Neuroprotective effects of metallothionein against rotenone-induced myenteric neurodegeneration in parkinsonian mice.

PubMed

Murakami, Shinki; Miyazaki, Ikuko; Sogawa, Norio; Miyoshi, Ko; Asanuma, Masato

2014-10-01

Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice.

R-type Ca(2+) channels contribute to fast synaptic excitation and action potentials in subsets of myenteric neurons in the guinea pig intestine.

PubMed

Naidoo, V; Dai, X; Galligan, J J

2010-12-01

R-type Ca(2+) channels are expressed by myenteric neurons in the guinea pig ileum but the specific function of these channels is unknown. In the present study, we used intracellular electrophysiological techniques to determine the function of R-type Ca(2+) channels in myenteric neurons in the acutely isolated longitudinal musclemyenteric plexus. We used immunohistochemical methods to localize the Ca(V)2.3 subunit of the R-type Ca(2+) channel in myenteric neurons. We also studied the effects of the non-selective Ca(2+) channel antagonist, CdCl₂ (100 μmol L⁻¹), the R-type Ca(2+) channel blockers NiCl₂ (50 μmol L⁻¹) and SNX-482 (0.1 μmol L⁻¹), and the N-type Ca(2+) channel blocker x-conotoxin GVIA (CTX 0.1 μmol L⁻¹) on action potentials and fast and slow excitatory postsynaptic potentials (fEPSPs and sEPSPs) in S and AH neurons in vitro. Ca(V)2.3 co-localized with calretinin and calbindin in myenteric neurons. NiCl₂ and SNX-482 reduced the duration and amplitude of action potentials in AH but not S neurons. NiCl₂ inhibited the afterhyperpolarization in AH neurons. x-conotoxin GVIA, but not NiCl₂, blocked sEPSPs in AH neurons. NiCl₂ and SNX-482 inhibited cholinergic, but not cholinergic/purinergic, fEPSPs in S neurons. These data show that R-type Ca(2+) channels contribute to action potentials, but not slow synaptic transmission, in AH neurons. R-type Ca(2+) channels contribute to release of acetylcholine as the mediator of fEPSPs in some S neurons. These data indicate that R-type Ca(2+) channels may be a target for drugs that selectively modulate activity of AH neurons or could alter fast synaptic excitation in specific pathways in the myenteric plexus.

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis

PubMed Central

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Ibba-Manneschi, Lidia

2015-01-01

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin-embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility. PMID:25283476

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allescher, H.D.; Ahmad, S.; Classen, M.

Receptor binding of the opioid receptor antagonist, ({sup 3}H)diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker ({sup 3}H)saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg)more » and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu (morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using ({sup 3}H) ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196.« less

Expression of the P2X2 receptor in different classes of ileum myenteric neurons in the female obese ob/ob mouse

PubMed Central

Mizuno, Márcia Sanae; Crisma, Amanda Rabello; Borelli, Primavera; Castelucci, Patricia

2012-01-01

AIM: To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system abnormalities such as altered motility. METHODS: The study examined the distribution of the P2X2 receptor (P2X2R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X2R with neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice. In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm2) and area profile (μm²) of P2X2R-positive neurons. In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NADH) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and area. RESULTS: In the present study, we observed a 29.6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG). In addition, the average small intestine area was increased by approximately 29.6% in the OG compared to the CG. Immunoreactivity (IR) for the P2X2R, nNOS, ChAT and CalR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups. This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes. P2X2R-IR was observed to co-localize 100% with that for nNOS, ChAT and CalR in neurons of both groups. In the ob/ob group, however, we observed that the neuronal density (neuron/cm2) of P2X2R-IR cells was increased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice. The neuronal density of CalR-IR neurons was not different between the groups. Morphometric studies further demonstrated that the cell body profile area (μm²) of nNOS-IR, ChAT-IR and CalR-IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls. Staining for NADH diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NADH-diaphorase positive neurons in the myenteric ganglia revealed an overall similarity between the two groups. CONCLUSION: We demonstrate increases in P2X2R expression and alterations in nNOS, ChAT and CalR IR in ileal myenteric neurons of female ob/ob mice compared to wild-type controls. PMID:23002338

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis.

PubMed

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Ibba-Manneschi, Lidia

2015-01-01

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin-embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

LOCALIZATION OF CALCITONIN RECEPTOR-LIKE RECEPTOR (CLR) AND RECEPTOR ACTIVITY-MODIFYING PROTEIN 1 (RAMP1) IN HUMAN GASTROINTESTINAL TRACT

PubMed Central

Cottrell, Graeme S.; Alemi, Farzad; Kirkland, Jacob G.; Grady, Eileen F.; Corvera, