Neural Plexus Research Articles

The Pathologist's Role in the Diagnosis of Hirschsprung's Disease.

The possibilities, recent advances, and pitfalls in the histopathologic workup of specimens submitted for the diagnosis of Hirschsprung's disease (HSCR) are presented. A literature research was performed in the database PubMed including the years 2000 to 2024. The pathologist is involved in the diagnosis of HSCR in three scenarios: (1) the primary diagnosis in a child with the typical clinical symptoms, (2) the intra-operative guidance of surgery in a case where the diagnosis is already established, and (3) the confirmation of the diagnosis and the documentation of the extent of the disease in the resected specimen. Identification of ganglion cells in the enteric neural plexuses excludes HSCR, and the histological confirmation of a complete absence of these ganglion cells is the gold standard for its diagnosis. However, difficulties in the detection of ganglion cells with standard stains and/or a limited amount of tissue in the specimen submitted for diagnosis make supportive histologic stains and techniques, e.g., calretinin immunohistochemistry or acetylcholinesterase histochemistry necessary for an unequivocal diagnosis of HSCR. Improving the diagnostic accuracy of this life-threating disease is an interdisciplinary task. A good communication between pathologist and clinician, as well as mutual knowledge of skills and challenges of the other discipline, is necessary for a successful diagnostic teamwork.

Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease

We aimed to identify gut microbial features in Parkinson’s disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that species Akkermansia muciniphila was increased in PD, while species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also cause neuroinflammation in PD.

Enhancing surgical planning for abdominal tumors in children through advanced 3D visualization techniques: a systematic review of future prospects.

Preoperative three-dimensional (3D) reconstruction using sectional imaging is increasingly used in challenging pediatric cases to aid in surgical planning. Many case series have described various teams' experiences, discussing feasibility and realism, while emphasizing the technological potential for children. Nonetheless, general knowledge on this topic remains limited compared to the broader research landscape. The aim of this review was to explore the current devices and new opportunities provided by preoperative Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI). A systematic review was conducted to screen pediatric cases of abdominal and pelvic tumors with preoperative 3D reconstruction published between 2000 and 2023. Surgical planning was facilitated through virtual reconstruction or 3D printing. Virtual reconstruction of complex tumors enables precise delineation of solid masses, formulation of dissection plans, and suggests dedicated vessel ligation, optimizing tissue preservation. Vascular mapping is particularly relevant for liver surgery, large neuroblastoma with imaging-defined risk factors (IDRFs), and tumors encasing major vessels, such as complex median retroperitoneal malignant masses. 3D printing can facilitate specific tissue preservation, now accessible with minimally invasive procedures like partial nephrectomy. The latest advancements enable neural plexus reconstruction to guide surgical nerve sparing, for example, hypogastric nerve modelling, typically adjacent to large pelvic tumors. New insights will soon incorporate nerve plexus images into anatomical segmentation reconstructions, facilitated by non-irradiating imaging modalities like MRI. Although not yet published in pediatric surgical procedures, the next anticipated advancement is augmented reality, enhancing real-time intraoperative guidance: the surgeon will use a robotic console overlaying functional and anatomical data onto a magnified surgical field, enhancing robotic precision in confined spaces.

Vasoactive Intestinal Polypeptide in the Enteric Neural Plexus Promotes Microbiome Diversity and Resistance to GvHD

Abstract Graft-versus-host disease (GvHD) in allo-transplant recipients is characterized by donor T cell- mediated damage to recipient organs and changes in the gut microbiome. Vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, directs T cell responses towards a Th2 phenotype while inhibiting proinflammatory cytokine production. VIP-producing enteric neurons contribute to the mucosal barrier and maintain gut microbiome homeostasis. The impact of VIP production by host cells on GvHD remains unclear. We examined the effect of endogenous VIP synthesis in modulating GvHD in multiple murine allo-BMT models. VIP knock-out mice were exquisitely sensitive to GvHD, experiencing activation and expansion of Th1- and Th17-polarized T cells and early death. Transplanting radiation chimeric mice in which the VIP gene was knocked out in either hematopoietic or non-hematopoietic cells demonstrated that VIP production by non-hematopoietic tissues limited the GvHD activity of donor T cells. Immunofluorescence staining demonstrated VIP expression in enteric neurons in allo-BMT recipients, consistent with local effects of VIP on T cells and the gut microbiome. VIP- KO mice had lower gut pH, higher frequencies of Bacillota species, and less microbiome diversity post-transplantation. These data support the crucial role of VIP in maintaining the diversity of the gut microbiome with beneficial commensal species and in modulating the alloreactivity of donor T cells after allo-BMT.

