Diameter Of Lymphatic Vessels Research Articles

Accuracy of Mirror Image Mapping of Lymphatic Tract for High-stage and Reoperative Lymphaticovenular Anastomosis: Intraoperative Analysis and Early Clinical Outcome.

Indocyanine green lymphography (ICGL) generally has a nonlinear pattern in advanced-stage lymphedema. Despite the lack of a linear pattern ICGL, lymphatic vessels have been discovered in several studies. The purpose of this work was to establish lymphatic mapping utilizing information from the contralateral limb and to illustrate the symmetry of lymphatic systems. Data were retrospectively collected from 81 patients who underwent lymphaticovenular anastomosis (LVA) using the contralateral mapping technique during 2018 to 2022. The sensitivity, specificity, accuracy, and negative and positive predictive values of this technique were calculated and analyzed. Lymphatic vessels were identified in 85.2% of the upper and 82.3% of the lower limb presumed sites using the contralateral mapping technique. The positive predictive value for successful LVA anastomosis was 93.8% for upper limb and 92.3% for lower limb cases. This mirror image technique's accuracy was 91.7% and 91.1%, for the upper limb and lower limb group, respectively. Between reoperative and new LVA cases, there was no statistically significant difference in the number, type, or diameter of lymphatic vessels or number of anastomoses. LVA with contralateral mapping technique is an effective method for patients with high-stage lymphedema with a nonlinear pattern on ICGL.

Lymphaticovenous anastomosis in rabbits: A novel live experimental animal model for supermicrosurgical training

BackgroundLymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. MethodsAn experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. ResultsThe patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. ConclusionThis study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.

Magnetic resonance lymphangiography: Establishing normal

BackgroundDespite an increased interest in visualizing the lymphatic vessels with magnetic resonance lymphangiography (MRL), little literature is available describing their appearance in nonlymphedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatic vessels appear and behave needs to be established. Therefore, in this study, MRL of individuals without a history of lymphatic disease was performed. MethodsA total of 25 individuals (15 women) underwent MRL of their lower limbs using a 3.0 T Philips magnetic resonance imaging scanner (Philips Medical Systems). The first nine participants were recruited to establish the concentration of gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged before and after interdigital forefoot GBCA injections at the optimized dose. Outcomes, including lymphatic vessel diameter, tortuosity, and frequency of drainage via particular drainage routes, were recorded. ResultsHealthy lymphatic vessels following the anteromedial pathway were routinely observed in post-contrast T1-weighted images (average tortuosity, 1.09 ± 0.03), with an average of 2.16 ± 0.93 lymphatic vessels with a diameter of 2.47 ± 0.50 mm crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of 10 vessels, the lymphatic signal, measured at the ankle, peaked 29 minutes, 50 seconds ± 9 minutes, 29 seconds after GBCA administration. No lymphatic vessels were observed in T2-weighted images. ConclusionsContrast-enhanced MRL reliably depicts the lymphatic vessels in the legs of healthy controls. Following interdigital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity, and drainage rate are readily obtainable and could be beneficial for detecting even subtle lymphatic impairment.

The Significance of Contrast-Enhanced Ultrasound in the Application of Lymphaticovenous Anastomosis.

Lymphaticovenous anastomosis (LVA) surgery is an effective treatment for lymphedema. Accurate evaluation and localization of the superficial lymphatic vessels before the operation is crucial for the success of the operation. Contrast-enhanced ultrasound (CEUS) is a new ultrasound technology, and its clinical application value in LVA surgery has not been established. This study aimed to assess the efficacy of CEUS in LVA surgery and provide a novel approach for the clinical assessment and localization of superficial lymphatic vessels. Retrospective analysis of imaging and surgical data was performed on 20 LVA patients. Among them, 10 cases underwent evaluation and localization using indocyanine green (ICG) lymphatic imaging (Group A), while 10 cases were evaluated and localized using CEUS (Group B). The differences in surgical data between the two groups were compared and analyzed. All 20 patients were female (mean age, 57.7 years ± 6.3 [SD]). CEUS demonstrated superior visualization and localization of superficial lymphatic vessels. The average diameter of lymphatic vessels identified in the CEUS group was significantly greater than that in the ICG group (0.78±0.06 vs. 0.52±0.05mm; P<0.001). The duration of operation in group B was significantly shorter than that in group A (4.47±0.37 vs. 6.70±0.45mm; P<0.001). The number of anastomosed lymphatic vessels in group B was less than that in group A [5.0(4.0, 6.0) vs. 9.5 (9.0, 11.3); P<0.001]. CEUS can serve as a viable alternative to ICG lymphatic imaging, facilitating improved lymphatic venous anastomosis surgery.

