment.

The purpose of this research was to explore some morphological, physiological, and biochemical changes in female and fetal Wistar rats under heat stress. The experiment involved 30 animals, including two experimental groups (pregnant and nonpregnant females) kept under heat stress at 32°C and one control group consisting of healthy individuals kept in standard vivarium conditions. After dissection, fixation, dehydration, and primary processing, tissue samples were embedded in a mixture of paraffin and lanolin to obtain material for sections. Sections were made using a freezing and angular microtome and stained with hematoxylin and fuchsine solutions. Changes in morphology were assessed by microscopy using a Leitz DIAPLAN system. As a result of heat stress, an increase in linear cell size, capillary network area, and adrenal mass was observed; adipocytes lost lipid vacuoles; prismatic thyroid cells were replaced by flat cells; hypothyroidism; an increase in the number of osteocyte lacunae; and increased osteoclast activity in bone tissue; interstitial and intracellular oedema and caryopycnosis of ventricular cardiomyocytes; reduction in the diameter of skeletal muscle fibers and replacement of tissue with collagen fibers; water loss in the structure of myofibrils; destructive local changes, hyperchromatosis and caryopycnosis of the hippocampus. The data obtained allows predicting the possible consequences of prolonged overheating of tissues of other vertebrates and the human body.

Enhancing Building Energy Efficiency: Leaf Transpiration Inspired Construction of Lignin-Based Wood Plastic Composites for Building Energy Conservation

Incorporating phase change materials (PCMs) into buildings represents a strategic method for reducing reliance on air conditioning systems and decreasing energy usage consequently. Inspired by leaf veins providing channels for transpiration, lignin porous carbon (LPC) was synthesized by chemical activation, showing a vein pore structure. The capillary network system of the LPC provided more channel to adsorb PCM through surface tension and capillary force, achieving an impressive loading capacity of LPC for polyethylene glycol (PEG) (75%), which demonstrated exceptional heat storage capability (133.21 J/g). The lignin-derived wood-plastic composite (L-WPC) was further prepared. With the gradual increase of LPC/PEG, the latent heat of L-WPC increased gradually. The ΔHm, ΔHc and energy storage efficiency of L-WPC-50 (incorporated 50 wt% LPC/PEG-75) reached 39.99 J/g, 42.65 J/g and 90.26%, respectively. The vein pore structure of LPC also provided a thermal conductivity link for L-WPC. L-WPC-50 demonstrated an increased thermal conductivity (0.66 W/(m·K)) and a reduced thermal diffusion coefficient (0.24 mm2/s), optimizing the effectiveness of the phase transition. Additionally, L-WPC-50 displayed satisfactory mechanical properties and dimensional stability, with tensile strength, bending modulus and water absorption thickness swelling rate measuring 14.40 MPa, 1043.72 MPa, and 1.61% respectively. It introduced a feasible approach for utilizing biomass in enhancing building energy efficiency, marking a significant stride towards reducing building energy consumption and advocating sustainable energy practices.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Computational Insights into the Interplay of Mechanical Forces in Angiogenesis.

This study employs a meshless computational model to investigate the impacts of compression and traction on angiogenesis, exploring their effects on vascular endothelial growth factor (VEGF) diffusion and subsequent capillary network formation. Three distinct initial domain geometries were defined to simulate variations in endothelial cell sprouting and VEGF release. Compression and traction were applied, and the ensuing effects on VEGF diffusion coefficients were analysed. Compression promoted angiogenesis, increasing capillary network density. The reduction in the VEGF diffusion coefficient under compression altered VEGF concentration, impacting endothelial cell migration patterns. The findings were consistent across diverse simulation scenarios, demonstrating the robust influence of compression on angiogenesis. This computational study enhances our understanding of the intricate interplay between mechanical forces and angiogenesis. Compression emerges as an effective mediator of angiogenesis, influencing VEGF diffusion and vascular pattern. These insights may contribute to innovative therapeutic strategies for angiogenesis-related disorders, fostering tissue regeneration and addressing diseases where angiogenesis is crucial.