Effects of Diabetes Mellitus on Corneal Immune Cell Activation and the Development of Keratopathy.

Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45+CD11b+Ly-6G- myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1β, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm2 in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK.

Subgemmal neurogenous plaque: a series of six cases and a literature overview.

The study aims to describe six subgemmal neurogenous plaque (SNP) cases and compile the previously available data on SNP. Searches on PubMed, Web of Science, Embase, Scopus, and a two-step study selection were performed to compile data from case reports/series of SNP published in English literature. Our six patients (range 29-63years) had SNP in the posterior lateral border of the tongue. Four of them were associated with lymphoepithelial cysts. A total of 15 studies, comprising 116 patients, were included in this overview. There was a slight predilection for female patients (56.0%) in the 5th (22.4%) and the 7th (23.9%) decades. The lateral border of the tongue (66.4%) was the most common anatomical location. The major manifestation was nodule/papule. Histologically, the presence of taste buds (n = 40/ 34.5%), superficial neural plexus (n = 32/ 27.6%), deep nerve fascicles (n = 32/ 27.6%), ganglion cells (n = 41/ 35.3%), and lymphoid tissue (n = 22/ 19.0%) was mainly reported. Surgical removal was the primary approach, with a low recurrence rate. Although largely unknown, SNP is a regular and likely frequent structure located in the tongue. The findings emphasize the importance of describing clinicopathological patterns of SNP as a differential diagnosis of neural lesions that affect the tongue.

Neuromuscular development in the emerging scyphozoan model system, Cassiopea xamachana: implications for the evolution of cnidarian nervous systems.

The scyphozoan Cassiopea xamachana is an emerging cnidarian model system for studying regeneration, animal-algae symbiotic relationships, and various aspects of evolutionary biology including the early emergence of animal nervous systems. Cassiopea has a life cycle similar to other scyphozoans, which includes the alternation between a sessile, asexual form (polyp) and a sexually reproducing stage, the medusa. The transition between the two forms is called strobilation, where the polyp releases a miniature medusa, the iconic ephyra, that subsequently develops into the adult medusa. In addition, Cassiopea polyps may reproduce asexually by budding off free-swimming so-called planuloid buds. While the development of planuloid buds and polyps has been studied in some detail, little is known about the ontogeny of the sexually produced planula larva. Using immunofluorescence labeling and confocal microscopy, we examined neuromuscular development during metamorphosis of the planula larva into the juvenile polyp in C. xamachana. For this purpose, we used tyrosinated α-tubulin-, FMRFamide- and serotonin-like immunoreactivity together with phalloidin labeling. Our results show a planula nervous system that consists of a basiectodermal neural plexus with mostly longitudinally oriented neurites. This neural meshwork is connected to sensory neurons in the superficial stratum of the ectoderm, which are exclusively localized in the aboral half of the larva. During settlement, this aborally concentrated nervous system of the planula is replaced completely by the orally concentrated nervous system of the polyp. Adult polyps show an extensive nerve net with a loose concentration around the oral disc. These findings are consistent with data from other scyphozoans and most likely constitute a conserved feature of scyphozoan discomedusae. Taken together, the data currently available suggest an aborally concentrated nervous system including sensory cells as part of the neural ground pattern of cnidarian planula larvae. The reorganization of the nervous system from anterior to posterior in planula-to-polyp metamorphosis most likely also constitutes an ancestral trait in cnidarian evolution.

A description of the bat star nervous system throughout larval ontogeny.

