Differences between the glans and shaft of the penis: a review.

INTRODUCTION: The penis serves as a vital receptor in men, playing a significant role in sexual intercourse. While there are discernible disparities between the glans penis and the penile shaft, a comprehensive and detailed analysis of these distinctions is currently lacking. OBJECTIVES: This study aimed to review the existing literature on the variances between the glans penis and the penile shaft, providing a systematic examination of their anatomical and histological dissimilarities. METHODS: Our investigation encompassed a thorough search of the published literature, including original articles, reviews, letters to the editor, and case reports focused on the penis. We conducted a comprehensive review of the anatomical and histological dissimilarities between the glans penis and the penile shaft. RESULTS: The following key differences were identified. First, regarding innervation, the glans penis and the penile shaft possess distinct neural pathways. The glans penis exhibits a 3-dimensional structure, while the penile shaft exhibits a 2-dimensional distribution. Notably, the nerves of the penile shaft extend penetrating branches into the corpus cavernosum. Furthermore, there are variations in nerve-specific antibodies between the 2 regions. Second, regarding composition, the glans penis and the penile shaft consist of dissimilar cavernous bodies. The glans penis contains unique epithelial structures and receptors, setting it apart from the penile shaft. Third, regarding the veins, there are disparities in the venous systems of the glans penis and the penile shaft. Fourth, regarding biothesiometry, variances in biothesiometry research have been observed between the 2 regions. CONCLUSION: There are differences between the glans and the shaft. To further advance our understanding, future research should delve deeper into the discrepancies between the glans penis and the penile shaft. Additionally, a more specialized subdivision of the glans penis and the penile shaft would facilitate more precise and tailored treatments.

The anatomy, neurophysiology, and cellular mechanisms of intradental sensation.

Somatosensory innervation of the oral cavity enables the detection of a range of environmental stimuli including minute and noxious mechanical forces. The trigeminal sensory neurons underlie sensation originating from the tooth. Prior work has provided important physiological and molecular characterization of dental pulp sensory innervation. Clinical dental experiences have informed our conception of the consequence of activating these neurons. However, the biological role of sensory innervation within the tooth is yet to be defined. Recent transcriptomic data, combined with mouse genetic tools, have the capacity to provide important cell-type resolution for the physiological and behavioral function of pulp-innervating sensory neurons. Importantly, these tools can be applied to determine the neuronal origin of acute dental pain that coincides with tooth damage as well as pain stemming from tissue inflammation (i.e., pulpitis) toward developing treatment strategies aimed at relieving these distinct forms of pain.

Expression of semaphorin-3A in the joint and role in osteoarthritis.

Osteoarthritis (OA) is characterised by the deterioration of cartilage in the joints and pain. We hypothesise that semaphorin-3A (sema-3A), a chemorepellent for sensory nerves, plays a role in joint degradation and pain. We used the mechanical joint loading (MJL) model of OA to investigate sema-3A expression in the joint and examine its association with the development of OA and pain. We also analyse its effect on chondrocyte differentiation using the ATDC5 cell line. We demonstrate that sema-3A is present in most tissues in the healthy joint and its expression increases in highly innervated tissues, such as cruciate ligaments, synovial lining and subchondral bone, in loaded compared to nonloaded control joints. In contrast, sema-3A expression in cartilage was decreased in the severe OA induced by the application of high loads. There was a significant increase in circulating sema-3A, 6 weeks after MJL compared to the nonloaded mice. mRNA for sema-3A and its receptor Plexin A1 were upregulated in the dorsal root ganglia of mice submitted to MJL. These increases were supressed by zoledronate, an inhibitor of bone pain. Sema-3A was expressed at all stages of Chondrocyte maturation and, when added exogenously, stimulated expression of markers of chondrocyte differentiation. This indicates that sema-3A could affect joint tissues distinctively during the development of OA. In highly innervated joint tissues, sema-3A could control innervation and/or induce pain-associated neuronal changes. In cartilage, sema-3A could favour its degeneration by modifying chondrocyte differentiation.

Innervation patterns of hamstring muscles, including morphological descriptions and clinical implication.

PURPOSE: The hamstrings muscles are innervated by sciatic nerve branches. However, previous studies assessing which and how many branches innervate each muscle have yielded discrepant results. This study investigated the innervation patterns of hamstrings. MATERIALS AND METHODS: Thirty-five cadaver limbs were investigated. The average age of subjects was 78.6 ± 17.2 years, with 48.6% male and 51.4% female, while 57.1% were right limbs and 42.9% left. The sciatic nerve, hamstrings and associated structures were dissected. The number of nerve branches for each muscle and the level where they penetrated the muscle were recorded. RESULTS: The sciatic nerve was connected by a fibrous band to the long head of the biceps femoris. This muscle was innervated by either one or two branches, which penetrated the muscle into its superior or middle third. The short head of the biceps femoris was innervated by a single nerve that usually penetrated its middle third, but sometimes inferiorly or, less commonly, superiorly. The semitendinosus was always innervated by two branches, the superior branch penetrating its upper third, the inferior mostly the middle third. The semimembranosus usually was innervated by a single nerve branch that penetrated the muscle at its middle or lower third. Four specimens revealed common nerves that innervated than one muscle. CONCLUSIONS: We have characterized hamstring innervation patterns, knowledge that is relevant to neurolysis, surgery of the thigh, and other procedures. Moreover, a mechanical connection between the sciatic nerve and biceps femoris long head was identified that could explain certain neuralgias.

Contralateral Facial Innervation in Healthy Subjects and in Patients with Peripheral Facial Palsy.

Background: We aimed to investigate the extent of the response of the orbicularis oris muscle to stimulation of the contralateral facial nerve both in patients with peripheral facial palsy (PFP) and in healthy subjects. Methods: EMG was performed at 2-6 weeks after the onset of PFP in the patient group and at any time in the healthy control group. We performed nerve conduction testing, electroneurography, and surface and needle EMG. Results: A total of 276 participants (patients/healthy controls: 218/58) were analyzed. The extent of the response of the contralateral orbicularis oris muscles to facial nerve stimulation was higher in healthy controls compared to that in the affected group. The response of the contralateral orbicularis oris muscles to stimulation of the paralyzed facial nerve was more extensive in those patients to whom glucocorticoid or physical therapy had been given. Cross-facial innervation in the orbicularis oris muscle extended up to 1.5 cm in one-third of healthy controls and was higher than that in those with PFP. Glucocorticoid or physical therapy seemed to improve cross-innervation in facial palsy. Conclusions: Our findings suggest that the stimulus leading to the contralateral muscular response is mediated through crossing axons rather than muscular fibers.

Localization of sensory nerve terminals containing calcitonin gene-related peptide (CGRP) on striated muscle fibers in the rat esophagus: Evidence for triple innervation via motor endplates.

BACKGROUND: Many esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on a few striated muscle fibers in the rat esophagus, implying that these muscle fibers are triply innervated. In this study, we examined the localization and origin of CGRP-nerve endings in striated muscles to consider their possible roles in the esophagus regarding triple innervation. METHODS: Wholemounts of the rat esophagus were immunolabeled to detect CGRP-nerve endings in striated muscles. Also, retrograde tracing was performed by injecting Fast Blue (FB) into the esophagus, and cryostat sections of the medulla oblongata, nodose ganglion (NG), and the tenth thoracic (T10) dorsal root ganglion (DRG) were immunostained to identify the origin of the CGRP-nerve endings. RESULTS: CGRP-fine, varicose nerve endings were localized in motor endplates on a few esophageal striated muscle fibers (4 %), most of which received nitric oxide (NO) synthase nerve terminals, and most of the CGRP nerve endings were SP- and transient receptor potential vanilloid member 1 (TRPV1)-positive. Retrograde tracing showed many FB-labeled CGRP-neurons positive for SP and TRPV1 in the NG and T10 DGR. CONCLUSIONS: This study suggests that the CGRP-varicose nerve endings containing SP and TRPV1 in motor endplates are sensory, and a few esophageal striated muscle fibers are triply innervated. The nerve endings may detect acetylcholine-derived acetic acid from the vagal motor nerve endings and NO from esophageal intrinsic nerve terminals in the motor endplates to regulate esophageal motility.

