Ganglion Size Research Articles

Elp1 function in placode-derived neurons is critical for proper trigeminal ganglion development.

The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure. We performed RNA sequencing on the forming chick trigeminal ganglion and identified Elongator acetyltransferase complex subunit 1 (Elp1) for further study. Mutations in ELP1 cause familial dysautonomia (FD), a fatal disorder characterized by the presence of smaller trigeminal nerves and sensory deficits. While Elp1 has established roles in neurogenesis, its function in placode cells during trigeminal gangliogenesis has not been investigated. To this end, we used morpholinos to deplete Elp1 from chick trigeminal placode cells. Elp1 knockdown decreased trigeminal ganglion size and led to aberrant innervation of the eye by placode-derived neurons. Trigeminal nerve branches also appeared to exhibit reduced axon outgrowth to target tissues. These findings reveal a new role for Elp1 in placode-derived neurons during chick trigeminal ganglion development. These results have potential high significance to provide new insights into trigeminal ganglion development and the etiology of FD.

Fluorescence visualization dynamics of carbonated water injection processes in homogeneous glass micromodels

Understanding the flow behavior of oil–water phases in porous media is crucial for revealing the kinetic mechanisms underlying oil–water movement. In this study, we designed and constructed a fluorescence visualization experimental platform for carbonated water injection (CWI). We evaluated the effects of nine distinct injection rates on oil production and CO2 sequestration capabilities using three types of homogeneous porous structure micromodels. The microscale oil–water seepage behavior at the pore scale was also explored. The experimental results indicate that optimally increasing the injection rate can improve displacement efficiency, whereas excessively high rates may lead to viscous and capillary fingering. The geometry of the micromodels, particularly the hexagonal matrix, demonstrates potential advantages in enhancing oil displacement due to its uniform flow paths. The capillary number (Ca) significantly influences oil droplet capture behavior within micromodels. For instance, micromodel A captures the largest ganglion area at low Ca values, with a noticeable reduction in average ganglion area as Ca increases. Conversely, micromodels B and C exhibit similar trends in ganglion size variation at high Ca values, suggesting a more uniform impact of pore structure on oil droplet capture behavior. At elevated Ca values, capillary forces exert a more uniform and controlled effect on oil droplet capture and release, minimizing size variability. Additionally, the injection rate plays a critical role in CO2 sequestration, with higher rates promoting convective mixing between CO2 and reservoir fluids, thereby enhancing dissolution and storage efficiency. The complexity of the pore structure, characterized by the presence of micropores and macropores, affects the dissolution kinetics and mobility of CO2, influencing sequestration efficiency. These experimental findings provide valuable insights into the dynamics of oil–water motion and the potential for enhanced oil recovery (EOR) and CO2 storage, offering essential guidance for optimizing CWI strategies in the petroleum industry.

N-cadherin facilitates trigeminal sensory neuron outgrowth and target tissue innervation.

During embryonic development, diverse cell types coordinate to form functionally complex tissues. Exemplifying this process, the trigeminal ganglion emerges from the condensation of two distinct precursor cell populations, cranial placodes and neural crest, with neuronal differentiation of the former preceding the latter. While its dual cellular origin has been understood for decades, the molecules orchestrating trigeminal ganglion formation remain relatively obscure. Initial assembly of the trigeminal ganglion is mediated by cell adhesion molecules, including neural cadherin (N-cadherin), which is first expressed by placodal neurons and is required for their proper condensation with other neurons and neural crest cells. Axon outgrowth first occurs from placodal neurons, but as gangliogenesis proceeds, neural crest cells also differentiate into N-cadherin-expressing neurons, and together both extend axons toward target tissues. However, a role for N-cadherin in regulating axon outgrowth and innervation of target tissues by trigeminal neurons has not been explored. To this end, we depleted N-cadherin from chick trigeminal placode cells and observed decreases in trigeminal ganglion size, nerve growth, and target innervation in vivo, phenotypes that could only partially be attributed to increased apoptosis early in gangliogenesis. Accordingly, neurite number and branching of neural crest-derived neurons was decreased in vitro in response to N-cadherin knockdown in placode cells, providing a novel non-cell autonomous explanation for these morphological changes. Inhibiting N-cadherin-mediated adhesion with a function-blocking antibody prevented axon extension in most, but not all, placode-derived trigeminal neurons in vitro, indicating potential unique requirements for N-cadherin in various neuronal subtypes. Collectively, these findings reveal persistent cell autonomous and non-cell autonomous functions for N-cadherin, thus highlighting the critical role of N-cadherin in mediating reciprocal interactions between neural crest and placode neuronal derivatives during trigeminal ganglion development.