Optimizing Last-Mile Delivery: A Multi-Criteria Approach with Automated Smart Lockers, Capillary Distribution and Crowdshipping

Background: This publication presents a review, multiple criteria optimization models, and a practical example pertaining to the integration of automated smart locker systems, capillary distribution networks, crowdshipping, last-mile delivery and supply chain management. This publication addresses challenges in logistics and transportation, aiming to enhance efficiency, reduce costs and improve customer satisfaction. This study integrates automated smart locker systems, capillary distribution networks, crowdshipping, last-mile delivery and supply chain management. Methods: A review of the existing literature synthesizes key concepts, such as facility location problems, vehicle routing problems and the mathematical programming approach, to optimize supply chain operations. Conceptual optimization models are formulated to solve the complex decision-making process involved in last-mile delivery, considering multiple objectives, including cost minimization, delivery time optimization, service level minimization, capacity optimization, vehicle minimization and resource utilization. Results: The multiple criteria approaches combine the vehicle routing problem and facility location problem, demonstrating the practical applicability of the proposed methodology in a real-world case study within a logistics company. Conclusions: The execution of multi-criteria models optimizes automated smart locker deployment, capillary distribution design, crowdshipping and last-mile delivery strategies, showcasing its effectiveness in the logistics sector.

Angiogenic potential in periodontal stem cells from upper and lower jaw: A pilot study.

Teeth and supporting oral tissues are attractive and accessible sources of stem cells. Periodontal ligament stem cells (PDLSC) are readily isolated from extracted third molars, and exhibit the ability to self-renew and differentiate into multiple mesodermal cell fates. Clinical experience suggests that the exact location of periodontal defects affects the oral bone remodeling and wound healing. Compared to the mandible, the maxilla heals quicker and more efficiently. Angiogenesis is key in tissue regeneration including dental tissues, yet few studies focus on the angiogenic potential of PDLSC, none of which considered the differences between upper and lower jaw PDLSC (u-PDLSC and l-PDLSC, respectively). Here we studied the angiogenic potential of u-PDLSC and l-PDLSC and compared the results to well-established mesenchymal stem cells (MSC). Cells were characterized in terms of surface markers, proliferation, and vascular endothelial growth factor (VEGF) secretion, and angiogenic assays were performed. Newly formed capillaries were stained with CD31, and their expression of platelet endothelial cell adhesion molecule (PECAM-1), angiopoietin 2 (ANGPT2), and vascular endothelial growth factor receptor 1 and 2 (VEGFR-1, VEGFR-2) were measured. Periodontal stem cells from the upper jaw showed a higher proliferation capacity, secreted more VEGF, and formed capillary networks faster and denser than l-PDLSC. Gene expression of angiogenesis-related genes was significantly higher in u-PDLSC than in l-PDLSC or MSC, given that culture conditions were suitable. The oral cavity is a valuable source of stem cells, particularly PDLSC, which are promising for oral tissue engineering due to their robust growth, lifelong accessibility, low immunogenicity, and strong differentiation potential. Notably, u-PDLSC exhibit higher VEGF secretion and accelerate capillary formation compared to l-PDLSC or MSC. This study suggests a potential molecular mechanism in capillary formation, emphasizing the significance of precise location isolation of PDLSC.

Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice.

It is not well-understood how type 1 diabetes (T1DM) affects skeletal muscle histological phenotype, particularly capillarisation. This study aimed to analyze skeletal muscle myosin heavy chain (MyHC) fibre type changes and 3D capillary network characteristics in experimental T1DM mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n =12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles were characterized based on the expression of MyHC isoforms, while capillaries of the gluteus maximus were assessed with immunofluorescence staining, confocal laser microscopy and 3D image analysis. STZ-induced diabetic mice exhibited elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly expressed fast-twitch type 2b fibers, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibers and comparable type 1 fiber densities (26.2 ± 14.6% vs 21.9 ± 13.5%) relative to diabetic mice. T1DM mice showed reduced fiber diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus of diabetic mice compared to controls (P < 0.05). Overall, T1DM induced significant changes in the skeletal muscle, including shifts in MyHC fibre types, decreased fibre diameters, and increased relative capillarisation, possibly due to muscle fibre atrophy. Our findings emphasize the superior detail provided by the 3D analytical method for characterizing skeletal muscle capillary architecture, highlighting caution in interpreting 2D data for capillary changes in T1DM.