An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver.

The liver lymphatic system is essential for maintaining tissue fluid balance and immune function. The detailed structure of lymphatic vessels (LVs) in the liver remains to be fully demonstrated. The aim of this study is to reveal LV structures in normal and diseased livers by developing a tissue-clearing and coimmunolabeling protocol optimized for the tissue size and the processing time for three-dimensional (3-D) visualization and quantification of LVs in the liver. We showed that our optimized protocol enables in-depth exploration of lymphatic networks in the liver, consisting of LVs along the portal tract (deep lymphatic system) and within the collagenous Glisson's capsule (superficial lymphatic system) in different species. With this protocol, we have shown 3-D LVs configurations in relation to blood vessels and bile ducts in cholestatic mouse livers, in which LVs were highly dilated and predominantly found around highly proliferating bile ducts and peribiliary vascular plexuses in the portal tract. We also established a quantification method using a 3-D volume-rendering approach. We observed a 1.6-fold (P < 0.05) increase in the average diameter of LVs and a 2.4-fold increase (P < 0.05) in the average branch number of LVs in cholestatic/fibrotic livers compared with control livers. Furthermore, cholestatic/fibrotic livers showed a 4.3-fold increase (P < 0.05) in total volume of LVs compared with control livers. Our optimized protocol and quantification method demonstrate an efficient and simple liver tissue-clearing procedure that allows the comprehensive analysis of liver lymphatic system.NEW & NOTEWORTHY This article showed a comprehensive 3-D-structural analysis of liver lymphatic vessel (LV) in normal and diseased livers in relation to blood vessels and bile ducts. In addition to the LVs highly localized at the portal tract, we revealed capsular LVs in mouse, rat, and human livers. In cholestatic livers, LVs are significantly increased and dilated compared with normal livers. Our optimized protocol provides detailed spatial information for LVs remodeling in normal and pathological conditions.

Modified Preparatory Intravascular Stenting Technique in Super-microsurgical Lymphaticovenular Anastomosis for the Treatment of Lymphedema.

Clinical studies have reported that lymphaticovenular anastomosis (LVA) is more effective for early-stage lymphedema. However, the diameter of lymphatic vessels in early-stage lymphedema is thin (only about 0.3 mm). In this article, we report a modified preparatory intravascular stenting technique (PIST) for LVA with smaller lymphatic vessels and present the results of its application for the treatment of secondary lymphedema. In this technique, a 9-0 nylon thread is inserted into the target lymphatic vessel. Then, the thread is pulled until its tip has entered the lymphatic vessel. After that, the thread is allowed to proceed into the lumen by pushing it. Finally, with the nylon in place, the lymphatic vessel is transected and the lumen is secured. In this report, we investigated the surgical time for LVA between 10 patients who underwent LVA with modified PIST (group A) and another group of 10 patients who underwent LVA without the technique (group B). Lymphatic lumen was secured at all sites where indocyanine green lymphangiography confirmed lymphatic flow. The average outer diameter of lymphatic vessels in group A and B were 0.36 mm and 0.53 mm, respectively. The average surgical time for LVA in group A was 136 minutes, which was significantly shorter than the 187 minutes in group B. Our results indicated that modified PIST can help secure the lymphatic lumen even when the lymphatic vessels are thin. As a result, this technique can significantly reduce the surgical time for this procedure.

Introducing the bungee-IVaS technique: A modification for safer and simpler intravascular stenting in supermicrosurgery

Supermicrosurgery has revolutionized the field of reconstructive surgery by enabling surgeons to perform challenging procedures that were previously unattainable. Lymphaticovenous anastomosis (LVA) for the treatment of lymphedema is a commonly performed procedure using this technique. However, the small diameter and thin-walled nature of lymphatic vessels limit the use of microsurgical forceps instrumentation into the lumen to prevent trauma, increasing the risk of inadvertent catching of the vessel backwall during anastomosis.

Borneol-driven meningeal lymphatic drainage clears amyloid-β peptide to attenuate Alzheimer-like phenotype in mice.

