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1.
J Comp Pathol ; 194: 1-6, 2022 Jun.
Article En | MEDLINE | ID: mdl-35577453

A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3+ T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in disturbance of the autonomic nervous system in the gastrointestinal tract, as in ulcerative colitis in humans. Histopathological features in this case differ from those of equine enteric dysautonomia and chronic intestinal pseudo-obstruction, which are characterized by neuronal degeneration and inflammation, respectively, and mostly affect the mural ganglion plexuses. To the best of our knowledge, this is the first report of CD3+ T-lymphocytic extramural enteric ganglioneuritis in equine inflammatory bowel disease.


Colitis, Ulcerative , Horse Diseases , Inflammatory Bowel Diseases , Animals , Chronic Disease , Colitis, Ulcerative/veterinary , Ganglia, Sympathetic/pathology , Horse Diseases/pathology , Horses , Inflammatory Bowel Diseases/veterinary , T-Lymphocytes/pathology
2.
Acta Neuropathol Commun ; 9(1): 187, 2021 11 24.
Article En | MEDLINE | ID: mdl-34819156

In sporadic Creutzfeldt-Jakob disease (sCJD), the pathological changes appear to be restricted to the central nervous system. Only involvement of the trigeminal ganglion is widely accepted. The present study systematically examined the involvement of peripheral ganglia in sCJD utilizing the currently most sensitive technique for detecting prions in tissue morphologically. The trigeminal, nodose, stellate, and celiac ganglia, as well as ganglia of the cervical, thoracic and lumbar sympathetic trunk of 40 patients were analyzed with the paraffin-embedded tissue (PET)-blot method. Apart from the trigeminal ganglion, which contained protein aggregates in five of 19 prion type 1 patients, evidence of prion protein aggregation was only found in patients associated with type 2 prions. With the PET-blot, aggregates of prion protein type 2 were found in all trigeminal (17/17), in some nodose (5 of 7) and thoracic (3 of 6) ganglia, as well as in a few celiac (4 of 19) and lumbar (1 of 5) ganglia of sCJD patients. Whereas aggregates of both prion types may spread to dorsal root ganglia, more CNS-distant ganglia seem to be only involved in patients accumulating prion type 2. Whether the prion type association is due to selection by prion type-dependent replication, or due to a prion type-dependent property of axonal spread remains to be resolved in further studies.


Creutzfeldt-Jakob Syndrome/metabolism , Prion Diseases/metabolism , Prions/metabolism , Trigeminal Ganglion/metabolism , Creutzfeldt-Jakob Syndrome/pathology , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Ganglia, Sympathetic/metabolism , Ganglia, Sympathetic/pathology , Humans , Peripheral Nerves/metabolism , Peripheral Nerves/pathology , Prion Diseases/pathology , Trigeminal Ganglion/pathology
3.
Ann Diagn Pathol ; 52: 151732, 2021 Jun.
Article En | MEDLINE | ID: mdl-33798927

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m2. They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination.


Celiac Artery/pathology , Celiac Plexus/pathology , Fibrosis/pathology , Ganglia, Sympathetic/pathology , Median Arcuate Ligament Syndrome/pathology , Abdominal Pain/etiology , Adult , Body Mass Index , Celiac Artery/surgery , Celiac Plexus/surgery , Constriction, Pathologic/etiology , Female , Fibrosis/surgery , Ganglia, Sympathetic/surgery , Humans , Laparoscopy/methods , Median Arcuate Ligament Syndrome/diagnosis , Median Arcuate Ligament Syndrome/surgery , Middle Aged , Nausea/etiology , Nerve Block/methods , Outcome Assessment, Health Care , Postprandial Period , Robotic Surgical Procedures/methods , Vomiting/etiology , Weight Loss
4.
Vet Res ; 51(1): 82, 2020 Jun 17.
Article En | MEDLINE | ID: mdl-32552868

In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.