Advanced Insights into Human Uterine Innervation: Implications for Endometriosis and Pelvic Pain.

(1) Background: Understanding uterine innervation, an essential aspect of female reproductive biology, has often been overlooked. Nevertheless, the complex architecture of uterine innervation plays a significant role in conditions such as endometriosis. Recently, advances in histological techniques have provided unprecedented details about uterine innervation, highlighting its intricate structure, distribution, and density. The intricate nature of uterine innervation and its influence on pathologies such as endometriosis has garnered increasing attention. (2) Objectives: This review aims to compile, analyze, and summarize the existing research on uterine innervation, and investigate its implications for the pathogenesis of endometriosis and associated pain. (3) Methods: A systematic review was conducted in line with PRISMA guidelines. Using the PubMed database, we searched relevant keywords such as "uterine innervation", "endometriosis", and "pain association". (4) Results: The initial literature search yielded a total of 3300 potential studies. Of these, 45 studies met our inclusion criteria and were included in the final review. The analyzed studies consistently demonstrated that the majority of studies focused on macroscopic dissection of uterine innervation for surgical purposes. Fewer studies focused on micro-innervation for uterine innervation. For endometriosis, few studies focused on neural pain pathways whereas many studies underlined an increase in nerve fiber density within ectopic endometrial tissue. This heightened innervation is suggested as a key contributor to the chronic pain experienced by endometriosis patients. (5) Conclusions: The understanding of uterine innervation, and its alterations in endometriosis, offer promising avenues for research and potential treatment.

Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.

Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.

Schwann cells in the normal and pathological lung microenvironment.

The lungs are a key organ in the respiratory system. They are regulated by a complex network of nerves that control their development, structure, function, and response to various pathological stimuli. Accumulating evidence suggests the involvement of a neural mechanism in different pathophysiological conditions in the lungs and the development and progression of common respiratory diseases. Lung diseases are the chief source of death globally. For instance, lung cancer is the second most commonly diagnosed malignancy, after prostate cancer in men and breast cancer in women, and is the most lethal cancer worldwide. However, although airway nerves are accepted as a mechanistically and therapeutically important feature that demands appropriate emphasizing in the context of many respiratory diseases, significantly less is known about the role of the neuroglial cells in lung physiology and pathophysiology, including lung cancer. New data have uncovered some cellular and molecular mechanisms of how Schwann cells, as fundamental components of the peripheral nervous system, may regulate lung cancer cells' survival, spreading, and invasiveness in vitro and in vivo. Schwann cells control the formation and maintenance of the lung cancer microenvironment and support metastasis formation. It was also reported that the number of lung cancer-associated Schwann cells correlates with patients' survival. Different factors secreted by Schwann cells, including microRNA, are known to sharpen the lung cancer environment by regulating the tumor-neuro-immune axis. Further clinical and experimental studies are required to elucidate the detailed role of Schwann cells in creating and maintaining pulmonary tumor-neuro-immune axis, which will advance our understanding of the pathogenesis of lung cancer and may inform therapeutic hypotheses aiming neoplasms and metastases in the lung.

An Elastin-derived composite matrix for enhanced vascularized and innervated bone tissue reconstruction: from material development to preclinical evaluation.

Despite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, we developed a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin-like polypeptides (ELPs) grafted with laminin-derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation led to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, we performed longitudinal micro-CT analysis, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP-based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP-based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration. This article is protected by copyright. All rights reserved.

The relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments - A minireview.

The acceptance of the tumor as a non-isolated structure within the organism has opened a space for the study of a wide spectrum of potential direct and indirect interactions, not only between the tumor tissue and its vicinity, but also between the tumor and its macroenvironment, including the nervous system. Although several lines of evidence have implicated the nervous system in tumor growth and progression, for many years, researchers believed that tumors lacked innervation and the notion of indirect neuro-neoplastic interactions via other systems (e.g., immune, or endocrine) predominated. The original idea that tumors are supplied not only by blood and lymphatic vessels, but also autonomic and sensory nerves that may influence cancer progression, is not a recent phenomenon. Although in the past, mainly due to the insufficiently sensitive methodological approaches, opinions regarding the presence of nerves in tumors were inconsistent. However, data from the last decade have shown that tumors are able to stimulate the formation of their own innervation by processes called neo-neurogenesis and neo-axonogenesis. It has also been shown that tumor infiltrating nerves are not a passive, but active components of the tumor microenvironment and their presence in the tumor tissue is associated with an aggressive tumor phenotype and correlates with poor prognosis. The aim of the present review was to 1) summarize the available knowledge regarding the course of tumor innervation, 2) present the potential mechanisms and pathways for the possible induction of new nerve fibers into the tumor microenvironment, and 3) highlight the functional significance/consequences of the nerves infiltrating the tumors.