Calcium-activated chloride channels in pericytes shape capillary electrical signaling

The brain vasculature, composed of penetrating arterioles (PAs) giving rise to the dense capillary network, facilitates continuous energy substrate delivery to neurons and glia by tightly controlling blood flow. The capillaries are covered by perivascular cells known as pericytes, which exhibit varying morphological and physiological properties based on their location in relation to the terminal arteriole, and these contribute to blood flow control within the capillary network in distinct ways. Thin-strand pericytes —the focus of this study—are located in the deep capillary bed. Serendipitously, we have discovered a robust chloride current during perforated patch clamp experiments on these thin-strand pericytes. We hypothesized that this current is mediated by calcium-activated chloride channels (CaCCs), which may influence electrical signaling and thereby regulate blood flow. Our data reveal that this robust current is dependent on external calcium concentration and can be blocked by voltage-gated calcium channel blockers, depletion of endoplasmic reticulum calcium stores, and calcium-activated chloride channel blockers. This suggests a mechanism wherein calcium entry into the cytosol via voltage-gated channels and intracellular calcium release govern the activity of CaCCs in the thin-strand pericyte membrane. Using two-photon microscopy, we further observed that blocking CaCCs led to PA dilation and hyperemia. Together, our data indicate a novel role for CaCCs in thin-strand pericytes, where they modulate electrical signaling across the capillary bed in response to intracellular calcium activity. By providing a depolarizing signal countering hyperpolarizing electrical signaling, these channels contribute to the intricate regulation of blood flow and vessel dilation. This work was supported by the NIH (grants 1R01AG066645, 5R01NS115401, 1DP2NS121347-01), and the American Heart Association (19IPLOI34660108). 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.

Machine learning techniques for predicting microvascular network hemodynamics

Existing techniques to image microvascular networks in vivo do not allow a direct and accurate measurement of several hemodynamic variables such as the wall shear stress (WSS). They cannot also provide a full 3D characterization of blood velocity and red blood cell (RBC) concentration profiles in every vessel in a microvascular network. Such physiological parameters however play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical models of network blood flow, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D blood velocity, RBC concentration and WSS profiles as these models assume one-dimensional flow governed by Poiseuille’s law. In contrast, high-fidelity computational models that simulate flow of blood as a suspension of deformable RBCs and model the 3D vessel geometry can readily predict such physiological variables with high accuracy. Such high-fidelity computational models have recently been applied to predict hemodynamic variables in microvascular networks in silico composed of many vessels and vascular junctions. Such models, however, tend to become computationally expensive with increasing size of the network; therefore, they are not feasible for use in large networks at organ scale. To overcome this limitation, we developed a machine learning (ML) approach that can predict hemodynamic variables in 3D and with high accuracy. The ML models are based on artificial neural network and convolution-based U-net models. Using experimentally acquired images of the microvascular networks, inputs at a few inlets, and a “bank” of database that we have developed, these ML models can predict flow and RBC distribution in all vessels in the network, 3D blood velocity and RBC concentration profiles over the cross-section of every vessel, 3D WSS profiles, and time-dependent variations in blood flow in any vessel. The prediction from the ML models compare very well against the true data. Also, the prediction time using ML is significantly less than that of the high-fidelity models. The current ML models, which to our knowledge are the first of their kind, are highly promising for image-based predictions of sub-cellular resolved capillary hemodynamics in organ-scale networks. This study paves the way for AI to make hemodynamic predictions in organ-scale capillary vessel networks while retaining the sub-cellular scale details and overcoming the limitations of the in vivo imaging techniques, with potential applications in hematological and microvascular disorders, angiogenesis, and vascular-mediated drug delivery. Funded by NIH (R01-EY033003) and NSF (CBET 2302212). 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.