Larvae represent a distinct life history stage in which animal morphology and behavior contrast strongly to adult organisms. This life history stage is a ubiquitous aspect of animal life cycles, particularly in the marine environment. In many species, the structure and function of the nervous system differ significantly between metamorphosed juveniles and larvae. However, the distribution and diversity of neural cell types in larval nervous systems remains incompletely known. Here, the expression of neurotransmitter and neuropeptide synthesis and transport genes in the bat star Patiria miniata is examined throughout larval development. This characterization of nervous system structure reveals three main neural regions with distinct but overlapping territories. These regions include a densely innervated anterior region, an enteric neural plexus, and neurons associated with the ciliary band. In the ciliary band, cholinergic cells are pervasive while dopaminergic, noradrenergic, and GABAergic cells show regional differences in their localization patterns. Furthermore, the distribution of some neural subtypes changes throughout larval development, suggesting that changes in nervous system structure align with shifting ecological priorities during different larval stages, before the development of the adult nervous system. While past work has described aspects of P. miniata larval nervous system structure, largely focusing on early developmental timepoints, this work provides a comprehensive description of neural cell type localization throughout the extensive larval period.

Quantification of the intrinsic neural plexus of the heart – The missing link in histological tissue analysis

Background and objectiveThe heart is under strict regulation of the autonomic nervous system, during which, in a healthy state, the effects of sympathetic and parasympathetic branches are balanced. In recent years, there has been increasing interest in pathological remodeling and outgrowth of cardiac autonomic nerves in relation to arrhythmogenesis. However, the small size of the cardiac nerves in relatively large tissues renders research using histological quantification of these nerves extremely challenging and usually relies on quantification of the nerve density in selected regions of interest only. Our aim was to develop a method to be able to quantify the histological nerve density in transmural tissue sections. MethodsHere we describe a novel workflow that enables visualization and quantification of variable innervation types and their heterogeneity within transmural myocardial tissue sections. A custom semiautomatic workflow for the quantification of cardiac nerves involving Python, MATLAB and ImageJ is provided and described in this protocol in a stepwise and detailed manner. Representative resultsThe results of two example tissue sections are represented in this paper. An example tissue section taken from the infarction core with a high heterogeneity value of 0.20, 63.3% normal innervation, 12.2% hyperinnervation, 3.6% hypoinnervation and 21.0% denervation. The second example tissue section taken from an area of the left ventricle remote from the infarction showed a low heterogeneity value of 0.02, 95.3% normal innervation, 3.8% hyperinnervation, 0.5% hypoinnervation and 0.5% denervation. Conclusions: This approach has the potential to be broadly applied to any research involving high-resolution imaging of nerves in large tissues.

Cubital tunnel syndrome of the ulnar nerve caused by an epineural ganglion cyst: a case report and review of the literature

BackgroundThe ulnar nerve has a long and complex anatomical course, originating from the brachial neural plexus in the neck with nerve trunk formation at the posterior neck triangle, and on to the axilla. This intricate anatomical pathway renders the nerve susceptible to compression, direct injury, and traction throughout its course. Compression of the ulnar nerve is the second most common compression neuropathy of the median nerve adjacent to the wrist joint, after carpal tunnel syndrome.Case presentationA 45-year-old Sudanese housewife complained of progressive right forearm and hand muscle wasting, pain, and neuropathic symptoms. She was diagnosed with right-sided cubital tunnel syndrome. The diagnosis was derived intraoperatively from a nerve conduction study suggesting the level of conduction block and recommending decompression. Magnetic resonance imaging was not done preoperatively due to financial limitations. An epineural ganglion (15 × 20 mm2) compressing and flattening the ulnar nerve was diagnosed intraoperatively. Surgical decompression of the ulnar nerve and removal of the epineural ganglion achieved a remarkable postoperative result and pleasing outcome.ConclusionSurgical management is the cornerstone of treatment for compressive neuropathy and ranges from simple nerve decompression to complex neurolysis procedures and nerve transposition to adjust the anatomical course of the nerve.

Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension.