MiR-203 secreted in extracellular vesicles mediates the communication between neural crest and placode cells required for trigeminal ganglia formation.

While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, by using chick embryos, we show that the microRNA (miR)-203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. By employing cell-specific electroporations for either miR-203 sponging or genomic editing using CRISPR/Cas9, we elucidated that neural crest cells serve as the source, while placode cells serve as the site of action for miR-203 in trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses an miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.

Elp1 function in placode-derived neurons is critical for proper trigeminal ganglion development.

The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure. We performed RNAsequencing on the forming chick trigeminal ganglion and identified Elongator acetyltransferase complex subunit 1 ( Elp1 ) for further study. Mutations in ELP1 cause familial dysautonomia (FD), a fatal disorder characterized by the presence of smaller trigeminal nerves and sensory deficits. While Elp1 has established roles in neurogenesis, its functions in placode cells during trigeminal gangliogenesis have not been investigated. To this end, we used morpholinos to deplete Elp1 from chick trigeminal placode cells. Elp1 knockdown decreased trigeminal ganglion size and led to aberrant innervation of the eye by placode-derived neurons. Trigeminal nerve branches exhibited fewer axons, and abnormal interactions between placode-derived neurons and neural crest cells were observed. These findings reveal a new role for Elp1 in chick placode-derived neurons during trigeminal ganglion development. These results have potential high significance to provide new insights into trigeminal ganglion development and the etiology of FD. Elp1 is expressed in undifferentiated neural crest cells and placode-derived neurons contributing to the trigeminal ganglion.Elp1 knockdown in trigeminal placode cells reduces trigeminal ganglion size.Elp1 depletion from trigeminal placode cells leads to aberrant target tissue innervation and disrupts proper neural crest-placodal neuron interactions in the trigeminal ganglion. NIH R01DE024217 and NIH R03HD108480.

Stroke Alters the Function of Enteric Neurons to Impair Smooth Muscle Relaxation and Dysregulates Gut Transit.

Gut dysmotility is common after ischemic stroke, but the mechanism underlying this response is unknown. Under homeostasis, gut motility is regulated by the neurons of the enteric nervous system that control contractile/relaxation activity of muscle cells in the gut wall. More recently, studies of gut inflammation revealed interactions of macrophages with enteric neurons are also involved in modulating gut motility. However, whether poststroke gut dysmotility is mediated by direct signaling to the enteric nervous system or indirectly via inflammatory macrophages is unknown. We examined these hypotheses by using a clinically relevant permanent intraluminal midcerebral artery occlusion experimental model of stroke. At 24 hours after stroke, we performed invivo and exvivo gut motility assays, flow cytometry, immunofluorescence, and transcriptomic analysis. Stroke-induced gut dysmotility was associated with recruitment of muscularis macrophages into the gastrointestinal tract and redistribution of muscularis macrophages away from myenteric ganglia. The permanent intraluminal midcerebral artery occlusion model caused changes in gene expression in muscularis macrophages consistent with an altered phenotype. While the size of myenteric ganglia after stroke was not altered, myenteric neurons from post-permanent intraluminal midcerebral artery occlusion mice showed a reduction in neuronal nitric oxide synthase expression, and this response was associated with enhanced intestinal smooth muscle contraction exvivo. Finally, chemical sympathectomy with 6-hydroxydopamine prevented the loss of myenteric neuronal nitric oxide synthase expression and stroke-induced slowed gut transit. Our findings demonstrate that activation of the sympathetic nervous system after stroke is associated with reduced neuronal nitric oxide synthase expression in myenteric neurons, resulting in impaired smooth muscle relaxation and dysregulation of gut transit.

