Dorsal Vessels Research Articles

Anatomical Basis and Clinical Application of the First Metatarsal Proximal Perforator-Based Neurocutaneous Vascular Flap.

Forefoot defects caused by accidents are very common, but their reconstruction remains a substantial challenge for plastic surgeons. The purpose of this study is to determine the anatomical structure of the first metatarsal proximal perforator-based flap and to propose its clinical application. The study was divided into two parts: an anatomical study and a clinical application. Thirty preserved lower limbs injected with red latex were chosen for observation, and the following were recorded: the course and distribution of the medialis dorsalis pedis cutaneous nerve; the origin, course, branching and distribution of the first metatarsal proximal perforator; and the communication of the perforator and the dorsal medial vessels. Clinically, six cases of forefoot skin defects were reconstructed with the first metatarsal proximal perforator-based neurocutaneous vascular flap. The medialis dorsalis pedis cutaneous nerve mainly arose from the medial branch of the superficial peroneal nerve and proceeded forward for a distance of 2.5 ± 0.4 cm under the surface of the inferior extensor retinaculum; then, the nerve divided into the medial dorsal branch and the first and second dorsal metatarsal branches. The first metatarsal proximal perforator-based neurocutaneous vessels were multisegmented and multisourced, and the first branch was closely related to the operative procedure. In terms of the clinical application, all flaps of the six cases survived completely with good appearance, texture and elasticity. The first metatarsal proximal perforators present as constant. The first metatarsal proximal perforator-based neurocutaneous vascular flap may become a useful supplemental material for the reconstruction of forefoot defects. Clin. Anat., 33:653-660, 2020. © 2019 Wiley Periodicals, Inc.

Neural stimulations regulate the infiltration of immune cells into the CNS.

The systemic regulation of immune reactions by the nervous system is well studied and depends onthe release of hormones. Some regional regulations of immune reactions, on the other hand, depend on specific neural pathways. Better understanding of these regulations will expand therapeutic applications for neuroimmune and organ-to-organ functional interactions. Here, we discuss one regional neuroimmune interaction, the gateway reflex, which converts specific neural inputs into local inflammatory outputs in the CNS. Neurotransmitters released by the inputs stimulate specific blood vessels to express chemokines, which serve as a gateway for immune cells to extravasate into the target organ such as the brain or spinal cord. Several types of gateway reflexes have been reported, and each controls distinct CNS blood vessels to form gateways that elicit local inflammation, particularly in the presence of autoreactive immune cells. For example, neural stimulation by gravity creates the initial entry point to the CNS by CNS-reactive pathogenic CD4+ T cells at the dorsal vessels of fifth lumbar spinal cord, while pain opens the gateway at the ventral side of blood vessels in the spinal cord. In addition, it was recently found that local inflammation by the gateway reflex in the brain triggers the activation of otherwise resting neural circuits to dysregulate organ functions in the periphery including the upper gastrointestinal tract and heart. Therefore, the gateway reflex represents a novel bidirectional neuroimmune interaction that regulates organ functions and could be a promising target for bioelectric medicine.

Mutation ephb4 responsable de malformation anévrysmale de la veine de Galien

Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all pediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients who presented this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of EPHB4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, wich is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild type but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation–arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

In Vivo Visualization of Vasculature in Adult Zebrafish by Using High-Frequency Ultrafast Ultrasound Imaging.

Zebrafish has been recently considered an ideal vertebrate for studying developmental biology, genetics, particularly for modeling tumorigenesis, angiogenesis, and regeneration in vivo. However, when a zebrafish matures completely, its body loses transparency, thus making conventional optical imaging techniques difficult for imaging internal anatomy and vasculature. Acoustic wave penetration outperforms optical methods, high-frequency (>30 MHz) ultrasound (HFUS) was consequently an alternative imaging modality for adult zebrafish imaging, particularly for echocardiography However, visualizing peripheral vessels in a zebrafish by using conventional HFUS is still difficult. In the present study, high-frequency micro-Doppler imaging (HFμDI) based on ultrafast ultrasound imaging was proposed for zebrafish dorsal vascular mapping in vivo. HFμDI uses a 40-MHz ultrasound transducer, which is an ultrafast ultrasound imaging technology with the highest frequency available currently. Blood flow signals were extracted using an eigen-based clutter filter with different settings. Experiments were performed on an 8-month-old wild-type AB-line adult zebrafish. Blood vessels, including intersegmental vessels, parachordal vessel, dorsal longitudinal anastomotic vessel, and dorsal aorta, from the dorsal side of the zebrafish were clearly observed in two-dimensional (2-D) and 3-D HFμDI. The maximum image depth of HFμDI and the minimal diameter of vessel can be detected were 4 mm and 36μm, respectively; they were determined without any use of microbubbles. The maximum flow velocity range was approximately 3-4 mm/s on the dorsal vessels of the adult zebrafish. Compared with conventional ultrasound Doppler imaging, HFμDI exhibited superior small vessel imaging.

CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart

Proper coronary vasculature development is essential for late-embryonic and adult heart function. The developmental regulation of coronary embryogenesis is complex and includes the coordinated activity of multiple signaling pathways. CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF-C signaling, which is also required for coronary vasculature formation. However, whether CCBE1 plays a similar role during coronary vasculature development is still unknown. Here, we investigate the coronary vasculature development in Ccbe1 mutant embryos. We show that Ccbe1 is expressed in the epicardium, like Vegf-c, and also in the sinus venosus (SV) at the stages of its contribution to coronary vasculature formation. We also report that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts from the SV endocardium at the dorsal cardiac wall. This disruption of coronary formation correlates with abnormal processing of VEGF-C propeptides, suggesting VEGF-C-dependent signaling alteration. Moreover, Ccbe1 loss-of-function leads to the development of defective dorsal and ventral intramyocardial vessels. We also demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery (CA) stem formation. CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics 247:1135-1145, 2018. © 2018 Wiley Periodicals, Inc.

Applied anatomy of the first metatarsal proximal perforator-based neurocutaneous vascular flap

Objective To explore the anatomical characteristics of mediate dorsal pedal cutaneous nerve and its nutritional vessels to provide anatomical basis of the perforator pedicle flap based on the medial dorsal pedal neurocutaneous vessels for repairing the forefoot soft-tissue defects. Methods From December, 2016 to April, 2017, the following contents were investigated in 30 adult feet specimens perfused with red latex: ①The course, branches and distribution of the medial dorsal pedal cutaneous nerve. ②The origin, course, branches and distribution of the nutrient vessels of the medial dorsal pedal neurocutaneous vessels. Mimic operation was performed on 1 fresh specimen. Results ①The mediate dorsal pedal cutaneous nerve mainly arose from the medial branch of the superficial peroneal nerve and processed forward for a distance of (2.5±0.4) cm under the surface of the inferior extensor retinaculum, and then divided into the mediate dorsal branch, the 1st and 2nd dorsal metatarsal branch over part of the dorsal pedal and digital skin. ②The medial dorsal pedal neurocutaneous vessels were multiple segmental and polyphyletic, mainly include dorsalis pedis artery proximal perforator, the first metatarsal proximal perforator, the tibial proper plantar digital artery of the great toe and the perforater of the second toe web artery, of which the first metatarsal proximal perforator was most associated with operating methods. The first metatarsal proximal perforator perforate through the deep fascia to the subcutaneous area within the range of 1.0-2.0 cm near the proximal first plantar gap, the piercing point of which on deep fascia was constant,and the anatomical plane of the first metatarsal proximal perforator was higher than that of both the perforator of the toe web artery and the tibial proper plantar digital artery of the great toe. The first metatarsal proximal perforator divide into a large number of branches, which closely anastomose with adjacent perforators and other medial dorsal pedal neurocutaneous vessels. ③Simulated surgery showed that the first metatarsal proximal perforation pedicle flap to meet the forefoot soft tissue defect repair. Conclusion The first metatarsal proximal perforator is constant in piercing point and reliable in blood supply, and it have a higher anatomical plane than that of both the perforator of the toe web artery and the tibial proper plantar digital artery of the great toe. The first metatarsal proximal perforator-based medial dorsal pedal neurocutaneous vascular flap can be transferred to repair the soft-tissue defects of forefoot. Key words: First metatarsal proximal perforator; Medical dorsal pedal cutaneous nerve; Surgical flaps; Applied anatomy

Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation.

See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

Antiangiogenic and Toxic Effects of Genistein, Usnic Acid, and Their Copper Complexes in Zebrafish Embryos at Different Developmental Stages.

