Neural Plexus Research Articles

Morphological pattern of mouse intrinsic cardiac nerve plexus

The study was aimed to determine the 3D organization and immunohistochemistry of intrinsic neural plexus in mouse heart. In a whole heart preparation, intrinsic neural structures were revealed by a histochemical staining for acetylcholinesterase, while the double labeling of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), substance P (SP) and calcitonin gene related peptide (CGRP) was applied to identify immunohistochemically the distribution of adrenergic, cholinergic and peptidergic neural components, respectively. Our findings demonstrate that extrinsic cardiac nerves access the ganglionated nerve plexus of the mouse heart hilum at the right and left cranial veins. Nerves and bundles of nerve fibers extend epicardially from this plexus to atria and ventricles by 5 neural pathways or subplexuses. Generally, the examined hearts from 56 mice contained 19±3 ganglia, in which 1.082±160 neurons reside. Majority of intrinsic neurons (83%) are ChAT(+), 3% ‐ TH(+); 14% – bifenotypic, i.e. they were immunoreactive both for ChAT and TH. The TH(+) epicardial nerve fibers are predominant on the dorsal and ventral sides of left atrium, whereas the most ChAT(+) axons proceed on the heart base toward the large intrinsic ganglia and within epicardium of the root of the right cranial vein. Peptidergic nerve fibers were abundant in the epicardium and within intrinsic ganglia adjacent to the heart hilum. In conclusion, although majority of nerves and neural bundles in the mouse heart are mixed, some of them express either adrenergic or cholinergic phenotype. This study was supported by the Research Council of Lithuania (No. MIP‐11184).

Commentary

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Preliminary experience with external hemipelvectomy for locally advanced and recurrent pelvic carcinoma

Eight highly selected patients are reported, undergoing external hemipelvectomy (EHP) for malignant infiltration of the lumbosacral neural plexus. All patients were evaluated by positron emission tomography-computed tomography (PET-CT), CT and magnetic resonance imaging. No evidence of disseminated disease was found. With agreement by the multidisciplinary team, surgery was performed by a colorectal surgeon and an orthopaedic sarcoma surgeon and, if needed, by an urologist and vascular surgeon. Patients were reconstructed with either a femoral or a gluteal musculocutaneous flap. Of the eight women [median age 54.5 (40-68) years], two had primary carcinoma and six local recurrence of a previously treated carcinoma. R0 was possible in six patients and R1 resection in two. The median duration of hospital stay was 29.5 (17-102) days. The median follow up was 8.3 (4.7-52.8) months. Three patients have died, one from postoperative complications at 5 months and two from recurrence at 5 and 52.8 months. Phantom-limb was experienced in six patients. Four patients received a prosthesis, one is considering this and one does not want a prosthesis. Hemipelvectomy may be considered for a highly selected group of patients with locally advanced carcinoma or recurrence involving the lumbosacral neural plexus.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part I): Anatomy, imaging of the extrapancreatic nerve

Pancreatic carcinoma is an extremely high-grade malignant tumor with fast development and high mortality. The incidence of pancreatic carcinoma continues to increase. Peripancreatic invasion and metastasis are the main characteristics and important prognostic factors in pancreatic carcinoma, especially invasion into the nervous system; pancreatic nerve innervation includes the intrapancreatic and extrapancreatic nerves. A strong grasp of pancreatic nerve innervation may contribute to our understanding of pancreatic pain modalities and the metastatic routes for pancreatic carcinomas. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful techniques for depicting the anatomy of extrapancreatic nerve innervation. The purpose of the present work is to show and describe the anatomy of the extrapancreatic neural plexus and to elucidate its characteristics using CT and MRI, drawing on our own previous work and the research findings of others.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part II): Imaging of pancreatic carcinoma nerve invasion

Computed tomography (CT) and magnetic resonance imaging (MRI) are excellent modalities which have the ability to detect, depict and stage the nerve invasion associated with pancreatic carcinoma. The aim of this article is to review the CT and MR patterns of pancreatic carcinoma invading the extrapancreatic neural plexus and thus provide useful information which could help the choice of treatment methods. Pancreatic carcinoma is a common malignant neoplasm with a high mortality rate. There are many factors influencing the prognosis and treatment options for those patients suffering from pancreatic carcinoma, such as lymphatic metastasis, adjacent organs or tissue invasion, etc. Among these factors, extrapancreatic neural plexus invasion is recognized as an important factor when considering the management of the patients.