Steady-State Dynamics of Ganglia Populations During Immiscible Two-Phase Flows in Porous Micromodels: Effects of the Capillary Number and Flow Ratio on Effective Rheology and Size Distributions

We study experimentally the flow of non-wetting ganglia during the co-injection of n-heptane and water in a predominantly 2D PMMA micromodel, which is constructed based on a stochastic digital algorithm. The dynamics of the phase distribution patterns are recorded optically and post-processed using cluster identification and motion tracking algorithms in order to study the characteristics and the interactions between the mobile and stranded ganglia populations. We focus primarily on the effects of the capillary number (Ca) and the ratio of the injection flow rates (Q) on the observed ganglia size distributions and the effective two-phase rheology. Our experimental setup allows for the study of ganglia fragmentation and coalescence dynamics over five orders of magnitude (in terms ganglia sizes), thus offering novel physical insight on the pore-scale characteristics of different ganglia populations and on how their interactions determine the relative permeability of the non-wetting phase. We demonstrate that the rates of ganglia fragmentation and coalescence intensify at higher Ca values, as viscous forces become dominant over capillary ones, leading to a log-normal size distribution that shifts toward smaller mean values. This effect is directly correlated with the emergence of new flow paths that develop progressively through narrower pores-throats, where the continuous wetting phase sweeps ganglia with sizes smaller than the mean pore-throat diameter. These flow paths further contribute to the Darcy scale velocity of the non-wetting phase, thus leading to a power-law Darcian regime at intermediate Ca values with a scaling exponent that is found to be a function of Q.

Identification and prevalence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi from the dog population in Wrocław, Poland

In recent years, there has been growing interest in exploring the potential health benefits of incorporating natural plant substances into the diets of farm animals. Basket willow (Salix viminalis), rich in flavonoids, tannins, and salicylates, has emerged as a candidate with analgesic, anti-inflammatory, and anthelmintic properties, making it appealing for integration into ruminant farming practices. This study aimed to analyze the effects of dietary supplementation with basket willow on the neuroanatomical properties of the small intestine in farmed fallow deer. Immunohistochemical methods and morphometric measurements were employed to assess changes in noradrenergic, galaninergic and nitrergic innervation patterns. Twenty-four fallow deer were divided randomly, with 12 individuals placed in both a control group and an experimental group, with the latter receiving willow supplementation. The results revealed significant alterations in the morphology and innervation patterns of the enteric nervous system (ENS) in the experimental group, including a decrease in ganglion size and nitric oxide synthase (NOS) immunoreactive nerve fibers, and an increase in galanin immunoreactive neurons. These findings suggest a potential modulation of gastrointestinal function by willow supplementation. However, caution is warranted due to the high salicylate content in basket willow, which may pose risks to gastrointestinal integrity. Overall, while basket willow supplementation shows promise in enhancing animal farming methods, further research is needed to elucidate its mechanisms and optimize its use in ruminant farming practices.

High Prevalence of Collagenopathies in Preterm- and Term-Born Children With Periventricular Venous Hemorrhagic Infarction.