Angiogenesis plays a major role in the normal embryonic development and in diseases such as cancer. Drugs that control angiogenesis are an alternative way to tackle this disease. The polyphenols usnic acid (3), genistein (5), and daidzein (6) were tested for antiangiogenic and unwanted effects in zebrafish embryos whose blood vessel system resembles that of mammals. The established tyrosine kinase inhibitors axitinib (1) and tyrphostin AG490 (2) were included for comparison. All compounds except 6 caused distinct antiangiogenic effects such as a concentration-dependent reduction of intersegmental vessels, dorsal longitudinal anastomotic vessels, subintestinal veins and secondary sprouts. As side effects, pericardial oedema and the impairment of blood flow were observed. Usnic acid (3), genistein (5) and Cu(II)-genisteinate (7) gave rise to a curvature of the spine. Compounds 5 and 7 also induced cell death in the head of the embryos at higher doses. All effects were more pronounced when the compounds had been applied at an early stage (24 hpf) rather than at 48 hpf. The copper complexes 4 and 7 showed a stronger antiangiogenic effect than the free ligands 3 and 5. The genistein complex 7 was antiangiogenic at doses so low that side effects were tolerable, and thus it may be a potential anticancer drug candidate.

Gateway reflexes: A new paradigm of neuroimmune interactions

AbstractThe immune system is affected considerably by the physical environment. The molecular mechanisms that regulate this connection are not well understood. Because neural activities sense the environment, it has been hypothesized that neural signals transduce environmental stimulations into immune responses. Recently, we discovered that regional neural activations change the dynamics of immune cell migration through the activity of endothelial cells by using a multiple sclerosis model, experimental autoimmune encephalomyelitis. More specifically, we identified the dorsal vessels of the fifth lumbar (L5) spinal cord as the initial entry site of pathogenic T cells. This entry site was defined by the activation of sensory neurons innervating from the soleus muscles, which are the main antigravity muscles. The resulting sensory neural activation created a gateway through the activation of regional sympathetic pathways to increase the expression of chemokines at the dorsal vessels of the L5 spinal cord, attracting autoreactive pathogenic T cells. In other experiments, we activated different regional neurons by electric pulses or pain sensation and discovered that gateways for immune cells, including autoreactive pathogenic T cells, are dependent on the site of the regional neural activation, particularly the sensory–sympathetic crosstalk. We termed these neuroimmune interactions as “gateway reflexes.” In the present review, we discuss details of the gateway reflex.

The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish.

Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish. Furthermore, chromatin immunoprecipitation experiments confirmed that Bach1 occupied the TCF/LEF-binding site of the VEGF promoter in human umbilical vein endothelial cells (HUVECs). Bach1 inhibited VEGF transcription by recruiting histone deacetylase 1 (HDAC1) to the VEGF promoter in HUVECs. Exogenous administration of VEGF or IL-8 partially rescued Bach1-driven antiangiogenic functions in HUVECs. Taken together, these observations indicate that Bach1 suppresses the developmental angiogenesis of zebrafish and that this function is associated with declines in Wnt/β-catenin signaling and VEGF and IL-8 expression.

Blood circulation in the ascidian tunicate Corella inflata (Corellidae).

The body of the ascidian tunicate Corella inflata is relatively transparent. Thus, the circulatory system can be visualized by injecting high molecular weight fluorescein labeled dextran into the heart or the large vessels at the ends of the heart without surgery to remove the body wall. In addition, after staining with neutral red, the movement of blood cells can be easily followed to further characterize the circulatory system. The heart is two gently curved concentric tubes extending across the width of the animal. The inner myocardial tube has a partial constriction approximately in the middle. As in other tunicates, the heart is peristaltic and periodically reverses direction. During the branchial phase blood leaves the anterior end of the heart by two asymmetric vessels that connect to the two sides of the branchial basket. Blood then flows in both transverse directions through a complex system of ducts in the basket into large ventral and dorsal vessels which carry blood back to the visceral organs in the posterior of the animal. During the visceral phase blood leaves the posterior end of the heart in two vessels that repeatedly bifurcate and fan into the stomach and gonads. Blood velocity, determined by following individual cells in video frames, is high and pulsatory near the heart. A double peak in velocity at the maximum may be due to the constriction in the middle of the heart tube. Blood velocity progressively decreases with distance from the heart. In peripheral regions with vessels of small diameter blood cells frequently collide with vessel walls and cell motion is erratic. The estimated volume of blood flow during each directional phase is greater than the total volume of the animal. Circulating blood cells are confined to vessels or ducts in the visible parts of the animal and retention of high molecular weight dextran in the vessels is comparable to that seen in vertebrates. These are characteristics of a closed circulatory system.

A Three-Dimensional Micro-Computed Tomographic Study of the Intraosseous Lunate Vasculature: Implications for Surgical Intervention and the Development of Avascular Necrosis.

The purpose of this study was to use micro-computed tomography to demonstrate the intraosseous vascularity of the lunate within a three-dimensional orientation to identify areas of greatest perfusion and define vascular "safe zones" for surgical intervention. Fourteen upper extremities were injected with a lead-based contrast agent. The lunates were harvested and scanned using a micro-computed tomography scanner. The intraosseous vascularity was incorporated into a three-dimensional image. Vessel number, diameter, distribution, and pattern were evaluated and analyzed. Vascularity of all specimens was projected onto one representative lunate to identity areas of higher and lower vascularity. Twelve specimens had nutrient vessels entering the bone from volar and dorsal; two specimens had no dorsal vessels. The intraosseous vascularity could be classified according to the Y, I, and X patterns described by Gelberman et al. Average number and diameter of vessels were 2.3 and 118.1 μm, respectively, for volar; and 1.4 and 135.8 μm, respectively, for dorsal. The long axis of the lunate showed the highest vascularity on both axial and lateral views. Lower vascularity was observed in the dorsoradial and volar-ulnar quadrants on the axial view, and in the proximal part on the lateral view. Lunate shape was not associated with an increase or decrease in nutrient vessels or vascular pattern. Vascular safe zones were identified, allowing for potentially safer surgical interventions to the lunate. Volar approaches to the lunate may result in localized ischemia in a subset of patients with absent dorsal nutrient vessels. This study may help to better define patients at risk for Kienböck disease.

Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis)

Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10-13 to 10-3 M) and blockade with L-NAME (10-5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Integration of vascular systems between the brain and spinal cord in zebrafish

Cerebral and spinal vascular systems are organized individually, and they then conjugate at their border, through the integration of basilar artery and vertebral arteries. Zebrafish (Danio rerio) is an ideal organism for studying early vascular development, and the precise procedure of cranial and truncal vascular formation has been previously demonstrated using this model. However, the stepwise process of the integration between the brain and spinal cord has not been clearly elucidated. In this study, we describe the integration of the independent vascular systems for the brain and spinal cord, using transgenic zebrafish expressing enhanced green fluorescent protein in endothelial cells. Initially, basilar artery and primordial hindbrain channels, into which internal carotid arteries supplied blood, were connected with dorsal longitudinal anastomose vessels, via the first intersegmental artery. This initial connection was not influenced by flow dynamics, suggesting that vascular integration in this region is controlled by genetic cues. Vertebral arteries were formed individually as longitudinal vessels beneath the spinal cord, and became integrated with the basilar artery during subsequent remodeling. Furthermore, we confirmed the basal vasculature was well conserved in adult zebrafish. Observations of vascular integration presented herein will contribute to an understanding of regulatory mechanisms behind this process.

Adipose-derived stem cells ameliorate erectile dysfunction after cavernous nerve cryoinjury.

Erectile dysfunction is a common complication following cryotherapy for prostate cancer. In this study, we investigated the efficacy of adipose-derived stem cells (ADSC) in improving erectile function in a rat model of cavernous nerve (CN) cryoinjury and the possible mechanisms. Male rats were intracavernous (IC) injected with EdU-labeled ADSC after bilateral CN cryoinjury. Penile tissues were harvested for histology and protein level detection at 1 and 4weeks after ADSC administration. Erectile function was assessed prior to tissue harvest. We found that erectile function was significantly improved after ADSC treatment via promoting nNOS-positive nerve regeneration and cavernous tissue recovery. The expression of cleaved caspase 3 (an apoptotic marker) reduced after ADSC treatment. Although few EdU-labeled ADSCs were visualized within the penis 4weeks after administration, plenty of EdU-labeled ADSCs were found around penile dorsal vessels and nerves 1week after treatment. Furthermore, three neurotrophic factors (NGF, VEGF, and Neurturin) were significantly decreased in Cryo group, and were partially recovered 1week after ADSC injection. These results suggested that IC injection of ADSC resulted in substantial recoveries of erectile function after CN cryoinjury. The effects may be achieved through the elevated level of neurotrophic factors in penile tissue and subsequent neuroregenerative effects.

Surgical Anatomy of the Penis in Hypospadias: Magnetic Resonance Imaging Study of the Tissue Planes, Vessels, and Collaterals