Persistent arterial hypertension initiates cardiac autonomic imbalance and alters cardiac tissues. Previous studies have shown that neural component contributes to arterial hypertension etiology, maintenance, and progression and leads to brain damage, peripheral neuropathy, and remodeling of intrinsic cardiac neural plexus. Recently, significant structural changes of the intracardiac neural plexus were demonstrated in young prehypertensive and adult hypertensive spontaneously hypertensive rats (SHR), yet structural alterations of intracardiac neural plexus that occur in the aged SHR remain undetermined. Thus, we analyzed the impact of uncontrolled arterial hypertension in old (48-52 weeks) SHR and the age-matched Wistar-Kyoto rats (WKY). Intrinsic cardiac neural plexus was examined using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in cardiac sections and whole-mount preparations. Our findings demonstrate that structural changes of intrinsic cardiac neural plexus caused by arterial hypertension are heterogeneous and may support recent physiological implications about cardiac denervation occurring together with the hyperinnervation of the SHR heart. We conclude that arterial hypertension leads to (i) the decrease of the neuronal body area, the thickness of atrial nerves, the number of myelinated nerve fibers, unmyelinated axon area and cumulative axon area in the nerve, and the density of myocardial nerve fibers, and (ii) the increase in myelinated nerve fiber area and density of neuronal bodies within epicardiac ganglia. Despite neuropathic alterations of myelinated fibers were exposed within intracardiac nerves of both groups, SHR and WKY, we consider that the determined significant changes in structure of intrinsic cardiac neural plexus were predisposed by arterial hypertension.

Examination of Abnormal Alpha-synuclein Aggregates in the Enteric Neural Plexus in Patients with Ulcerative Colitis.

Parkinson's disease (PD) is the second most neurodegenerative disease after Alzheimer's disease. Accumulating knowledge points to the notion that abnormal aggregation of alpha-synuclein (αSyn) starts in the gut and ascends to the substantia nigra via the vagus nerve in about a half of PD patients. Epidemiological studies revealed that ulcerative colitis (UC) increases a risk for PD 1.3 to 1.8-folds. However, it remains unknown whether αSyn is abnormally aggregated in the enteric neurons in UC patients. We first inspected and optimized the immunostaining protocols with an anti-phosphorylated αSyn antibody, pSyn#64, using the brain and the gut of eight autopsied cases (five with PD and three without PD). Then, we examined abnormal αSyn aggregation in the enteric neurons in 23 and 18 colectomized patients with and without UC, respectively. Five or more sections were stained for αSyn in each of 87 and 25 paraffin- embedded blocks in patients with and without UC, respectively. Ten different protocols of epitope exposure appropriately stained aggregated αSyn in the brain, but only complete lack of epitope exposure stained aggregated αSyn in the colon with low background. Abnormal αSyn aggregates, which was confirmed by co-localization of p62, in the enteric neurons were detected in a single patient with UC but not in any patients without UC. Omission of epitope exposure enabled us to immunostain aggregated αSyn in the colon by pSyn#64 with low nonspecific staining, but the number of 23 UC patients was not high enough to discern whether abnormal αSyn aggregation in the colonic neural plexus was increased in UC or not.

Ascendance of Abnormal α-synuclein Fibrils Through the Vagal Nerve in Parkinson's Disease

Parkinson's disease (PD) is caused by the abnormal accumulation of α-synuclein fibrils (Lewy bodies) in the substantia nigra. The α-synuclein fibrils behave like prions. Autopsy shows that α-synucleinopathy ascends from the brain stem to the substantia nigra. In patients with PD, the α-synuclein pathology is frequently observed in the intestinal neural plexus. In animal models, injection of α-synuclein fibrils in the gastric wall or the peritoneum caused immunostaining for aggregated α-synuclein fibrils in the substantia nigra. In Finland and Sweden, truncal vagotomy, but not partial vagotomy, reduced the chance of developing PD to 50% in 35 years. Of note, not all patients with PD show ascending α-synuclein pathology in the brain and that truncal vagotomy reduced the chance of developing PD to half. Thus, α-synucleinopathy is likely to start from the intestinal neural plexus and ascends through the vagal nerve to the substantia nigra in at least 50% of patients with PD. Additionally, short-chain fatty acids (SCFA)-producing intestinal bacteria are reduced in PD. Although the underlying mechanisms are currently under investigation, the vagal nerve also senses SCFA and transmits signals to the central nervous system. This pathway is likely to be compromised by gut dysbiosis in PD.

Subgemmal neurogenous plaque of posterolateral region in tongue: A case report and review of literature.