Cattle Diseases/epidemiology , Ganglia, Sympathetic/pathology , Neurofibroma/veterinary , Animals , Cattle , Cattle Diseases/etiology , Cohort Studies , Female , Germany/epidemiology , Incidence , Male , Neurofibroma/epidemiology , Neurofibroma/etiology , Risk Factors
5.
Nuklearmedizin ; 59(4): 300-307, 2020 Aug.
Article En | MEDLINE | ID: mdl-32005043

AIM: To check if diffusion weighted imaging (DWI) might be helpful in proper recognition of celiac (CG) and cervicothoracic (CTG) sympathetic ganglia on the whole-body multimodal PSMA-ligand PET/MR imaging, in the view of their common misleading avidity on PET potentially suggestive of malignant lesions, including metastatic lymph nodes. METHODS: The thickness and the level of diffusion restriction was assessed qualitatively and quantitatively in 406 sympathetic ganglia (189 CTG in 101 males and 217 CG in 116 males) on DWI maps (b-value 0 and 800 s/mm2) and apparent diffusion coefficient (ADC) maps (mean ADC) of the whole-body PET/MR 68Ga-PSMA-11 PET/MR. To form a reference group of a matching ganglia size, the smallest lymph node was chosen from each patient with metastases and underwent the same procedure. RESULTS: Very low and low level of diffusion restriction was noted in the majority of sympathetic ganglia (81.0 % CTG, 67.3 % CG, and 73.6 % of all). In the majority (91.7 %) of metastatic lymph nodes the level of diffusion restriction was moderate to high.The mean ADC values in sympathetic ganglia were statistically significantly higher in CTG, CG and all ganglia than in metastatic lymph nodes (p < 0.001; the effect size was large). CONCLUSIONS: Sympathetic celiac and cervicothoracic ganglia present very low and low level of diffusion restriction in visual DWI assessment, and significantly higher than metastatic lymph nodes mean ADC values in the majority of cases, which may serve as additional factors aiding differential diagnosis on multimodal PSMA-ligand PET/MR imaging.Therefore, PSMA-ligand PET/MR appears potentially superior to PSMA-ligand PET/CT in proper identification of sympathetic ganglia.


Gallium Isotopes , Gallium Radioisotopes , Ganglia, Sympathetic/diagnostic imaging , Ganglia, Sympathetic/pathology , Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Adult , Aged , Diffusion , Humans , Ligands , Lymphatic Metastasis , Male , Middle Aged , Prostatic Neoplasms/pathology
6.
Pancreatology ; 20(1): 110-115, 2020 Jan.
Article En | MEDLINE | ID: mdl-31759906

BACKGROUND: Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC). PATIENTS: We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database. RESULTS: Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15). CONCLUSIONS: EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided.


Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/pathology , Ganglia, Sympathetic/pathology , Adult , Aged , Decision Making , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies
7.
Radiol Oncol ; 53(4): 407-414, 2019 10 25.
Article En | MEDLINE | ID: mdl-31652125

Background Detectable uptake of 68Ga-PSMA-ligands in sympathetic ganglia may potentially lead to mistaking them for malignant lesions. Our aim was to investigate the anatomy of cervico-thoracic-ganglia-complex (CTG-C) in the MR part of multimodal 68Ga-PSMA-11 PET/MR imaging, in view of PET factors hindering its proper identification. Patients and methods In 106 patients, 212 sites of the CTG-C were retrospectively reviewed to assess the radiotracer uptake (SUVmax), size, shape, position, symmetry of location and visual uptake intensity. Asymmetry of PSMA-ligand uptake and increased uptake were regarded as risk factors of malignancy. Results In 66.0% left (L) and 53.8% right (R) CTG-C we noticed configurations, resembling the shape of an exclamation-mark, a question-mark, or its part (called "typical"). Tumor-like CTG-C shapes (oval, binodular or longitudinal) were detected in 28.3% L-CTG-C and in 40.6% R-CTG-C. When visual assessment of PET suggested malignancy, the recognition of "typical" shape of underlying CTG-C on MR generated a rise in the accuracy of their proper identification (from 34.4% to 75%, χ2(1) = 70.4; p < 0.001). Recognizing the shape of the CTG-C as "typical" in MR allowed us to classify as "not-suspicious" 61.9% of all CTG-C which were treated as "suspicious" after sole PET assessment. Conclusions The characteristic shape of cervico-thoracic-ganglia-complex (resembling a question-mark, or its part) helps in proper recognition of CTG-C on multimodal whole-body 68Ga-PSMA-ligand PET/MR imaging, when detectable uptake might lead to considering pathology.


Edetic Acid/pharmacokinetics , Ganglia, Sympathetic/anatomy & histology , Lymphatic Metastasis/diagnostic imaging , Membrane Glycoproteins/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Adult , Aged , Diagnosis, Differential , Edetic Acid/analogs & derivatives , Gallium Isotopes , Gallium Radioisotopes , Ganglia, Sympathetic/diagnostic imaging , Ganglia, Sympathetic/pathology , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Prostatic Neoplasms/pathology , Retrospective Studies
8.
J Neuroimmunol ; 337: 577075, 2019 12 15.
Article En | MEDLINE | ID: mdl-31655421

T-cell immune attack of cancer cells underlies the efficacy of immune checkpoint inhibitors in many cancer subtypes, but is not yet well established in the primary brain cancer glioblastoma. Immune checkpoint inhibitor treatments that disinhibit the immune system to enhance immune clearance of cancer have in rare cases resulted in T-cell attack of peripheral ganglia causing lymphocytic ganglionitis. In glioblastoma, lymphocytic ganglionitis has not been reported and checkpoint inhibitors are not routinely used. Here we report a case of glioblastoma not treated with checkpoint inhibitors in which the primary tumor and peripheral ganglia of the celiac and sympathetic chains, as well as myenteric plexus, are infiltrated by CD8+ cytotoxic T-cells. In addition to the marked lymphocytic infiltrates, this case is also notable for an unusually long survival (8 years) after diagnosis with glioblastoma, but an ultimately fatal outcome due to ileus. The findings suggest T-cell immune attack of glioblastoma may prolong survival, but also suggest T-cell autoimmune diseases such as lymphocytic ganglionitis could become a risk with the future use of immune-targeted therapies for glioblastoma.


Brain Neoplasms/pathology , Ganglia, Sympathetic/pathology , Glioblastoma/pathology , Lymphocytes/pathology , Megacolon/pathology , Brain Neoplasms/complications , Brain Neoplasms/immunology , Fatal Outcome , Ganglia, Sympathetic/immunology , Glioblastoma/complications , Glioblastoma/immunology , Humans , Lymphocytes/immunology , Male , Megacolon/etiology , Megacolon/immunology , Middle Aged
9.
Auton Neurosci ; 220: 102558, 2019 09.
Article En | MEDLINE | ID: mdl-31331692

Bladder cystopathy and autonomic dysfunction are common complications of diabetes, and have been associated with changes in ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of ganglionic neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week Leprdb/db mice. Type II diabetes in Leprdb/db animals caused a non-linear change in excitability and firing properties of MPG neurons. At 10 weeks, cells exhibited increased excitability as demonstrated by an increased likelihood of firing multiple spikes upon depolarization, decreased rebound spike latency, and overall narrower action potential half-widths as a result of increased depolarization and repolarization slopes. Conversely, at 21 weeks MPG neurons of Leprdb/db mice reversed these changes, with spiking patterns and action-potential properties largely returning to control levels. These changes are associated with numerous time-specific changes in calcium, sodium, and potassium channel subunit mRNA levels. However, Principal Components Analysis of channel expression patterns revealed that rectification of excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 21-week Leprdb/db neurons. These data indicate that type II diabetes can impact the excitability of post-ganglionic, autonomic neurons of female mice, and suggest that the non-linear progression of these properties with diabetes may be the result of compensatory changes in channel expression that act to rectify disrupted firing patterns of Leprdb/db MPG neurons.


Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Ganglia, Sympathetic/pathology , Ion Channels/metabolism , Neurons/metabolism , Action Potentials/physiology , Animals , Female , Ganglia, Sympathetic/physiopathology , Ion Channels/biosynthesis , Mice , Mice, Mutant Strains , Receptors, Leptin/genetics
10.
Neurol Sci ; 40(9): 1985-1989, 2019 Sep.
Article En | MEDLINE | ID: mdl-31147856

INTRODUCTION: Neuroblastoma ranks third among pediatric malignancies. CASE REPORT: The case of a 3-year-old child is presented, who suddenly had frequent, unproductive, emetic cough; fever; and weight loss. Lung X-ray showed an opacity situated in the posterior superior mediastinum. Thoracic ultrasound revealed a slightly inhomogeneous, hypoechoic mass located in the posterior superior mediastinum. Computed tomography evidenced a tumor mass with homogeneous appearance in the costo-vertebral groove. Histological examination confirmed the diagnosis of ganglioneuroblastoma. CONCLUSION: Although history and clinical examination provided few elements, diagnosis was made based on imaging and histopathological examination.


Ganglia, Sympathetic/pathology , Ganglioneuroblastoma/diagnosis , Peripheral Nervous System Neoplasms/diagnosis , Child, Preschool , Ganglioneuroblastoma/pathology , Ganglioneuroblastoma/surgery , Humans , Male , Peripheral Nervous System Neoplasms/pathology , Peripheral Nervous System Neoplasms/surgery
11.
Vet Pathol ; 56(2): 244-247, 2019 03.
Article En | MEDLINE | ID: mdl-30286693

Equine dysautonomia (grass sickness) is characterized by autonomic neuronal degeneration and is often fatal. As outbreaks occur, rapid diagnosis is essential but confirmation currently requires histological examination. This study evaluated diagnostic accuracy of cytological examination of cranial cervical ganglion (CCG) scrapings for dysautonomia diagnosis. CCG smears from 20 controls and 16 dysautonomia cases were stained with May-Grünwald Giemsa (MGG), hematoxylin and eosin (HE), and cresyl fast violet (CFV), with HE-stained histological sections of CCG as gold standard for diagnosis. Examining all 3 stains together, the sensitivity and specificity were 100%. Occasional individual smears (4/107, 3.7%) were nondiagnostic due to low cellularity, and in a few individual smears the final diagnosis was correct but more tentative (CFV: 5/33 [15.1%], HE: 2/34 [5.9%], and MGG: 4/36 [11.1%]), due to low cellularity or suboptimal cell morphology. CCG cytology was considered reliable for rapid postmortem diagnosis of equine dysautonomia, particularly using MGG.


Ganglia, Sympathetic/pathology , Horse Diseases/diagnosis , Primary Dysautonomias/veterinary , Animals , Case-Control Studies , Coloring Agents , Ganglia, Sympathetic/cytology , Horse Diseases/pathology , Horses , Primary Dysautonomias/diagnosis , Primary Dysautonomias/pathology
13.
Prog. obstet. ginecol. (Ed. impr.) ; 61(6): 565-571, nov.-dic. 2018. ilus, tab, graf
Article En | IBECS | ID: ibc-181391