Rationale: The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aβ and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aβ from the brain. Methods: We investigated the effect of borneol on meningeal lymphatic clearance of macromolecules with different molecular weights (including Aβ) in the brain. To further investigate the mechanism of borneol regulating meningeal lymphatic drainage, immunofluorescence staining, western blotting, ELISA, RT-qPCR, and Nitric Oxide assay kits were used. The cognitive function of AD mice after borneol treatment was evaluated using two behavioral tests: open field (OF) and Morris water maze (MWM). Results: This study discovered that borneol could accelerate the lymphatic clearance of Aβ from the brain by enhancing meningeal lymphatic drainage. Preliminary mechanism analysis revealed that borneol could improve the permeability and inner diameter of lymphatic vessels, allowing macromolecules to drain into the cervical lymph nodes (CLNS) and then be transported to the lymphatic circulation. To speed up the clearance of macromolecules, borneol also stimulated lymphatic constriction by lowering the level of nitric oxide in the meninges. In addition, borneol stimulated lymphangiogenesis by increasing the levels of FOXC2, VEGFC, and LYVE-1 in the meninges, which promoted the clearance rates of macromolecules. Borneol improved meningeal lymphatic clearance not only for Aβ but also for other macromolecular polymers (molecular weight in the range of 2 KD - 45 KD. Borneol ameliorated cognitive deficits and alleviated brain Aβ burden in Aβ-injected mice. Conclusions: Our findings not only provide a strategy to regulate lymphatic clearance pathways of macromolecules in the brain, but also new targets and ideas for treating neurodegenerative diseases like AD. Furthermore, our findings indicate that borneol is a promising therapeutic drug for AD.

Characteristic Features of Deep Brain Lymphatic Vessels and Their Regulation by Chronic Stress.

Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain. However, it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life events. We used tissue clearing techniques, immunostaining, light-sheet whole-brain imaging, confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain parenchyma. Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events. Western blotting and coimmunoprecipitation were used to provide mechanistic insights. We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex, cerebellum, hippocampus, midbrain, and brainstem. Furthermore, we showed that deep brain lymphatic vessels can be regulated by stressful life events. Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala. No changes were observed in prefrontal cortex, lateral habenula, or dorsal raphe nucleus. Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus. Mechanistically, chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms. Our results provide new insights into the characteristic features of deep brain lymphatic vessels, as well as their regulation by stressful life events.

Networked lymphatic endothelial cells in a transplanted cell sheet contribute to form functional lymphatic vessels

This study evaluated whether cell sheets containing a network of lymphatic endothelial cells (LECs) promoted lymphangiogenesis after transplantation in vivo. Cell sheets with a LEC network were constructed by co-culturing LECs and adipose-derived stem cells (ASCs) on temperature-responsive culture dishes. A cell ratio of 3:2 (vs. 1:4) generated networks with more branches and longer branch lengths. LEC-derived lymphatic vessels were observed 2 weeks after transplantation of a three-layered cell sheet construct onto rat gluteal muscle. Lymphatic vessel number, diameter and depth were greatest for a construct comprising two ASC sheets stacked on a LEC/ASC (3:2 ratio) sheet. Transplantation of this construct in a rat model of femoral lymphangiectomy led to the formation of functional lymphatic vessels containing both transplanted and host LECs. Further development of this technique may lead to a new method of promoting lymphangiogenesis.

Negative-Pressure Wound Therapy Induces Lymphangiogenesis in Murine Diabetic Wound Healing.

Decreased lymphangiogenesis contributes to impaired diabetic wound healing. Although negative-pressure wound therapy (NPWT) has been shown to be effective in the treatment of recalcitrant wounds, its impact on lymphangiogenesis remains to be elucidated. In this study, the authors investigate the mechanisms of lymphangiogenesis following NPWT treatment of diabetic murine wound healing. Full-thickness dorsal skin wounds (1 × 1 cm 2 ) were excised on 30 db/db mice. The mice were either treated with occlusive covering (control group, n = 15), or received a 7-day treatment of continuous NPWT at -125 mmHg (NPWT group, n = 15). The wounds were photographed on days 0, 7, 10, 14, 21, and 28. Wound tissue was harvested on days 10, 14, 21, and 28 for quantitative analysis. Functional analysis of lymphatic drainage was performed on days 14 and 28 with Evans blue dye tracing. Lymphatic density and diameter, as visualized through podoplanin probing, was significantly higher in the NPWT group compared to the control group ( P < 0.001). NPWT up-regulated the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) at the protein level ( P = 0.04), and significant differences were noted in lymphatic density as assessed by LYVE-1 staining ( P = 0.001). Leukocyte infiltration was significantly higher in the NPWT group ( P = 0.01). A higher speed of wound closure ( P < 0.0001) and greater wound bed thickness ( P < 0.0001) were noted in the NPWT group compared to the control group. NPWT increased the lymphatic vessel density and diameter with LYVE-1 up-regulation. NPWT therefore plays a positive role in lymphangiogenesis in diabetic wound healing. The authors' study investigates the association of NPWT and lymphatics and underlines the importance of a more in-depth investigation of the role of lymphatic vessels in wound healing.