Store-operated calcium entry is necessary for sustained K+-induced capillary-to-arteriole dilation in the brain

Neurovascular coupling (NVC) is a physiological process that directs blood flow to the most active regions of the brain. The extensive network of capillaries in the brain acts as a sensory web that detects local neuronal activity and orchestrates the dilation of upstream arterioles to meet the brain’s metabolic demands. Activation of inwardly rectifying K+ (KIR) channels on brain capillary endothelial cells (cECs) by modest concentrations of extracellular K+ initiates retrograde propagating hyperpolarizing signals that induce vasodilation and increase blood flow. Brain capillaries exhibit diverse and dynamic patterns of Ca2+ signaling in vivo, but little is known about their origins or physiological function. Store-operated Ca2+ entry (SOCE) is fundamental to Ca2+homeostasis in non-excitable cells, but the contribution of SOCE to capillary-to-arteriole dilation has not been explored. Here, we report that brain cECs express the endoplasmic reticulum-resident Ca2+ sensing protein stromal interaction molecule 1 ( Stim1) and the Ca2+-selective Orai1 and Orai3 channels. Ca2+ imaging experiments using brain cECs from transgenic mice expressing GCaMP8 in the endothelium or loaded with Fluo-4 showed that these cells exhibited robust SOCE that was blocked by the Orai1 inhibitor Synta66. Using EC-specific knockout (ecKO) mice, we found that Stim1 and Orai1 but not Orai3 are required for SOCE. Ex vivo brain microvascular preparations consisting of cannulated and pressured parenchymal arterioles with intact capillary beds were used to examine the role of SOCE in capillary-to-arteriole dilation. Arteriole dilation in response to a train of K+ pulses applied to capillaries exhibited dramatic run-down when preparations were treated with Snyta66 or when tissues from Stim1-ecKO mice were used. Preparations from Orai3-ecKO mice did not demonstrate run-down. Moreover, inhibition of Ca2+-activated K+ (SK and IK) channels also induced run-down, suggesting that SOCE activates SK and IK channels to boost KIR-induced hyperpolarizing signals to dilate upstream arterioles during multiple stimulations. We conclude that brain cECs exhibit SOCE that requires Stim1 and Orai1. Our data further show that brain cEC SOCE is necessary for capillary-to-arteriole dilation during repeated stimulations, suggesting an essential role for SOCE in NVC. R35HL155008, R33NS115132, and P20GM130459 (to SE). 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.

Oriented Interpenetrating Capillary Network with Surface Engineering by Porous ZnO from Wood for Membrane Emulsification.

Membrane emulsification technology has garnered increasing interest in emulsion preparation due to controllable droplet size, narrower droplet size distribution, low energy consumption, simple process design and excellent reproducibility. Nevertheless, the pore structure and surface engineering in membrane materials design play a crucial role in achieving high-quality emulsions with high throughput simultaneously. In this work, an oriented interpenetrating capillary network composed of highly aligned and interconnected wood cell lumens has been utilized to fabricate an emulsion membrane. A novel honeycomb porous ZnO layer obtained by a seed prefabrication-hydrothermal growth method was designed to reconstruct wood channel surfaces for enhanced microfluid mixing. The results show that through the unique capillary mesh microstructure of wood, the emulsion droplets were smaller in size, had narrower pore-size distribution, and were easy to obtain under high throughput conditions. Meanwhile, a well-designed ZnO layer could further improve the emulsion quality of a wood membrane, while the emulsifying throughput is still maintained at a higher level. This demonstrates that the convection process of the microfluid in these wood capillary channels was intensified markedly. This study not only develops advanced membrane materials in emulsion preparation, but also introduces a brand-new field for functional applications of wood.

Diagnosis of Skin Burn-Induced Colon Circulatory Disorders Using Optical Coherence Tomography Angiography and Laser Doppler Flowmetry (Experimental Study).