Background: Ovarian carcinoma is going with peritoneal dissemination in more than a half of the cases at diagnosis. Lymph node involvement is a poor prognostic factor limiting survival. Lumboaortic lymphadenectomy is a part of the therapeutic armamentarium, although there are discrepancies in the selection of patients and prognostic impact. We evaluate some nodal infiltration risk factors for this disease and lymphadenectomy prognostic influence. Material and methods: A retrospective study of 93 patients diagnosed with stage III ovarian cancer between 2006 and 2012. A total of 52 (55.9%) patients were selected to undergo a complete or optimal cytoreduction. Two groups were established according to absence or presence of retroperitoneal lymph nodes during preoperative diagnosis, to assess the objectives of this study. Results: Statistical analysis for clinical and histopathological variables determined prealbumin (p = 0'027) and Ca 125 (p = 0'048) were associated with the risk of nodal infiltration. No significant value was seen in the parameters related to the peritoneal spread of the cancer. Lumboaortic lymphadenectomy improved disease-free survival (25'7 ± 21'4 vs 35'6 ± 22 months) with statistical significance (p = 0'033) but did not appear to achieve outstanding changes in overall survival (39'7 ± 20'1 vs 41'9 ± 20'8 months). Conclusions: A poor nutritional status and high Ca 125 could be predictive factors of lymph node involvement. The performance of a systematic lumboaortic lymphadenectomy seems to increase disease-free survival in association with a properly debulking and absence of severe postoperative complications. A broader recruitment of patients will be needed to know a more accurate pattern of lymph node disease in order to carry out a selective indication for lymphadenectomy


Introducción: el cáncer de ovario se acompaña de diseminación peritoneal en más de la mitad de los casos al diagnóstico. La afectación ganglionar es un factor de mal pronóstico que limita su supervivencia. La linfadenectomía lumboaórtica forma parte del arsenal terapéutico aunque existen discrepancias en la selección de pacientes y su impacto pronóstico. Se pretende evaluar algunos factores de riesgo de infiltración nodal para esta enfermedad y la influencia pronóstica de dicha linfadenectomía. Material y métodos: estudio retrospectivo de 93 pacientes diagnosticados de cáncer ovárico en estadio III entre 2006 y 2012. Fueron seleccionadas 52 (55'9%) enfermas que se beneficiaron de una citorreducción completa u óptima, estableciéndose dos grupos ante la ausencia o presencia de adenopatías retroperitoneales durante el diagnóstico preoperatorio, para contrastar los objetivos del estudio. Resultados: el análisis estadístico de variables clínicas e histopatológicas determinó relación de la prealbúmina (p = 0'027) y Ca 125 (p = 0'048) con el riesgo de infiltración nodal. No se apreció valor significativo en los parámetros relativos a la extensión peritoneal del cáncer. La linfadenectomía lumboaórtica mejoró la supervivencia libre de enfermedad (25'7 ± 21.4 vs 35'6 ± 22 meses) con relevancia estadística (p = 0'033) pero no presentó grandes variaciones en la supervivencia global (39'7 ± 20'1 vs 41'9 ± 20'8 meses). Conclusiones: un estado nutricional deteriorado y un Ca 125 elevado podrían ser factores predictivos de afectación ganglionar. La realización de una linfadenectomía lumboaórtica sistemática parece incrementar la supervivencia libre de enfermedad ante una citorreducción adecuada y ausencia de complicaciones postquirúrgicas graves. Se necesitará un mayor reclutamiento de pacientes para conocer con más exactitud el patrón de enfermedad ganglionar a efectos de una indicación de linfadenectomía más selectiva


Humans , Female , Lymph Node Excision/statistics & numerical data , Ovarian Neoplasms/surgery , Ganglia, Sympathetic/surgery , Peritoneal Neoplasms/surgery , Neoplasm Invasiveness/pathology , Lymphatic Metastasis/pathology , Ovarian Neoplasms/pathology , Ganglia, Sympathetic/pathology , Peritoneal Neoplasms/pathology , Prognosis
14.
Int J Cardiol ; 264: 70-78, 2018 08 01.
Article En | MEDLINE | ID: mdl-29657079