The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction in preterm neonates. Genetic analysis and magnetic resonance imaging were performed in 85 children: term-born children (≥36 gestational weeks) with antenatal periventricular hemorrhagic infarction (n = 6) or presumed antenatal (n = 40) periventricular venous infarction and preterm children (<36 gestational weeks) with periventricular hemorrhagic infarction (n = 39). Genetic testing was performed using exome or large gene panel (n = 6700 genes) sequencing. Pathogenic variants associated with stroke were found in 11 of 85 (12.9%) children with periventricular hemorrhagic infarction/periventricular venous infarction. Among the pathogenic variants, COL4A1/A2 and COL5A1 variants were found in 7 of 11 (63%) children. Additionally, 2 children had pathogenic variants associated with coagulopathy, whereas 2 other children had other variants associated with stroke. Children with collagenopathies had significantly more often bilateral multifocal stroke with severe white matter loss and diffuse hyperintensities in the white matter, moderate to severe hydrocephalus, moderate to severe decrease in size of the ipsilesional basal ganglia and thalamus compared to children with periventricular hemorrhagic infarction/periventricular venous infarction without genetic changes in the studied genes (P ≤ .01). Severe motor deficit and epilepsy developed more often in children with collagenopathies compared to children without genetic variants (P = .0013, odds ratio [OR] = 233, 95% confidence interval [CI]: 2.8-531; and P = .025, OR = 7.3, 95% CI: 1.3-41, respectively). Children with periventricular hemorrhagic infarction/periventricular venous infarction have high prevalence of pathogenic variants in collagene genes (COL4A1/A2 and COL5A1). Genetic testing should be considered for all children with periventricular hemorrhagic infarction/periventricular venous infarction; COL4A1/A2 and COL5A1/A2 genes should be investigated first.

Entrapment and mobilization dynamics during the flow of viscoelastic fluids in natural porous media: A micro-scale experimental investigation

Capillary desaturation process was investigated as a function of wetting phase rheological signatures during the injection of Newtonian and non-Newtonian fluids. Two sets of two-phase imbibition flow experiments were conducted on a water-wet sandstone core sample using brine and viscoelastic polymer solutions. During the experiments, a high-resolution micro-computed tomography scanner was employed to directly map pore-level fluid occupancies within the pore space. The results of the experiments revealed that at a given capillary number, the viscoelastic polymer was more efficient than the brine in recovering the non-wetting oil phase. At low capillary numbers, this is attributed to the improved accessibility of the viscoelastic polymer solution to the entrance of pore elements, which suppressed snap-off events and allowed more piston-like and cooperative pore-body filling events to contribute to oil displacement. For intermediate capillary numbers, the onset of elastic turbulence caused substantial desaturation, while at high capillary numbers, the superimposed effects of higher viscous and elastic forces further improved the mobilization of the trapped oil ganglia by the viscoelastic polymer. In the waterflood, however, the mobilization of oil globules was the governing recovery mechanism, and the desaturation process commenced only when the capillary number reached a threshold value. These observations were corroborated with the pore-level fluid occupancy maps produced for the brine and viscoelastic polymer solutions during the experiments. Furthermore, at the intermediate and high capillary numbers, the force balance and pore-fluid occupancies suggested different flow regimes for the non-Newtonian viscoelastic polymer. These regions are categorized in this study as elastic-capillary- and viscoelastic-dominated flow regimes, different from viscous-capillary flow conditions that are dominant during the flow of Newtonian fluids. Moreover, we have identified novel previously unreported pore-scale displacement events that take place during the flow of viscoelastic fluids in a natural heterogeneous porous medium. These events, including coalescence, fragmentation, and re-entrapment of oil ganglia, occurred before the threshold of oil mobilization was reached under the elastic-capillary-dominated flow regime. In addition, we present evidence for lubrication effects at the pore level due to the elastic properties of the polymer solution. Furthermore, a comparison of capillary desaturation curves generated for the Newtonian brine and non-Newtonian viscoelastic polymer revealed that the desaturation process was more significant for the viscoelastic polymer than for the brine. Finally, the analysis of trapped oil clusters showed that the ganglion size distribution depends on both the capillary number and the rheological properties of fluids.