Lymphaticovenular anastomoses training model for multiple stages of lymphedema by using efferent lymphatic plexus of the mesenteric lymph node of rats.

Lymphaticovenular anastomosis (LVA) has transformed lymphedema treatment and has become an important part of the surgical therapy. LVA requires supermicrosurgical skills and unique nontraumatic techniques as the lymphatic vessel diameter of varies with the progression of lymphedema from 0.3 to 0.8 mm. However, even though several supermicrosurgical vessel anastomosis training models have been reported, only few focus on LVA including both various sizes of lymphatic vessels and lymphatic dissection. We report the establishment of a novel in-vivo LVA training model using the rat efferent lymphatic plexus of the mesenteric lymph node. Lymphatic vessels in the efferent lymphatic plexus of the mesenteric lymph node and mesenteric veins of 10 male Wistar rats, 572-850 g, were used for LVA in an intima-to-intima coaptation manner using 12-0 nylon suture with 4-6 stitches in an end-to-end fashion. Postoperative patency was evaluated with indigo carmine blue after completion of anastomosis. Diameters of lymphatic vessels in the plexus and recipient veins were measured. The diameters of lymphatic vessels in efferent lymphatic plexus of the mesenteric lymph nodes and mesenteric veins used as recipients were measured in all 10 male rats. The mean number of lymphatic vessels included in efferent lymphatic plexus of the mesenteric lymph nodes was 7.5 (range, 5-11) and the mean diameter of the lymphatic vessels was 0.34 mm (range, 0.1-1.2 mm). The mean diameter of lymphatic vessels used for LVA was 0.46 mm (range, 0.25-0.7 mm). The mean diameter of the recipient veins was 0.49 mm (range, 0.35-0.7 mm). The postoperative patency rate after LVA was 100% (10/10). We reported the establishment of LVA model involving the use of the efferent lymphatic plexus of the mesenteric lymph node and mesenteric veins in rats.

The Lymphangiogenic Effect of Continuous Negative Pressure Wound Therapy in Murine Incisional Wounds

INTRODUCTION: The effects of negative pressure wound therapy (NPWT) on the vascular system are well described. Despite the significant role of the lymphatics in wound healing, the impact of NPWT on lymphangiogenesis remains to be elucidated. Here, we studied the effects of NPWT on lymphatic regeneration in a murine incisional wound model. METHODS: Thirty diabetic mice (db/db) received dorsal incisional skin wounds and were treated with occlusive covering (Control, n = 15) or continuous NPWT (24 hours × 7 days, –125 mmHg; NPWT, n = 15). The wounds were monitored for 28 days, tissue was harvested on day 10 for analysis, and Evans Blue staining of lymphatic drainage was performed at 28 days. RESULTS: NPWT was associated with increased lymphatic density, as visualized using the lymphatic-vessel specific Podoplanin (39.6 ± 19.9 vs 11.5 ± 5.9 PDPN+/HPF; p < 0.001) and LYVE-1 (24.8 ± 9.1 vs 13.7 ± 7.9 LYVE-1+/HPF; p = 0.01). Lymphatic vessel diameter was higher in the NPWT group (27.5 ± 9.0 vs 12.4 ± 2.2 μm; p < 0.001). Western blotting showed that NPWT upregulated the expression of LYVE-1 at the protein level (p = 0.03). On functional assessment of the lymphatics, the NPWT exhibited a larger area of Evans Blue positivity at all timepoints (0, 5, 10, 15, 20, 25 and 30 minutes). CONCLUSION: Our findings indicate that NPWT significantly modulates lymphatic regeneration in incisional wounds. The effects were shown to occur at the protein level, resulting in structural and functional improvement. This highlights the potential of NPWT to therapeutical stimulate lymphatic growth and drainage in wound healing or in conditions such as lymphedema.