Effect of serotonin and calcium on the supercontractile muscles of the adult blowfly crop

Bioassays and electrophysiological recordings were conducted to determine the role of serotonin and calcium on the supercontractile pump muscles of the diverticulated crop of adult blowflies. Using in situ crop preparations, serotonin was found to significantly increase the rates of contractions of a specific pump in the crop wall, pump P4. The addition of the serotonin antagonist, mianserin, or calcium free saline, both significantly reduced the contraction rates of this pump. Recordings, using suction electrodes from pump P4, confirm the in situ bioassay data and show that serotonin promotes muscle activity in empty crops in which no pump activity is normally observed. Moreover, our data indicate the crucial role of extracellular calcium ions in crop pump contractile activity. These results provide new information on how the crop of adult dipterans is modulated and suggest that serotonin, possibly supplied by neurons in the thoracico-abdominal neural plexus, may be involved in modulating the pumping of crop contents into the midgut for digestion or triggering antiperistalsis from the foregut in the process known as regurgitation or ‘bubbling’.

Is celiac axis resection justified for T4 pancreatic body cancer?

The clinical impact of the distal pancreatectomy with en-bloc celiac axis resection for locally advanced pancreatic body cancer remains unclear. We reviewed the records of 13 patients who underwent distal pancreatectomy-celiac axis resection between 1991 and 2009, 58 patients who underwent distal pancreatectomy for pancreatic body cancer involving major vessels, the extrapancreatic neural plexus or other organs (T4 according to the Japanese stage classification) between 1991 and 2009, and 24 patients with unresectable locally advanced pancreatic cancer without distant metastases (unresectable group) between 2001 and 2009. The clinicopathologic factors and overall survival among the 3 groups were compared. The distal pancreatectomy-celiac axis resection group was associated with a significantly higher incidence of morbidity (92% vs 60%, P = .03) and positive surgical margins (69% vs 26%, P = .003) than the distal pancreatectomy group; however, no survival difference was found between the 2 groups. No survivor has lived more than 3 years after operation in the distal pancreatectomy-celiac axis resection group. The distal pancreatectomy-celiac axis resection group had a significantly better prognosis than the unresectable group (median survival time, 20.8 vs 9.8 months; P = .01). Aggressive resection for T4 pancreatic body cancer by distal pancreatectomy-celiac axis resection can be justified for otherwise unresectable tumors. The surgical indication should be evaluated carefully because of the higher incidence of morbidity and lower incidence of curability compared with distal pancreatectomy, as well as because there have been no long-term survivors so far.

Trigeminal artery: a review of normal and pathological features

Carotid-vertebrobasilar anastomoses-the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries-serve as transitory channels between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery, when the human embryo reaches about 4-mm length. Normal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the trigeminal artery are described according to personal and literature data. Many arteries of similar origin and course are also noted in the differential diagnosis of the trigeminal artery. The persistent primitive trigeminal artery, as the most commonly carotid-vertebrobasilar anastomosis, has a reported incidence of 0.03-2.2% in the literature. There is female sex predilection, and it may be discovered in patients of any age, on either side, and in association with many vascular variants. Although the significance of persistent primitive trigeminal artery regarding the development of an aneurysm or association with another pathological condition may not be clear, its (ab)normal morphology is the inspiration for anatomists, especially for neurosurgeons, before planning diagnostic and therapeutic procedures.

Enhanced Gastric Ghrelin Production and Secretion in Rats with Gastric Outlet Obstruction

Ghrelin has distinct effects on gastrointestinal motility through the vagus nerve and gastric excitatory neural plexus. The objectives of this study were to investigate the dynamics of ghrelin and expression of neuromuscular markers in a newly established surgically manipulated rat model of gastric outlet obstruction (GOO), akin to the pyloric stricture associated with duodenal ulcer, advanced gastric cancer, and other conditions, in the clinical setting. The rats were divided into two groups, a control group (sham operation) and the GOO group (proximal duodenal stricture). The animals were sacrificed 2 weeks after the operation. Plasma and gastric ghrelin were measured by radioimmunoassay. mRNA expression in the stomach of neural choline acetyltransferase (ChAT), c-kit, and membrane-bound stem cell factor (SCF) were analyzed by quantitative RT-PCR. In addition, gastric mRNA expression of the aforementioned were also evaluated 60 min after intraperitoneal administration of a synthetic GHS-R1a antagonist ([D: -Lys3] GHRP-6 6.0 mg/kg). Mechanical GOO induced increases of fasting plasma ghrelin levels and hyperplasia of the gastric muscle layers, with enhanced expression of the gastric neuromuscular markers. Administration of [D: -Lys3] GHRP-6 normalized the enhanced expression of c-kit and SCF. GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.

Implication on Bariatric Surgery by Disregarded Neural Related Structures in the Hepato-Bilio-Pancreas-Gastro-Intestinal Tract in the Rat

Purpose: The aim of this report is to describe essentially macroscopic anatomical findings; secondarily, some microscopic details, of an evaluation carried out in 300 Wistar rats. This approach was restricted primarily to the neural autonomic innervation of the hepato-bilio-pancreato-gastro-intestinal tract. Methods: In male animals, body weight 150 to 600 g, under eter or tiopental anesthesia, with delicate instruments and the support of a dissecting microscope (Wild), a microscopic analysis (linear neuronal counting) of the submucous and the myenteric ganglionated plexus was performed, respectively, in the duodenal and the stomach antral segment. Results:Table 1. Emphasis was put on several structures, unexpectedly disregarded in the literature, like, e.g, the diagonal antral band (DAB), a connective nervous band extended from the antral-fundic-junction(AFJ) up to the pylorus; the pre-bile duct-nodular-plexus(PBDNP); the neural fibers that jump the duodeno-pancreatic-cleft-plexus (DPCP), first described in the literature by our group in the sixties; the peri-Vaterian-Center (PVC), with its rich neural density, considered a real autonomic -neural-brain (ANB), and a main starting trigger of autonomic-arc-reflexes, primarily upon the pancreatic “revolver”, pivotal background of a model to mimick human biliary acute pancreatitis; the peculiar arrangement of the celiac ganglia and their linking with the PVC through the perivascular neural network of the inferior pancreatico-duodenal-artery(IPDA). In the PVC and the AFJ a greater linear neuronal counting, respectively, of the submucous and myenteric ganglia when compared with their adjacent zones.Table 1: Oral glucose tolerance test- cumulative value 60 minConclusion: The section and reanastomosis at the level of the AFJ is an inducer of antral peptic ulcers that mimick the human one. The PBDNP and the DAB constitute a “carrrefour” of nerve fibers coming from different sources. Neural impulses, either sympathetic and/or peptidergic, starting from them, the same as those originated from th or the DPCP, modulate, at the level of the neural plexuses of the biliary tract and the hepatic gland, their autonomic neural tone background. The surgical interruption of this modulation, e.g, through a “cicatricial barrier” in what we have called the enteric neural plexus freeway (ENPF), induce trophic changes of the pancreatic gland, and, through an enhancement of the hepatic cholinergic tone an increased release of the Lautt postulated factor (hepatic-insulin-sensitizing-substance, HISS) and, consequently, an improved response of the insulin receptors primarily in the skeletal muscle. The latter, if confirmed in humans, might undoubtedly constitute a much simpler and less dangerous approach to the treatment of morbid obesity in the field of bariatric surgery.

Aging and gastrointestinal neuromuscular function: insights from within and outside the gut

Understanding the effects of aging on the gut neuromuscular axis is of growing and profound importance in light of demographic data demonstrating a steady increase in the aged population globally. Likely areas of significant importance include the potential effects of aging on the extrinsic and intrinsic innervations, smooth muscle function in the human colon, and determination of whether specific biomarkers can be identified in the gut neural plexi, ICC, glial cells or smooth muscle that predict the onset of neurodegeneration. Age-related neuronal losses occur in both the myenteric plexus and submucosal plexus. In general, these losses start in adulthood and progress during the lifespan and involve cholinergic neurons predominately. Parallel age-dependent loss of enteric glia is also observed. The drop-out of these cell populations follows an oral-anal gradient, with greater losses noted distally. Dystrophic axonal swelling and dilated varicosities also increase in an age-dependent manner in the extrinsic innervations (vagal, DRG and sympathetic pathways), as well as, nitrergic neurons in the gut. Advanced age is associated with increased oxidative stress and mitochondrial dysfunction at the cellular level, culminating in disequilibrium between cytoprotective and cytotoxic pathways favoring the latter. Caloric restriction and/or diets supplemented with specific nutrients may help attenuate the effects of aging on neuromuscular function.

Transplantation of Neonatal Gut Neural Crest Progenitors Reconstructs Ganglionic Function in Benzalkonium Chloride-Treated Homogenic Rat Colon

To value the possibility and the future feasibility of the use of autograft cells transplantation in disorders of the enteric neural system, we postulate that isolated neonatal nongenetically modified neural crest progenitors could survive and differentiate into neurons and glia in homogenic denervated rats and, therefore, restore partial intestinal function after transplantation. Neural crest progenitors were isolated from neonatal rats. After passages, the cells were labeled with CM-DiI. The labeled cells were then delivered into the muscular distal denervated colon of rats whose neural plexuses were eliminated using benzalkonium chloride. The treated colons of recipients were harvested at 1, 4, and 8 wk, and identified by immunofluorescent staining. The physiologic and functional improvements on treated colons were well examined after transplantation 8 wk. Progenitors could generate neurospheres and differentiate into neurons and glia in vitro. After transplantation, red fluorescent cells were observed in the injected tissue for up to 8 wk, and they differentiated into neurons and glia in the host colon. Functional examinations indicated that symptoms and intestinal dysfunction of the denervated model were reversed. We provide herein further evidence that autologous cell transplantation is a feasible therapy for enteric nervous system disorders.

Physiology of the intrinsic cardiac nervous system

The article entitled “Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations” by Rysevaite et al1 in this issue of Heart Rhythm depicts the locations of ganglia and interconnecting nerve trunks within the heart of a small mammalian model—that of the mouse. The authors also have characterized a few of the neurochemicals therein, ones that are known to be associated with somata and axons of the mammalian intrinsic cardiac nervous system.

Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations

The intrinsic neural plexus of the mouse heart has not been adequately investigated despite the extensive use of this species in experimental cardiology. The purpose of this study was to determine the distribution of cholinergic, adrenergic, and sensory neural components in whole-mount mouse heart preparations using double immunohistochemical labeling. Intrinsic neurons were concentrated within 19 ± 3 ganglia (n = 20 mice) of varying size, scattered on the medial side of the inferior caval (caudal) vein on the right atrium and close to the pulmonary veins on the left atrium. Of a total of 1,082 ± 160 neurons, most somata (83%) were choline acetyltransferase (ChAT) immunoreactive, whereas 4% were tyrosine hydroxylase (TH) immunoreactive; 14% of ganglionic cells were biphenotypic for ChAT and TH. The most intense ChAT staining was observed in axonal varicosities. ChAT was evident in nerve fibers interconnecting intrinsic ganglia. Both ChAT and TH immunoreactivity were abundant within the nerves accessing the heart. However, epicardial TH-immunoreactive nerve fibers were predominant on the dorsal and ventral left atrium, whereas most ChAT-positive axons proceeded on the heart base toward the large intrinsic ganglia and on the epicardium of the root of the right cranial vein. Substance P-positive and calcitonin gene-related peptide-immunoreactive nerve fibers were abundant on the epicardium and within ganglia adjacent to the heart hilum. Small intensely fluorescent cells were grouped into clusters of 3 to 8 and were dispersed within large ganglia or separately on the atrial and ventricular walls. Although some nerves and neuronal bundles of the mouse epicardial plexus are mixed, most express either adrenergic or cholinergic markers. Therefore, selective stimulation and/or ablation of the functionally distinct intrinsic neural pathways should allow the study of specific effects on cardiac function.

Neural System Antigens Are Recognized by Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia

Endemic pemphigus foliaceus (EPF), is also known as "fogo selvagem" or "wild fire," reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens. We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p<0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy. Our findings may explain for the first time the "pose of pemphigus," representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the "burning sensation" encountered in EPF disease.

Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart

Both normal and genetically modified mice are excellent models for investigating molecular mechanisms of arrhythmogenic cardiac diseases that may be associated with an imbalance between sympathetic and parasympathetic nervous input to the heart. The purpose of this study was to (1) determine the structural organization of the mouse cardiac neural plexus, (2) identify extrinsic neural sources and their relationship with the cardiac plexus, and (3) reveal any anatomic differences in the cardiac plexus between mouse and other species. Cardiac nerve structures were visualized using histochemical staining for acetylcholinesterase (AChE) on whole heart and thorax-dissected preparations derived from 25 mice. To confirm the reliability of staining parasympathetic and sympathetic neural components in the mouse heart, we applied a histochemical method for AChE and immunohistochemistry for tyrosine hydroxylase (TH) and/or choline acetyltransferase (ChAT) on whole mounts preparations from six mice. Double immunohistochemical labeling of TH and ChAT on AChE-positive neural elements in mouse whole mounts demonstrated equal staining of nerves and ganglia for AChE that were positive for both TH and ChAT. The extrinsic cardiac nerves access the mouse heart at the right and left cranial veins and interblend within the ganglionated nerve plexus of the heart hilum that is persistently localized on the heart base. Nerves and bundles of nerve fibers extend epicardially from this plexus to atria and ventricles by left dorsal, dorsal right atrial, right ventral, and ventral left atrial routes or subplexuses. The right cranial vein receives extrinsic nerves that mainly originate from the right cervicothoracic ganglion and a branch of the right vagus nerve, whereas the left cranial vein is supplied by extrinsic nerves from the left cervicothoracic ganglion and the left vagus nerve. The majority of intrinsic cardiac ganglia are localized on the heart base at the roots of the pulmonary veins. These ganglia are interlinked by interganglionic nerves into the above mentioned nerve plexus of the heart hilum. In general, the examined hearts contained 19 ± 3 ganglia, giving a cumulative ganglion area of 0.4 ± 0.1 mm(2). Despite substantial anatomic differences in ganglion number and distribution, the structural organization of the intrinsic ganglionated plexus in the mouse heart corresponds in general to that of other mammalian species, including human.