Break-up and mobilization of DNAPL by acoustic excitation: Experimental evidence and pore network modeling

Dense non-aqueous phase liquids (DNAPLs) are long-term groundwater contaminants due to their high toxicity and slight solubility in water. The use of acoustic waves to remobilize trapped ganglia in subsurface porous systems have some advantages over pre-existing solutions including eliminating the bypassing effect and new environmental hazards. Designing an effective acoustically assisted remediation method for such purposes relies on understanding the underlying mechanisms and developing validated models. In this work, pore-scale microfluidic experiments were run to investigate the interplay between break-up and remobilization under sonication at different levels of flow rate and wettability conditions. Based on the experimental observation and pore-scale physical characteristics, a pore network model was developed and verified against the experimental results. Such a model was developed based on a two-dimensional network and scaled up to three-dimensional networks. In the experiments, processing of two-dimensional images showed that acoustic waves can remobilize trapped ganglia. The other observed effect of vibration is to break up blobs and reduce the mean ganglia size. Recovery enhancements were greater in hydrophilic micromodels as compared to hydrophobic system. A strong correlation was found between the remobilization and breakup indicating that the trapped ganglia are breaking up due to acoustic stimulation firstly and then a background viscous force may get them flowing under the new generated fluid distribution. In modeling, the simulation results of residual saturation reasonably matched with experimental observations. The differences between the prediction by the model and the experimental data at verification points is less than 2% for data before and after the acoustic excitation. The transitions from three-dimensional simulations were used to propose a modified capillary number. This study gives a better understanding of the mechanisms behind the effect of acoustic waves in porous media and provides a predictive tool for evaluating enhancement in fluid displacement.

Management of ganglion by double loop suture technique

Background: Ganglion is a common cystic swelling around wrist presenting in outdoor department, clinical examination is sufficient for making diagnosis of simple cyst, cosmesis and pain are main presenting complain. Treatment includes aspiration with or without injections but has high recurrence rate, surgical excision has low recurrence rate but being invasive there are numerous complications and should be warrant depending on patient complain. Minimal invasive loop suture technique has low recurrence and minimalcomplication. Aims and Objectives: The aim of the study was to manage the ganglion by double loop suture technique. Materials and Methods: One hundred and four patients with volar and dorsal wrist ganglion fulfilling inclusion and exclusion criteria received treatment by minimal invasive loop suture technique, 6-month follow-up was done for reviewing any recurrence of cyst. Results: From these 104 patients, 76 were females and 28 were males, with a median age of 22 years. Ninety-four (90.4%) patients presented with dorsal wrist ganglion and 10 (9.6%) patients had volar wrist ganglion. The size of simple ganglia varied from 10 mm to 32 mm Cosmesis was the most common presenting complaint in 84 patients (80.7%) followed by pain (19.3%). Recurrence of swelling was observed in four patients (3.8%). Complications were encountered in two cases in the form of superficial infection at the site of entry point of threads. Conclusion: Radical surgical excision is gold standard but warranted by patient complains as there are numerous complications. Double loop suture technique is an ambulatory surgical procedure and has very promising results with low recurrence rate and complications.

Endocranial anatomy of Allosaurus supports neural trends among non-avian theropod dinosaurs

ABSTRACT Endocranial cavities preserve a record of neural anatomy often used for hypotheses of behavior in extinct organisms. Two reconstructions of cranial endocasts of Allosaurus fragilis and A. jimmadseni from computed tomography data expand understanding of theropod endocranial anatomy including endocranial volume, inner ear shape, and trigeminal ganglion size. Endocranial and trigeminal ganglion volumes are compared with a sample of birds, crocodylians, and non-avian theropod dinosaurs. Allosaurus is found to have a relatively small trigeminal foramen for its body size when compared with foramina of birds and crocodylians. The inner ear is fragmentary but similar in shape to semicircular canals of other large-bodied theropod dinosaurs. These findings suggest Allosaurus had generalist neural structures relative to other non-avian theropod dinosaurs. Like other large-bodied theropod dinosaurs, Allosaurus likely had a large dural venous sinus, potentially important for brain cooling. Allosaurus did not have a derived sense of facial somatosensation akin to that found in crocodylians or some birds. Additional data like these, collected from other tetanuran dinosaurs, will help clarify the evolution of neurosensory systems in the lineage.