A narrative review on the role of carbon nanoparticles in oncology.

The lymphatic system is the first site of metastasis for most tumors and is a common reason for the failure of cancer therapy. The lymphatic system's anatomical properties make it difficult to deliver chemotherapy agents at therapeutic concentrations while avoiding systemic toxicity. Carbon nanoparticles offer a promising alternative for identifying and transporting therapeutic molecules. The larger diameter of lymphatic vessels compared to the diameter of blood vessels, allows carbon nanoparticles to selectively enter the lymphatic system once administered subcutaneously. Carbon nanoparticles stain tumor-draining lymph nodes black following intratumoral injection, making them useful in sentinel lymph node mapping. Drug-loaded carbon nanoparticles allow higher concentrations of chemotherapeutics to accumulate in regional lymph nodes while decreasing plasma drug accumulation. The use of carbon nanoparticles for chemotherapy delivery has been associated with lower mortality, fewer histopathology changes in vital organs, and lower serum concentrations of hepatocellular enzymes. This review will focus on the ability of carbon nanoparticles to target the lymphatics as well as their current and potential applications in sentinel lymph node mapping and oncology treatment regimens. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.

Lymphaticovenous Anastomosis for Treating Secondary Lower Limb Lymphedema in Older Patients-A Retrospective Cohort Study.

Despite an increased incidence of secondary lower limb lymphedema (LLL) and severity of comorbidities with age, the impact of age on the effectiveness of lymphaticovenous anastomosis (LVA) in the older patients remains unclear. Methods: This retrospective cohort study enrolled older patients (age > 65 years) with secondary unilateral LLL. All patients underwent supermicrosurgical LVA. Demographic data and intraoperative findings including lymphatic vessel (LV) diameter, LV functionality (indocyanine green-enhanced and Flow positivity), and lymphosclerosis classification were recorded. Magnetic resonance volumetry was used for measuring preoperative and postoperative volume changes at 6 months and one year after LVA as primary and secondary endpoints. Results: Thirty-two patients (29 females/3 males) with a median age of 71.0 years [range, 68.0 to 76.3] were enrolled. The median duration of lymphedema was 6.4 [1.0 to 11.7] years. The median LV diameter was 0.7 [0.5 to 0.8] mm. The percentage of ICG-enhanced and Flow-positive LVs were 89.5% and 85.8%, respectively. The total percentage of suitable LVs (s0 and s1) for LVA based on lymphosclerosis classification was 75.9%. There were significant six-month and one-year post-LVA percentage volume reductions compared to pre-LVA volume (both p < 0.001). A significant reduction in cellulitis incidence was also noted after LVA (p < 0.001). No surgical or postoperative complications were found. Conclusion: Relief of secondary LLL was achievable through LVA in older patients who still possessed favorable LV characteristics, including larger LV diameters as well as a high proportion of functional LVs with a low grade of lymphosclerosis.

ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis.

The capacity of ADAMTS3 to cleave pro-VEGFC into active VEGFC able to bind its receptors and to stimulate lymphangiogenesis has been clearly established during embryonic life. However, this function of ADAMTS3 is unlikely to persist in adulthood because of its restricted expression pattern after birth. Because ADAMTS2 and ADAMTS14 are closely related to ADAMTS3 and are mainly expressed in connective tissues where the lymphatic network extends, we hypothesized that they could substitute for ADAMTS3 during adulthood in mammals allowing proteolytic activation of pro-VEGFC. Here, we demonstrated that ADAMTS2 and ADAMTS14 are able to process pro-VEGFC into active VEGFC as efficiently as ADAMTS3. In vivo, adult mice lacking Adamts2 developed skin lymphedema due to a reduction of the density and diameter of lymphatic vessels, leading to a decrease of lymphatic functionality, while genetic ablation of Adamts14 had no impact. In a model of thermal cauterization of cornea, lymphangiogenesis was significantly reduced in Adamts2- and Adamts14-KO mice and further repressed in Adamts2/Adamts14 double-KO mice. In summary, we have demonstrated that ADAMTS2 and ADAMTS14 are as efficient as ADAMTS3 in activation of pro-VEGFC and are involved in the homeostasis of the lymphatic vasculature in adulthood, both in physiological and pathological processes.