A deep thermal skin burn was induced on the area covering 10% of the body surface of Wistar rats (n=15). The blood flow of the colon wall was continuously monitored for 15 min before and 45 min after the burn using OCTA and LDF. The colon wall was again studied on days 7 and 14 using the same OCTA and LDF techniques. At each time point (45 min, day 7 and 14), 5 animals were withdrawn from the experiment, the colon wall was taken for histological study. The colon wall samples from three control rats without thermal skin burns were also histologically investigated. During 45 min after the induction of the thermal burn, the in vivo OCTA and LDF techniques registered changes in intramural blood flow in the form of dropping of some arterioles and capillaries out of the general blood flow with concurrent activation of vascular shunts as a compensatory mechanism. Histologically, a marked edema of the submucosa, erythrocyte aggregation, and stasis in the capillary network were observed in this period. According to the OCTA and LDF data, the microcirculatory disorders in the colon were partially resolved by day 7, and by day 14 the analyzed indicators returned to the initial level. The data of the histological evaluation have shown that on day 7 after the burn induction, submucosal edema was absent, however, the signs of microcirculatory disorder and inflammatory changes remained. On day 14, the pathological changes in the tissues were not observed. The OCTA and LDF methods allowed us to establish experimentally that during the first 45 min thermal burn causes considerable disturbances of the blood flow in the colon wall, which normalizes only by day 14 if no therapy is administered. The obtained data on the mechanism of circulatory disorder development in the colon may become a basis for choosing therapy directed to prevention of intestine dysfunction in people with burns.

A Research Study on Histopathological Changes that are Seen in Lungs of Victims Who Died of Drowning

Drowning is considered to be the leading cause of death in water and the third most common cause of accidental death worldwide, with the highest drowning rates in developing countries. The WHO defines drowning as the process of experiencing respiratory impairment from submersion/immersion in liquid. For forensic experts, death in water is a multifaceted issue presenting a challenge to them. Since all the circumstances from natural death to homicide are possible in the water, critical examination and interpretation of all abnormal findings found during autopsy are of great importance.Drowning is a diagnosis of exclusion, based on ruling out all other causes of death via complete autopsy and toxicology. Drowning causes hypoxemia, loss of consciousness, apnea and ultimately cardiac arrest. Fluid aspiration results in lung injury and acute respiratory distress syndrome. Acute Respiratory Failure is the main component of drowning pathophysiology. Near drowning results in multiple complications including aspiration pneumonia which is often life-threatening. Hence the histopathological changes in the lungs provide good corroborative evidence of death due to drowning. Nevertheless, for the examined drowning signs, no high diagnostic certainty could be observed. However, these findings can increase their diagnostic value if forensic doctors take influencing factors into consideration.From the central record section of the Department of Forensic Medicine, Siddhartha Medical College, Vijayawada, Andhra Pradesh, about 80 medicolegal postmortem reports of death due to drowning in undecomposed bodies were selected in which one whole lung was sent for histopathological examination during the past two years i.e, 2020 - 2022. Parameters like Age, Sex and Marital Status were also studied. Histopathological examination of drowned lungs showed that congestion was seen in 92% of cases, oedema in 96% cases, dilatation of alveoli in 86% of cases, thinning of septa was seen in 84% of cases rupture of alveoli seen in 64% of cases and hemorrhage is seen in 46% of cases. Mostly males are affected and drowning deaths are seen more in 26 – 40 years age group. The histopathological investigations must be performed on all the organs of non-putrefied bodies with the aim of making the difference between death by drowning and other causes of death. The lung examinations can show over-distension of the alveoli, thinning of the alveolar septa and compression with narrowing of the capillary network.

Neutralization of Interleukin 1-beta is associated with preservation of thalamic capillaries after experimental traumatic brain injury.

Traumatic brain injury to thalamo-cortical pathways is associated with posttraumatic morbidity. Diffuse mechanical forces to white matter tracts and deep grey matter regions induce an inflammatory response and vascular damage resulting in progressive neurodegeneration. Pro-inflammatory cytokines, including interleukin-1β (IL-1β), may contribute to the link between inflammation and the injured capillary network after TBI. This study investigates whether IL-1β is a key contributor to capillary alterations and changes in pericyte coverage in the thalamus and cortex after TBI. Animals were subjected to central fluid percussion injury (cFPI), a model of TBI causing widespread axonal and vascular pathology, or sham injury and randomized to receive a neutralizing anti-IL-1β or a control, anti-cyclosporin A antibody, at 30 min post-injury. Capillary length and pericyte coverage of cortex and thalamus were analyzed by immunohistochemistry at 2- and 7-days post-injury. Our results show that early post-injury attenuation of IL-1β dependent inflammatory signaling prevents capillary damage by increasing pericyte coverage in the thalamus.

Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis.

Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima-media thickness was assessed with ultrasound. Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

Autocrine VEGF drives neural stem cell proximity to the adult hippocampus vascular niche.

The vasculature is a key component of adult brain neural stem cell (NSC) niches. In the adult mammalian hippocampus, NSCs reside in close contact with a dense capillary network. How this niche is maintained is unclear. We recently found that adult hippocampal NSCs express VEGF, a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that global and NSC-specific VEGF loss led to dissociation of NSCs and their intermediate progenitor daughter cells from local vasculature. Surprisingly, though, we found no changes in local vascular density. Instead, we found that NSC-derived VEGF supports maintenance of gene expression programs in NSCs and their progeny related to cell migration and adhesion. In vitro assays revealed that blockade of VEGF receptor 2 impaired NSC motility and adhesion. Our findings suggest that NSCs maintain their own proximity to vasculature via self-stimulated VEGF signaling that supports their motility towards and/or adhesion to local blood vessels.

Vascular Changes in Eyes with Post-Fever Retinitis Pre and Post Treatment Demonstrated Using Optical Coherence Tomography Angiography

ABSTRACT Purpose To document vascular changes in eyes with post-fever retinitis (PFR) pre and post treatment demonstrated using optical coherence tomography angiography (OCTA). Methods This is a retrospective observational case series wherein patients with PFR were retrospectively evaluated for changes in the retinal vasculature during the course of disease using OCTA. Results At presentation, OCTA revealed flow void areas in superficial and deep capillary plexus (SCP and DCP) corresponding to the areas of retinitis. Post treatment, OCTA showed a significant decrease in the flow void areas with the appearance of new capillary network in both SCP and DCP. The optical coherence tomography also demonstrated normalization of retinal architecture over time. It is speculated that the good visual outcome in PFR could be attributed to the normalization of retinal architecture and remodelling in retinal vasculature. Conclusion OCTA being non-invasive can be used to understand and quantify the extent of vascular remodelling in PFR.

Optical coherence tomography (OCT) and OCT-angiography in syndromic versus non-syndromic USH2A-associated retinopathy.

To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

Study of Macular Capillary network changes after branch retinal vein occlusion (BRVO) on optical coherence tomography angiography (OCT-A).

Study of Macular Capillary network changes after branch retinal vein occlusion (BRVO) on optical coherence tomography angiography (OCT-A).

Complement MASP-1 Modifies Endothelial Wound Healing.

Endothelial wound-healing processes are fundamental for the maintenance and restoration of the circulatory system and are greatly affected by the factors present in the blood. We have previously shown that the complement protein mannan-binding lectin-associated serine protease-1 (MASP-1) induces the proinflammatory activation of endothelial cells and is able to cooperate with other proinflammatory activators. Our aim was to investigate the combined effect of mechanical wounding and MASP-1 on endothelial cells. Transcriptomic analysis showed that MASP-1 alters the expression of wound-healing-related and angiogenesis-related genes. Both wounding and MASP-1 induced Ca2+ mobilization when applied individually. However, MASP-1-induced Ca2+ mobilization was inhibited when the treatment was preceded by wounding. Mechanical wounding promoted CREB phosphorylation, and the presence of MASP-1 enhanced this effect. Wounding induced ICAM-1 and VCAM-1 expression on endothelial cells, and MASP-1 pretreatment further increased VCAM-1 levels. MASP-1 played a role in the subsequent stages of angiogenesis, facilitating the breakdown of the endothelial capillary network on Matrigel®. Our findings extend our general understanding of endothelial wound healing and highlight the importance of complement MASP-1 activation in wound-healing processes.