Recording and analysis of slow waves of the small intestine of mice with heart failure.

Gastrointestinal (GI) symptoms in heart failure (HF) patients are associated with increased morbidity and mortality. We hypothesized that HF reduces bioelectrical activity underlying peristalsis. In this study, we aimed to establish a method to capture and analyze slow waves (SW) in the small intestine in mice with HF. We established a model of HF secondary to coronary artery disease in mice overexpressing tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells. The myoelectric activity was recorded from the small intestine in live animals under anesthesia. The low- and high-frequency components of SW were isolated in MATLAB and compared between the control (n=12) and eTNAP groups (n=8). C-kit-positive interstitial cells of Cajal (ICC) and Pgp9.5-positive myenteric neurons were detected by immunofluorescence. Myenteric ganglia were assessed by hematoxylin and eosin (H&E) staining. SW activity was successfully captured in vivo, with both high- and low-frequency components. Low-frequency component of SW was not different between endothelial TNAP (eTNAP) and control mice (mean[95% CI]: 0.032[0.025-0.039] vs. 0.040[0.028-0.052]). High-frequency component of SW showed a reduction eTNAP mice relative to controls (0.221[0.140-0.302] vs. 0.394[0.295-0.489], p < 0.01). Dysrhythmia was also apparent upon visual review of signals. The density of ICC and neuronal networks remained the same between the two groups. No significant reduction in the size of myenteric ganglia of eTNAP mice was observed. A method to acquire SW activity from small intestines in vivo and isolate low- and high-frequency components was established. The results indicate that HF might be associated with reduced high-frequency SW activity.

Residual NAPL Morphology Effects on Electrical Resistivity: Insights From Micromodel Displacement Experiments and Pore Network Simulations

AbstractCharacterizing residual non‐aqueous phase liquids (NAPLs) in porous media is essential for designing contaminated site remediation strategies. The direct current resistivity method is increasingly being used at sites contaminated by NAPLs, which uses the Archie's second law to connect NAPL saturation with the resistivity of porous media. A power‐law relationship connecting the phase morphology measured by Euler characteristic with resistivity has also been observed at the pore‐scale. Because these relationships are limited for porous media with specific wettability, previous research works have demonstrated deviations from Archie's second law in both the laboratory and field experiments. To evaluate the effects of residual NAPL morphology with different wettability on bulk resistivity, we developed two 2D‐micromodels and measured their electrical resistivity and phase morphology during phase displacement under laboratory‐controlled conditions. Furthermore, pore network simulations of a variety of conditions were performed in absence of surface conduction. Results show that NAPL distributed in dead ends of the pore space has limited influence on bulk resistivity since they do not control the current path and voltage distribution. The correlations between resistivity index and Euler characteristic are determined by NAPL ganglia size and pore throat width. A power‐law relationship is found between the Archie's saturation exponent and the average size of the residual NAPL ganglia, indicating that this exponent can be interpreted as the rate of change of the pore water connectivity with saturation. These insights provide a physical framework connecting the morphology and wettability of the NAPL ganglia with the Archie's saturation exponent.

A Stereological Study of the Three Types of Ganglia of Male, Female, and Undifferentiated Scrobicularia plana (Bivalvia).