BACKGROUND: Studies have shown regional and functional selectivity of cardiac postganglionic neurones indicating there might exist a similar heterogeneity in spinal segmental preganglionic neurones, which requires further investigation. METHODS: Right and left sympathetic chains were electrically stimulated from T6 to T1 in the innervated isolated rabbit heart preparation (n = 18). Sinus rate, left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic action potential duration, effective refractory period, ventricular fibrillation threshold and electrical restitution were measured. RESULTS: Right sympathetic stimulation had a greater influence on heart rate (T1-T2: right; 59.9 ±â€¯6.0%, left; 41.1 ±â€¯5.6% P < 0.001) and left stimulation had greater effects on left ventricular pressure (T1-T2: right; 20.7 ±â€¯3.2%, left; 40.3 ±â€¯5.4%, P < 0.01) and ventriculo-atrial conduction (T1-T2: right; -6.8 ±â€¯1.1%, left; -15.5 ±â€¯0.2%) at all levels, with greater effects at rostral levels (T1-T3). Left sympathetic stimulation caused shorter monophasic action potentials at the base (T4-T5: right; 119.3 ±â€¯2.7 ms, left; 114.7 ±â€¯2.5 ms. P < 0.05) and apex (T4-T5: right; 118.8 ±â€¯1.2 ms, left; 114.6 ±â€¯2.6 ms. P < 0.05), greater shortening of effective refractory period (T4-T5: right; -3.6 ±â€¯1.3%, left; -7.7 ±â€¯1.8%. P < 0.05), a steeper maximum slope of restitution (T4-T5 base: right; 1.3 ±â€¯0.2, left; 1.8 ±â€¯0.2. P < 0.01. T4-T5 apex: right; 1.0 ±â€¯0.2, left; 1.6 ±â€¯0.3. P < 0.05) and a greater decrease in ventricular fibrillation threshold (T4-T5: right; -22.3 ±â€¯6.8%, left;-39.0 ±â€¯1.7%), with dominant effects at caudal levels (T4-T6). CONCLUSIONS: The preganglionic sympathetic efferent axons show functionally distinct pathways to the heart. The caudal segments (T4-T6) of the left sympathetic chain had a greater potential for arrhythmia generation and hence could pose a target for more focused clinical treatments for impairments in cardiac function.


Ganglia, Sympathetic , Heart , Neurons, Efferent/physiology , Ventricular Fibrillation/physiopathology , Action Potentials/physiology , Animals , Cardiac Electrophysiology/methods , Electric Stimulation/methods , Ganglia, Sympathetic/pathology , Ganglia, Sympathetic/physiology , Ganglia, Sympathetic/physiopathology , Heart/innervation , Heart/physiology , Heart/physiopathology , Heart Rate/physiology , Models, Animal , Rabbits
15.
Clin Auton Res ; 28(2): 223-230, 2018 04.
Article En | MEDLINE | ID: mdl-29396794

OBJECTIVE: Lewy body forms of primary chronic autonomic failure (CAF) such as incidental Lewy body disease (ILBD), Parkinson's disease (PD), and pure autonomic failure evolving into dementia with Lewy bodies (PAF+DLB) feature cardiac sympathetic denervation, whereas multiple system atrophy (MSA) in most cases does not. What links Lewy bodies with cardiac sympathetic denervation in CAF? In familial PD, abnormalities of the alpha-synuclein (AS) gene cause CAF and cardiac sympathetic denervation; and in sporadic PD, brainstem Lewy bodies contain AS co-localized with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Cytotoxicity from AS deposition within sympathetic neurons might explain noradrenergic denervation in Lewy body forms of CAF. We used immunofluorescence microscopy (IM) to explore this possibility in sympathetic ganglia obtained at autopsy from CAF patients. METHODS: Immunoreactive AS and TH were imaged in sympathetic ganglion tissue from 6 control subjects (2 with ILBD), 5 PD patients (1 with concurrent PSP), and 3 patients with CAF (2 PAF + DLB, 1 MSA). RESULTS: MSA involved normal ganglionic TH and no AS deposition. In ILBD TH was variably decreased, and TH and AS were co-localized in Lewy bodies. In PD TH was substantially decreased, and TH and AS were co-localized in Lewy bodies. In PAF + DLB TH was virtually absent, but AS was present in Lewy bodies. The PD + PSP patient had AS co-localized with tau but not TH. CONCLUSIONS: Sympathetic denervation and intraneuronal AS deposition are correlated across CAF syndromes, consistent with a pathogenic contribution of synucleinopathy to cardiac noradrenergic deficiency in Lewy body diseases.