Supernumerary Intestinal Muscle Coat in a Patient with Hirschsprung Disease/Mowat-Wilson Syndrome

We present the 1st case report of an additional enteric smooth muscle layer in a patient with Mowat-Wilson syndrome and Hirschsprung disease. After resection of the aganglionic colon at the age of 5 months, our patient initially suffered from intermittent constipation, and subsequently by the age of 5 years, he developed ongoing diarrhea requiring medical treatment for more than a decade. Although the exact mechanism of abnormal gut motility in this case is unknown, we postulate that the supernumerary muscle and its associated neural plexus may be responsible for the patient's unusual late complication in treated Hirschsprung disease.

Biomechanics of Disc Arthroplasty: What Can Be Done to Improve Results: Present and Future Perspectives

Current lumbar total disc replacement (TDR) devices require an anterior approach for implantation. The anterior approach to place lumbar TDR devices has inherent biomechanical limitations and surgical risks. Within the possible intraoperative issues are: the damage to various abdominal structures, such to the grand vessels, to bowel components and to the sympathetic neural plexus, without mentioning the long discharge and rehabilitation time. Besides the surgical risks, there is resection of the anterior longitudinal ligament (ALL).

Retrograde Dissemination Through Sacral Neural Pathways: Mechanism of Action for Botulinum Toxin Type A in Concomitant Neuropathic Bladder and Bowel Dysfunction

Purpose In our two previous studies with intravesical botulinum toxin type A (BTX-A) injection and electromotive BTX-A administration in children with myelomeningocele and neurogenic detrusor overactivity, notable improvement in concomitant bowel dysfunction occurred. The exact mechanism for this observation is still unclear but the effect of toxin on common neural pathways for urinary and bowel function and the diffusion of toxin to bladder's contiguous structures are existing hypotheses. This experimental model aimed at determining the validity of current hypotheses. Material and Methods Ten male white New Zealand rabbits were divided in two equal groups: the first group received intravesical 10 IU/kg BTX-A through a specific catheter for electromotive drug administration. A maximum current of 4 mA for 15 min was delivered to the drug solution. In another group, the electrical current with similar characteristics was delivered to the saline-filled bladder. Then, biopsies from the bladder wall and bladder's contiguous structures including intestinal wall lying posterior to the bladder, pelvic floor muscles, sacral neural plexus, and anal sphincter were taken and then submitted for immunohistochemical analysis. Results Botulinum toxin penetrated through muscularis layer of the bladder wall in BTX-A group. The toxin was not present in pelvic floor muscles, intestinal wall, and anal sphincter. The toxin was detected in sacral neural plexus in BTX-A group. Conclusions Botulinum toxin type A acts on neuromuscular junction. Current study suggests that retrograde dissemination of toxin through upper neural pathways which also control bowel motor function can justify simultaneously improved bladder and bowel function.

GABA and glutamate immunoreactivity in tentacles of the sea anemone Phymactis papillosa (LESSON 1830)

Sea anemones have a structurally simple nervous system that controls behaviors like feeding, locomotion, aggression, and defense. Specific chemical and tactile stimuli are transduced by ectodermal sensory cells and transmitted via a neural network to cnidocytes and epithelio-muscular cells, but the nature of the neurotransmitters operating in these processes is still under discussion. Previous studies demonstrated an important role of peptidergic transmission in cnidarians, but during the last decade the contribution of conventional neurotransmitters became increasingly evident. Here, we used immunohistochemistry on light and electron microscopical preparations to investigate the localization of glutamate and GABA in tentacle cross-sections of the sea anemone Phymactis papillosa. Our results demonstrate strong glutamate immunoreactivity in the nerve plexus, while GABA labeling was most prominent in the underlying epithelio-muscular layer. Immunoreactivity for both molecules was also found in glandular epithelial cells, and putative sensory cells were GABA positive. Under electron microscopy, both glutamate and GABA immunogold labeling was found in putative neural processes within the neural plexus. These data support a function of glutamate and GABA as signaling molecules in the nervous system of sea anemones.