Effects of Aging and Nerve Growth Factor on Neuropeptide Expression and Cholinergic Innervation of the Rat Basolateral Amygdala.

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.

HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice.

Browning of white adipose tissue (WAT) is a focus of research in type 2 diabetes mellitus (T2DM) and metabolism, which may be a potential molecular mechanism for high-intensity interval training (HIIT) to improve T2DM. In this study, male C57BL/6J wild-type mice were subjected to an 8-week HIIT regimen following T2DM induction through a high-fat diet (HFD) combined with streptozotocin (STZ) injection. We found that HIIT improved glucose metabolism, body weight, and fat mass in T2DM mice. HIIT also decreased adipocyte size and induced browning of WAT. Our data revealed a decrease in TNFα and an increase in IL-10 with HIIT, although the expression of chemokines MCP-1 and CXCL14 was increased. We observed increased pan-macrophage infiltration induced by HIIT, along with a simultaneous decrease in the expression of M1 macrophage markers (iNOS and CD11c) and an increase in M2 macrophage markers (Arg1 and CD206), suggesting that HIIT promotes M2 macrophage polarization. Additionally, HIIT upregulated the expression of Slit3 and neurotrophic factors (BDNF and NGF). The expression of the sympathetic marker tyrosine hydroxylase (TH) and the nerve growth marker GAP43 was also increased, demonstrating the promotion of sympathetic nerve growth and density by HIIT. Notably, we observed macrophages co-localizing with TH, and HIIT induced the accumulation of M2 macrophages around sympathetic nerves, suggesting a potential association between M2 macrophages and increased density of sympathetic nerves. In conclusion, HIIT induces adipose tissue browning and improves glucose metabolism in T2DM mice by enhancing M2 macrophage polarization and promoting sympathetic nerve growth and density.

Discontinuity third harmonic generation microscopy for label-free imaging and quantification of intraepidermal nerve fibers.

Label-free imaging methodologies for nerve fibers rely on spatial signal continuity to identify fibers and fail to image free intraepidermal nerve endings (FINEs). Here, we present an imaging methodology-called discontinuity third harmonic generation (THG) microscopy (dTHGM)-that detects three-dimensional discontinuities in THG signals as the contrast. We describe the mechanism and design of dTHGM and apply it to reveal the bead-string characteristics of unmyelinated FINEs. We confirmed the label-free capability of dTHGM through a comparison study with the PGP9.5 immunohistochemical staining slides and a longitudinal spared nerve injury study. An intraepidermal nerve fiber (IENF) index based on a discontinuous-dot-connecting algorithm was developed to facilitate clinical applications of dTHGM. A preliminary clinical study confirmed that the IENF index was highly correlated with skin-biopsy-based IENF density (Pearson's correlation coefficient R = 0.98) and could achieve differential identification of small-fiber neuropathy (p = 0.0102) in patients with diabetic peripheral neuropathy.

Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.