To report the surgical anatomy of the penis in hypospadias with study of vessels in relation to fascial planes, glans, corpora cavernosa, and corpus spongiosum using magnetic resonance imaging. Twelve hypospadias presenting at older age (8-20 years) were studied with 1.5-T magnetic resonance imaging scanner and a 3-inch surface coil. Precontrast and postcontrast images were acquired using fast-spin echo sequences in sagittal, coronal, and transverse planes. The findings were processed in Volume Share 4.5, version Workstation, of General Electric Healthcare. Anatomic findings were verified during surgery. With imaging and surgical findings, a 3-dimensional conceptual diagram of surgical anatomy was created. Distinct layers of the skin, dartos fascia, Buck fascia, tunica albuginea, glans urothelium, lamina propria of glans, and corpus spongiosum were delineated with their spatial relationship. Axial pattern vessels of the dartos and its anastomosis with branches of dorsal penile vessels at the coronal sulcus, perforators along the corpus spongiosum, subglanular extension of the fascia, and intraglanular branches of the dorsal penile artery forming an arcade were visualized. Dorsomedial and dorsolateral axial pattern vessels are present in penile dartos with relative avascularity at dorsal midline in most cases. Subglanular extension of Buck fascia fused with the basal lamina propria of glans forms a barrier between the tip of corpora and the intraglanular arcade of vessels. Collaterals are present at coronal sulcus, along the bifurcated corpus spongiosum, and the dartos enabling blood flow between the terminal most branches of the external and internal pudendal vessels.

Immune cell gateways in the central nervous system regulated by regional neural stimulations

AbstractThe central nervous system (CNS) is an immune‐privileged tissue due to a specialized blood vessel structure, the blood–brain barrier. Indeed, the blood–brain barrier tightly limits cell migrations into the CNS. However, several immune cells, including T cells, can be found there. It is hypothesized that these cells have both beneficial and detrimental roles in immune surveillance and inflammation development, and that they can lead to multiple diseases, such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. The presence of immune cells within the CNS suggests a gateway that allows access from the peripheral blood stream. We recently identified dorsal vessels of the fifth lumbar spinal cord as a gateway for autoreactive T cells that opened with excessive chemokine expression. A chemokine inducer, the inflammation amplifier, which is hyperactivated by regional neural activations such as gravity, appears critical for formation of this fifth lumbar gateway. The gating of immune cells to the CNS can be artificially controlled by electric stimulations, at least in mice. We named this neural stimulation‐dependent gating the “gateway reflex.” Physical and/or chemical manipulations of the gateway reflex through the inflammation amplifier hold promising therapeutic value for neuroimmunological disorders.

Molecular evaluation of the phylogenetic position of the enigmatic species Trivettea papalotla (Bertsch) (Mollusca : Nudibranchia)

Tritoniid sea slugs are specialised predators that feed on a variety of octocorals, including soft corals, gorgonians and sea pens. Trivettea papalotla is a recently described species found in Baja California and mainland Mexico that is unusual in its morphology and feeding behaviour. It is the first tritoniid nudibranch known to feed on zoanthid anthozoans, specifically on an undescribed species of the genus Epizoanthus. Trivettea papalotla also has retractable respiratory structures, prominent dorsal vessels and several other traits not found in any other species of the Tritoniidae. In its original description these unique features of T. papalotla were considered autapomorphies, and the species was tentatively placed within Tritonia based on a morphological phylogenetic analysis. Subsequently, the monotypic genus Trivettea was erected for T. papalotla based on unpublished molecular data. In the present study, the phylogenetic placement of Trivettea is investigated based on molecular data. These phylogenies show T. papalotla is not nested within Tritonia or Tritoniidae and instead appears to be a basal, distinct cladobranch. However, the analyses conducted resulted in poorly resolved basal relationships, suggesting additional markers are probably necessary to fully resolve the phylogeny for the Cladobranchia.

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis.

Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of coronary vessels have been proposed, including the sinus venosus (SV), endocardium and proepicardium, but their relative contributions to the coronary circulation and the molecular mechanisms regulating their development are poorly understood. We created an ApjCreER mouse line as a lineage-tracing tool to map SV-derived vessels onto the heart and compared the resulting lineage pattern with endocardial and proepicardial contributions to the coronary circulation. The data showed a striking compartmentalization to coronary development. ApjCreER-traced vessels contributed to a large number of arteries, capillaries and veins on the dorsal and lateral sides of the heart. By contrast, untraced vessels predominated in the midline of the ventral aspect and ventricular septum, which are vessel populations primarily derived from the endocardium. The proepicardium gave rise to a smaller fraction of vessels spaced relatively uniformly throughout the ventricular walls. Dorsal (SV-derived) and ventral (endocardial-derived) coronary vessels developed in response to different growth signals. The absence of VEGFC, which is expressed in the epicardium, dramatically inhibited dorsal and lateral coronary growth but left vessels on the ventral side unaffected. We propose that complementary SV-derived and endocardial-derived migratory routes unite to form the coronary vasculature and that the former requires VEGFC, revealing its role as a tissue-specific mediator of blood endothelial development.