IntroductionThe subgemmal neurogenous plaque is a well-defined subepithelial neural plexus associated with taste buds, located within foliate, fungiform, and circumvallate papillae of the human tongue, that is poorly known by dentists and medical professionals. The hyperplasia of subgemmal neurogenous plaque may occur and it manifests as a papule, nodule, plaque, or ulcer in the lateral posterior border of the tongue inducing the overdiagnosis of reactive, cystic, or neoplastic lesions. The aims of this study are to report a case of a patient with subgemmal neurogenous plaque, and to provide a comprehensive review of other subgemmal neurogenous plaque in the posterolateral tongue with challenging diagnosis.Presentation of caseA 28-year-old female with a little yellowish nodule, asymptomatic, located in posterior left lateral border of the tongue. Accurate diagnosis was based in excisional biopsy and histopathological examination showing a superficial neurofibroma-like pattern, and a neuroma-like in the deep zone. The final diagnosis was subgemmal neurogenous plaque.DiscussionThe subgemmal neurogenous plaque has an erythematous nodule or papule in the border of the tongue that are frequently misdiagnosis as foliate papillitis and lymphoepithelial cyst. Despite the subgemmal neurogenous plaque be considered a normal structure, the biopsy is recommended for differential diagnosis with other benign or malignant lesions in tongue.ConclusionContributing with the dentists and medical professionals in their clinical practice, we reviewed the literature and added a case of subgemmal neurogenous plaque in the posterolateral region of the tongue, highlighting the importance of its recognition to avoid misdiagnosis.

Total colonic aganglionosis with ileum extension Hirschsprung's disease in an adult: A case report.

IntroductionHirschsprung's disease is a gastrointestinal anomaly affecting neuronal development and function. The primary abnormality is the absent ganglionic cells in the submucosal and myenteric neural plexuses. Disease presentation can vary, and patients may present with delayed meconium passage or late in adulthood. Total colonic aganglionosis is considered a rare subtype and even rarer to extend proximally into the small bowel. Therefore, adult Hirschsprung disease is frequently misdiagnosed as chronic constipation until comorbid events such as volvulus or perforation occur.Case presentationA 34 years South-Sudanese male presented with chronic constipation since early childhood, abdominal discomfort, pain, and distension. His bowel habits were infrequent, requiring occasional enemas. A strong family history of Hirschsprung disease was identified. He underwent total abdominal colectomy and end ileostomy. Postoperative diagnosis of TCA and small bowel extension of more than 50 cm was confirmed. The patient was discharged home after ileostomy education and possible future reconstruction.Clinical discussionHirschsprung's ileal extension resembles a risk of morbidities and mortality. It increases as the segment extends proximally. No international consensus on surgical management. It should be tailored to patient condition, diseased segment length, and the possible definitive primary reconstruction. Our patient's surgical diversion considered the patient's long-standing constipation history and dilated fecal-loaded ileum.ConclusionTCA requires a high index suspension during the workup of chronic constipation patients. There is no reported superior surgical approach, and it depends on the institution's experience and surgeon's expertise. Primary reconstruction can be achieved, but we recommend an ileostomy for such cases.

18F-FDG PET/CT and clinicopathological characteristics of neurolymphomatosis in lymphoma patients.

Neurolymphomatosis (NL) is a rare but serious manifestation defined as invasion of peripheral nervous system by malignant lymphocytes. Thus, this study investigated fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and clinicopathological characteristics of NL in lymphoma patients. Clinicopathological and 18F-FDG PET/CT findings and treatment regimens were retrospectively investigated in 20 lymphoma patients with NL, and analyzed their correlation with progression-free survival (PFS) and overall survival (OS). These 20 lymphoma patients (11 males, 9 females; median age, 49 years) included 10 primary and 10 secondary NL patients. Non-Hodgkin's lymphoma (NHL) was noted in 19 patients, B-cell NHL was associated with 18 cases, and diffuse large B-cell lymphoma was the most common. Notably, 18 patients were aggressive lymphoma while 2 were indolent lymphoma. The affected neural structures included nerve roots (n=17), peripheral nerves (n=3), cranial nerves (n=3), and neural plexus (n=2). Fluorine-18-FDG was avid in all cases, and the median maximum standardized uptake value (SUVmax) of neural and all lesions was 12.2 (range, 3.3-25.6) and 15.0 (range, 4.4-34.2), respectively. The median PFS and OS of all patients were 9.3 and 14.3 months. The 12-month OS rate of 18 patients with aggressive lymphoma receiving intrathecal chemotherapy/autologous stem cell transplants (IT chem/ASCT) was significantly higher than who did not (64.8% vs 15.9%). The majority of NL occurred in patients with aggressive lymphoma, of which B-cell NHL were the predominant subtypes. Fluorine-18-FDG PET/CT imaging of NL was mainly characterized by intense glucose accumulation alongside peripheral nerves, and IT chem/ASCT was suggested to improve the outcomes of NL.