The kidney functions as a finely tuned sensor to balance body fluid composition and filter out waste through complex coordinated mechanisms. This versatility requires tight neural control, with innervating efferent nerves playing a crucial role in regulating blood flow, glomerular filtration rate, water and sodium reabsorption, and renin release. In turn sensory afferents provide feedback to the central nervous system for the modulation of cardiovascular function. However, the cells targeted by sensory afferents and the physiological sensing mechanisms remain poorly characterized. Moreover, how the kidney is innervated during development to establish these functions remains elusive. Here, we utilized a combination of light-sheet and confocal microscopy to generate anatomical maps of kidney sensory and sympathetic nerves throughout development and resolve the establishment of functional crosstalk. Our analyses revealed that kidney innervation initiates at embryonic day (E)13.5 as the nerves associate with vascular smooth muscle cells and follow arterial differentiation. By E17.5 axonal projections associate with kidney structures such as glomeruli and tubules and the network continues to expand postnatally. These nerves are synapsin I-positive, highlighting ongoing axonogenesis and the potential for functional crosstalk. We show that sensory and sympathetic nerves innervate the kidney concomitantly and classify the sensory fibers as calcitonin gene related peptide (CGRP)+, substance P+, TRPV1+, and PIEZO2+, establishing the presence of PIEZO2 mechanosensory fibers in the kidney. Using retrograde tracing, we identified the primary dorsal root ganglia, T10-L2, from which PIEZO2+ sensory afferents project to the kidney. Taken together our findings elucidate the temporality of kidney innervation and resolve the identity of kidney sympathetic and sensory nerves.

Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice.

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aß fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.

The structure and function of the human choroid.

In this manuscript, the structure of the human choroid is reviewed with emphasis of the macro- and microscopic anatomy including Bruch's membrane, choriocapillaris, Sattler's and Haller's layer, and the suprachoroid. We here discuss the development of the choroid, as well as the question of choroidal lymphatics, and further the neuronal control of this tissue, as well as the pathologic angiogenesis. Wherever possible, functional aspects of the various structures are included and reviewed.

Emerging roles of nerve-bone axis in modulating skeletal system.

Over the past decades, emerging evidence in the literature has demonstrated that the innervation of bone is a crucial modulator for skeletal physiology and pathophysiology. The nerve-bone axis sparked extensive preclinical and clinical investigations aimed at elucidating the contribution of nerve-bone crosstalks to skeleton metabolism, homeostasis, and injury repair through the perspective of skeletal neurobiology. To date, peripheral nerves have been widely reported to mediate bone growth and development and fracture healing via the secretion of neurotransmitters, neuropeptides, axon guidance factors, and neurotrophins. Relevant studies have further identified several critical neural pathways that stimulate profound alterations in bone cell biology, revealing a complex interplay between the skeleton and nerve systems. In addition, inspired by nerve-bone crosstalk, novel drug delivery systems and bioactive materials have been developed to emulate and facilitate the process of natural bone repair through neuromodulation, eventually boosting osteogenesis for ideal skeletal tissue regeneration. Overall, this work aims to review the novel research findings that contribute to deepening the current understanding of the nerve-bone axis, bringing forth some schemas that can be translated into the clinical scenario to highlight the critical roles of neuromodulation in the skeletal system.

The relevance of the superior cervical ganglion for cardiac autonomic innervation in health and disease: a systematic review.

PURPOSE: The heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior cervical ganglia (SCG) is used in many experimental studies. The clinical relevance of the SCG to cardiac innervation is controversial. We investigated current morphological and functional evidence as well as controversies on the contribution of the SCG to cardiac innervation. METHODS: A systematic literature review was conducted in PubMed, Embase, Web of Science, and COCHRANE Library. Included studies received a full/text review and quality appraisal. RESULTS: Seventy-six eligible studies performed between 1976 and 2023 were identified. In all species studied, morphological evidence of direct or indirect SCG contribution to cardiac innervation was found, but its contribution was limited. Morphologically, SCG sidedness may be relevant. There is indirect functional evidence that the SCG contributes to cardiac innervation as shown by its involvement in sympathetic overdrive reactions in cardiac disease states. A direct functional contribution was not found. Functional data on SCG sidedness was largely unavailable. Information about sex differences and pre- and postnatal differences was lacking. CONCLUSION: Current literature mainly supports an indirect involvement of the SCG in cardiac innervation, via other structures and plexuses or via sympathetic overdrive in response to cardiac diseases. Morphological evidence of a direct involvement was found, but its contribution seems limited. The relevance of SCG sidedness, sex, and developmental stage in health and disease remains unclear and warrants further exploration.

Schwann cells in pancreatic cancer: Unraveling their multifaceted roles in tumorigenesis and neural interactions.

Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.