Simple SummaryIn bivalves, neurotransmitters from neural ganglia modulate gonadal maturation, and the gonadal derived sex-steroids may influence the central nervous system. However, it is unknown whether the ganglia microanatomy varies between sexes or with maturation status, besides the intrinsic differences between ganglia types. Therefore, we conducted a quantitative microscopical study on the ganglia of adult peppery furrow shell. Females show a larger glia-to-neuron numerical ratio. Further, females have a greater ganglionic volume than undifferentiated adults, with males showing intermediate values. These facts indicate that ganglia size is related somehow to maturation. Cell size seems to be the basis of the differences. The three ganglion types differ in total volumes and the volume ratio of the cortex versus the medulla. The pedal and visceral ganglia have more voluminous cortexes and medullae, but more neuronal and non-neuronal cells only in the visceral. The mean number of neural cells ranges from 12,000 to over 68,000. The new data make us wonder about the intricate and integrative neural networks of bivalves and how they relate to unsolved issues, such as nociception. The data should help interpret water pollutants’ impacts on the bivalve nervous system, whereas warning that experimental planning should consider sex and gonadal maturation.Neurotransmitters modulate gonadal maturation in bivalves. However, it remains unclear whether there are differences in the nervous system structure between sexes, maturation, and ganglia. Therefore, a stereological study was conducted on the ganglia of adult peppery furrow shell (Scrobicularia plana). Equal-sized males, females, and undifferentiated (gamete absence) animals were fixed with 10% formalin and processed for light microscopy. They were serially cut into 35 µm paraffin thick sections and stained with hematoxylin-eosin. Sections with cerebral (cerebropleural), pedal, and visceral ganglia were studied. The parameters estimated were the volumes of the ganglia, the total and relative volumes of their cortex (outer layer) and medulla (neuropil), and the total number of cells (neurons, glia, and pigmented) per ganglia and compartment. The volumes and numbers were estimated, respectively, by the Cavalieri principle and by the optical fractionator. Females show a larger glia to neuron numerical ratio. Further, females have a greater ganglionic volume than undifferentiated adults, with males showing intermediate values. These facts indicate that the ganglia size is related somehow to maturation. The cell size forms the basis of the differences because total cellularity is equal among the groups. The three ganglion types differ in total volumes and the volume ratio of the cortex versus the medulla. The greater volumes of the pedal ganglia (vis-a-vis the cerebral ones) and of the visceral ganglia (in relation to all others) imply more voluminous cortexes and medullae, but more neuronal and non-neuronal cells only in the visceral. The new fundamental data can help interpret bivalve neurophysiology.

A Novel Method for Identifying the Transition Zone in Long-Segment Hirschsprung Disease: Investigating the Muscle Unit to Ganglion Ratio.

Hirschsprung disease (HSCR) is characterised by the absence of enteric ganglia along variable lengths of the distal bowel. Current gold standard treatment involves the surgical resection of the defective, aganglionic bowel. Clear and reliable distinction of the normoganglionated bowel from the transition zone is key for successful resection of the entire defective bowel, and the avoidance of subsequent postoperative complications. However, the intraoperative nature of the tissue analysis and the variability of patient samples, sample preparation, and operator objectivity, make reproducible identification of the transition zone difficult. Here, we have described a novel method for using muscle units as a distinctive landmark for quantifying the density of enteric ganglia in resection specimens from HSCR patients. We show that the muscle unit to ganglion ratio is greater in the transition zone when compared with the proximal, normoganglionated region for long-segment HSCR patients. Patients with short-segment HSCR were also investigated, however, the muscle unit to ganglion ratio was not significantly different in these patients. Immunohistochemical examination of individual ganglia showed that there were no differences in the proportions of either enteric neurons or glial cells through the different regions of the resected colon. In addition, we identified that the size of enteric ganglia was smaller for patients that went on to develop HSCR associated enterocolitis; although the density of ganglia, as determined by the muscle unit to ganglia ratio, was not different when compared with patients that had no further complications. This suggests that subtle changes in the enteric nervous system, even in the “normoganglionated” colon, could be involved in changes in immune function and subsequent bacterial dysbiosis.