Drainage of senescent astrocytes from brain via meningeal lymphatic routes

Recent progress on the central lymphatic system has greatly increased our understanding of how the brain maintains its own waste homeostasis. Here, we showed that perivascular spaces and meningeal lymphatic vessels form a functional route for clearance of senescent astrocytes from the aging brain. Blocking meningeal lymphatic drainage by ligation of the deep cervical lymph nodes impaired clearance of senescent astrocytes from brain parenchyma, subsequently increasing neuroinflammation in aged mice. By contrast, enhancing meningeal lymphatic vessel diameter by a recombinant adeno-associated virus encoding mouse vascular endothelial growth factor-C (VEGF-C) improved clearance of senescent astrocytes and mitigated neuroinflammation. Mechanistically, VEGF-C was highly expressed in senescent astrocytes, contributing themselves to migrate across lymphatic vessels along C–C motif chemokine ligand 21 (CCL21) gradient by interacting with VEGF receptor 3. Moreover, intra-cisternal injection of antibody against CCL21 hampered senescent astrocytes into the lymphatic vessels and exacerbated short memory defects of aged mice. Together, these findings reveal a new perspective for the meningeal lymphatics in the removal of senescent astrocytes, thus offering a valuable target for therapeutic intervention.

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis.

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.

The accuracy of lymphatic ultrasound in measuring the lymphatic vessel size in lower limb lymphedema patients

Lymphatic ultrasound is a newly developed method to observe the lymphatic vessels. In this study, we compared the diameter of lymphatic vessels observed on preoperative ultrasound with the actual lymphatic diameter (LD) of lymphatic vessels observed intraoperatively. The study included 32 lower limbs in 17 patients with lower limb lymphedema. Lymphatic ultrasound was performed using a commonly used ultrasound device, Noblus ultrasound system, with an 18MHz linear probe on preoperative day 1. We tracked the lymphatic vessels along the great saphenous vein, at the lateral calf, and at the lateral thigh, based on the lymphosome principle. We measured the cross-sectional height (CSH) and the cross-sectional width (CSW) of lymphatic vessels using ultrasound at the incision sites. Intraoperatively, we measured the diameter of the lymphatic vessel. Based on lymphatic degeneration, lymphatic vessels were categorized into four types using the normal-, ectasis-, contraction-, and sclerosis-type (NECST) classification. We evaluated 68 lymphatic vessels. The mean CSH, CSW, and LD were 0.65±0.35mm, 1.3±0.41mm, and 0.79±0.35mm, respectively. The correlation coefficient between the CSH and the LD was 0.36 and that between the CSW and LD was 0.24. A significant difference was observed in CSH between the ectasis and contraction types (p=0.0025). We can somehow predict the size of the lymphatic vessels with CSH in the lymphatic ultrasound, whereas CSW is not reliable.

Lymphaticovenous Anastomosis for Age-Related Lymphedema.

Introduction: Primary lymphedema is usually caused by intrinsic disruption or genetic damage to the lymphatics but may also be the result of age-related deterioration of the lymphatics. The aims of this study were to determine the characteristics of age-related lymphedema and to assess the effectiveness of lymphaticovenous anastomosis (LVA) in its treatment. Methods: Eighty-six patients with primary lymphedema affecting 150 lower limbs were divided into three groups according to whether the age of onset was younger than 35 years, 35–64 years, or 65 years or older. Indocyanine green (ICG) lymphography was performed, followed by LVA surgery. ICG lymphography images were visually classified according to whether the pattern was linear, low enhancement (LE), distal dermal backflow (dDB), or extended dermal backflow (eDB). The lower extremity lymphedema (LEL) index score was calculated before and after LVA. Lymphatic vessel diameter and detection rates were also recorded. Results: In the ≥65 group, the lymphedema was bilateral in 54 patients and unilateral in 1 patient. There was statistically significant deterioration in the LEL index score with progression from the linear, LE, dDB through to the eDB pattern in the ≥65 group. The lymphatic vessel diameter was significantly greater in the ≥65 group. The rate of improvement was highest in the ≥65 group. Conclusion: Age-related lymphedema was bilateral and deterioration started distally. The lymphatic vessels in patients with age-related lymphedema tended to be ectatic, which is advantageous for LVA and may increase the improvement rate.