Specializations of somatosensory innervation in the skin of humpback whales (Megaptera novaeangliae).

Cetacean behavior and life history imply a role for somatosensory detection of critical signals unique to their marine environment. As the sensory anatomy of cetacean glabrous skin has not been fully explored, skin biopsy samples of the flank skin of humpback whales were prepared for general histological and immunohistochemical (IHC) analyses of innervation in this study. Histology revealed an exceptionally thick epidermis interdigitated by numerous, closely spaced long, thin diameter penicillate dermal papillae (PDP). The dermis had a stratified organization including a deep neural plexus (DNP) stratum intermingled with small arteries that was the source of intermingled nerves and arterioles forming a more superficial subepidermal neural plexus (SNP) stratum. The patterns of nerves branching through the DNP and SNP that distribute extensive innervation to arteries and arterioles and to the upper dermis and PDP provide a dense innervation associated through the whole epidermis. Some NF-H+ fibers terminated at the base of the epidermis and as encapsulated endings in dermal papillae similar to Merkel innervation and encapsulated endings seen in terrestrial mammals. However, unlike in all mammalian species assessed to date, an unusual acellular gap was present between the perineural sheaths and the central core of axons in all the cutaneous nerves perhaps as mechanism to prevent high hydrostatic pressure from compressing and interfering with axonal conductance. Altogether the whale skin has an exceptionally dense low-threshold mechanosensory system innervation most likely adapted for sensing hydrodynamic stimuli, as well as nerves that can likely withstand high pressure experienced during deep dives.

Evaluation of Feasibility to Categorize Borderline Resectable Pancreatic Ductal Adenocarcinoma as T4 Tumor

Background: Resectability of pancreatic ductal adenocarcinoma (PDAC) is defined based on the tumor extension to major vessels regardless of tumor size (TS). Usually, however, only the tumor invasion to neural plexus but not to arterial wall is confirmed pathologically. In the current AJCC/UICC staging, PDAC contacting with celiac, hepatic, or superior mesenteric artery (BR-A) ≤180° by imaging studies is categorized into T4. We investigated whether classifying clinically assessed BR-A as T4 was feasible. Methods: Patients who underwent upfront pancreatectomy for resectable PDAC (R-PDAC) or BR-A were selected. TS of ≤2 cm, >2 cm and ≤4 cm, and >4 cm was defined as TSS, TSM, and TSL, respectively. In each group, the postoperative prognosis were compared according to TS. Results: Totally 264 patients were selected. In R-PDAC group, Overall survival (OS) of the patients with TSL (n =11) was significantly worse than those with TSS (n =62) (median, 11.9 vs. 36.7 months, P = 0.003) and TSM (n =150) (median, 11.9 vs. 35.9 months, P = 0.003). In BR-A group, there was no significant difference in OS among the three groups (median, TSS (n =7) vs. TSM (n =30) vs. TSL (n =4), 14.5 vs. 24.9 vs. 8.2 months, P = 0.194). OS of BR-A group (median, 22.9 months) was comparable for that of TSL in R-PDAC group P = 0.224). Conclusion: Clinically defined BR-A was associated with poor prognosis regardless of TS, but whether they should be categorized into T4 or T3 (TS >4 cm) remains to be elucidated.

Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen.

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.

A Case Report of a Rare Variation in the Lateral Cord of the Brachial Plexus

The brachial plexus is the largest and most complex neural plexus in the body located in the neck and axilla. So far, there have been many reports of various variations in the brachial plexus that are of clinical significance. In the present study, while dissecting the upper limb of a 54-year-old man in the dissection room of Shahid Sadoughi University of Medical Sciences in Yazd, a rare variation was observed in the lateral cord branches of the plexus. In this case, the medial pectoral nerve, which normally separates from the medial cord, originated from the lateral cord. Awareness of this variation is important for anatomists, surgeons, anesthesiologists and radiologists to interpret the graphs, etc., and can help to reduce clinical complications during surgery and better interpret and diagnose the graphs.