Elucidating the Role of N‐cadherin during Trigeminal Gangliogenesis

Cadherin‐based adhesion is critical to the formation of multicellular tissues, including the cranial sensory ganglia of the peripheral nervous system. Initial assembly of the cranial trigeminal ganglion, which houses the cell bodies for the trigeminal nerve, relies on the coalescence of N‐cadherin (N‐cad)‐expressing placode cell‐derived neurons and Cadherin‐7‐expressing neural crest cells. The trigeminal ganglion has a role that is primarily sensory, transmitting information on pain, touch, and temperature from different facial regions back to the central nervous system. Proper survival and differentiation of trigeminal neurons relies, in part, upon binding of neurotrophic and other growth factors secreted from target tissues to their cognate receptors found on peripheral axons. These complexes are then trafficked to neuronal cell bodies, resulting in the activation of downstream signaling pathways. Prior studies have shown that N‐cad internalization and trafficking are required for proper neuronal outgrowth. Moreover, N‐cad knockdown in chick trigeminal placode cells leads to early defects in trigeminal ganglion assembly by increasing placodal neuron dispersal. Later functions for N‐cad in chick trigeminal gangliogenesis, however, remain obscure. We hypothesize that N‐cad controls trigeminal ganglion development through the regulation of multiple signaling pathways. To address this, we performed morpholino‐mediated knockdown of N‐cad in chick trigeminal placode cells followed by immunohistochemistry and biochemistry to evaluate trigeminal gangliogenesis. Our preliminary data show that N‐cad depletion has a sustained negative impact on the trigeminal ganglion through cell and non‐cell autonomous effects, resulting in decreased ganglion size, aberrant nerve outgrowth and branching, and reduced levels of Cadherin‐7, neurotrophins and their receptors, and Smad family members. Future studies will aim to elucidate the mechanisms by which N‐cad controls trigeminal ganglion development via these molecules and pathways, including experiments designed to examine protein trafficking in trigeminal neurons. Taken together, our findings reveal potential adhesion‐dependent and ‐independent functions for N‐cad in the trigeminal ganglion, which will aid in the understanding of its tissue‐specific roles. This knowledge will shed light on the etiology of disorders characterized by abnormal neural crest cell and placode cell development and those affecting the peripheral nervous system.

Intra- and extra-capsular ganglia at the gastrocnemius origin and association with meniscal tears and severity of osteoarthritis of the knee joint.

The association between size of ganglia or type of ganglia (intra-articular or extra-articular) and meniscal tears or severity of the osteoarthritis (OA) is not evaluated. To evaluate the prevalence, size, and location of intra- and extra-capsular ganglia at the gastrocnemius origin and to assess their associations with meniscal injury and grades of OA. This study included 301 consecutive patients who had knee pain and had undergone magnetic resonance imaging (MRI) of the knee. We evaluated presence of ganglia at the gastrocnemius muscle origin site and diagnosed whether it was an intra-capsular located or mixed-capsular located (intra-capsular and extra-capsular) and then measured the diameter of each ganglion. After two weeks, we evaluated whether articular cartilage injury existed. The presence of a meniscal tear was also recorded. A total of 186 patients (93%) had intra- and extra-capsular ganglia. Intra-capsular ganglia were found in 183 cases (91%) and mixed-capsular ganglia were found in 16 cases (8%). In cases with intra- and extra-capsular ganglia, more meniscal tears were found (P = 0.029). Intra-capsular ganglia showed more meniscal tears (P = 0.021). Intra-capsular ganglia were more likely to have high-grade OA (P = 0.043). Patients who had a meniscal tear displayed larger-sized ganglia, especially of the intra-capsular type (P = 0.044). Patients with intra- and extra-capsular ganglia, especially of the intra-capsular type, are more likely to have meniscal injury and more severe OA. Patients with a meniscal tear or OA are more likely to have larger intra- and extra-capsular ganglia, especially of the intra-capsular type.

A Full-term Infant with Seizures.

A Full-term Infant with Seizures.