Ganglia, Sympathetic/metabolism , Lewy Body Disease/metabolism , Parkinson Disease/metabolism , Pure Autonomic Failure/metabolism , Tyrosine 3-Monooxygenase/metabolism , alpha-Synuclein/metabolism , Chronic Disease , Ganglia, Sympathetic/chemistry , Ganglia, Sympathetic/pathology , Humans , Lewy Body Disease/pathology , Parkinson Disease/pathology , Pure Autonomic Failure/pathology , Tyrosine 3-Monooxygenase/analysis , alpha-Synuclein/analysis
16.
Neurosci Bull ; 34(1): 85-97, 2018 Feb.
Article En | MEDLINE | ID: mdl-28534262

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.


Ganglia, Sympathetic/pathology , Neurogenic Inflammation/etiology , Pain/etiology , Pain/pathology , Peripheral Nerve Injuries/complications , Action Potentials/physiology , Animals , Disease Models, Animal , Female , Glial Fibrillary Acidic Protein/metabolism , Hyperalgesia/etiology , Ligation/adverse effects , Macrophages/pathology , Male , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Receptors, Antigen, T-Cell, alpha-beta/metabolism
17.
Biomed Res Int ; 2017: 9037476, 2017.
Article En | MEDLINE | ID: mdl-29098163

The aim of the present study was to define changes in the expression of somatostatin (SOM) in the sympathetic perikarya innervating the porcine stomach prepyloric area during acetylsalicylic-acid-induced gastritis (ASA) and experimentally induced hyperacidity (HCL) and following partial stomach resection (RES). On day 1, the stomachs were injected with neuronal retrograde tracer Fast Blue (FB). Animals in the ASA group were given acetylsalicylic acid orally for 21 days. On the 22nd day after FB injection, partial stomach resection was performed in RES animals. On day 23, HCL animals were intragastrically given 5 ml/kg of body weight of a 0.25 M aqueous solution of hydrochloric acid. On day 28, all pigs were euthanized. Then, 14-µm thick cryostat sections of the coeliac-superior mesenteric ganglion (CSMG) complexes were processed for routine double-labelling immunofluorescence. All pathological conditions studied resulted in upregulation of SOM-like (SOM-LI) immunoreactivity (from 14.97 ± 1.57% in control group to 33.72 ± 4.39% in the ASA group, to 39.02 ± 3.65% in the RES group, and to 29.63 ± 0.85% in the HCL group). The present studies showed that altered expression of SOM occurs in sympathetic neurons supplying the prepyloric area of the porcine stomach during adaptation to various pathological insults.


Gastric Mucosa/metabolism , Gastritis/physiopathology , Peptides/immunology , Somatostatin/metabolism , Sympathetic Nervous System/immunology , Animals , Aspirin/analogs & derivatives , Aspirin/toxicity , Ganglia, Sympathetic/metabolism , Ganglia, Sympathetic/pathology , Ganglia, Sympathetic/surgery , Gastritis/chemically induced , Gastritis/immunology , Gastritis/surgery , Neurons/immunology , Neurons/metabolism , Neurons/pathology , Peptides/metabolism , Somatostatin/immunology , Stomach/innervation , Stomach/pathology , Stomach/surgery , Swine , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/pathology
18.
Clin Auton Res ; 27(6): 379-383, 2017 Dec.
Article En | MEDLINE | ID: mdl-28823102

PURPOSE: Primary hyperhidrosis is a pathological disorder of unknown etiology, affecting 0.6-5% of the population, and causing severe functional and social handicaps. As the etiology is unknown, it is not possible to treat the root cause. Recently some differences between affected and non-affected people have been reported. The aim of this review is to summarize these new etiological data. METHODS: Search of the literature was performed in the PubMed/Medline Database and pertinent articles were retrieved and reviewed. Additional publications were obtained from the references of these articles. RESULTS: Some anatomical and pathophysiological characteristics (as well as enzymatic, metabolic, and neurological dysfunctions) have been observed in hyperhidrotic subjects; three main possible etiological factors predominate. A familial trait seems to exist, and genetic loci associated with hyperhidrosis have been identified. Histological differences were observed in sympathetic ganglia of hyperhidrotic subjects: the ganglia were larger and contained a higher number of ganglion cells. A higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis has been reported. CONCLUSIONS: Despite these accumulated data, the etiology of primary hyperhidrosis remains obscure. Nevertheless, three main lines for future research seem to be delineated: genetics, histological observations, and enzymatic studies.


Ganglia, Sympathetic/pathology , Hyperhidrosis/etiology , Hyperhidrosis/pathology , Animals , Humans , Hyperhidrosis/genetics , Sympathectomy/trends
19.
Medicine (Baltimore) ; 96(1): e5856, 2017 Jan.
Article En | MEDLINE | ID: mdl-28072749

The stellate ganglion is a common target to manage neuropathic pain in the upper extremities. However, the effect duration of a single stellate ganglion block is often temporary. To overcome the short-term effects of a single sympathetic block, pulsed radiofrequency (PRF) can be applied. The aim of the present study was to investigate the efficacy of PRF on the cervical sympathetic chain under ultrasound guidance for complex regional pain syndrome (CRPS).Twelve CRPS patients who underwent PRF on the cervical sympathetic chain were enrolled in this retrospective analysis. Under ultrasound guidance, PRF was performed for 420 seconds at 42°C on the C6- and C7-level sympathetic chain.The pain intensity decreased significantly at 1 week after the procedure. Overall, 91.7% of patients experienced at least moderate improvement. A positive correlation was observed between the extent of pain reduction at 1 week after PRF and the degree of overall benefit (r = 0.605, P = 0.037). This reduction in symptoms was maintained for a mean of 31.41 ±â€Š26.07 days after PRF. There were no complications associated with this procedure.PRF on the cervical sympathetic chain, which can be performed easily and safely under ultrasound guidance, should be considered an option for managing CRPS of the upper extremities.


Complex Regional Pain Syndromes , Ganglia, Sympathetic , Pulsed Radiofrequency Treatment/methods , Upper Extremity , Adult , Complex Regional Pain Syndromes/diagnosis , Complex Regional Pain Syndromes/physiopathology , Complex Regional Pain Syndromes/therapy , Female , Ganglia, Sympathetic/diagnostic imaging , Ganglia, Sympathetic/pathology , Humans , Male , Middle Aged , Pain Measurement/methods , Retrospective Studies , Treatment Outcome , Ultrasonography/methods , Upper Extremity/innervation , Upper Extremity/physiopathology
20.
Mol Oncol ; 10(6): 866-78, 2016 06.
Article En | MEDLINE | ID: mdl-26996379

The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease.


Carcinogenesis/metabolism , Ganglia, Sympathetic/pathology , Glutathione/metabolism , N-Myc Proto-Oncogene Protein/metabolism , Neuroblastoma/metabolism , Peripheral Nervous System Neoplasms/metabolism , Animals , Biosynthetic Pathways , Carcinogenesis/pathology , Disease Models, Animal , Ganglia, Sympathetic/cytology , Ganglia, Sympathetic/metabolism , Humans , Metabolome , Mice , Mice, Transgenic , Neuroblastoma/pathology , Peripheral Nervous System Neoplasms/pathology
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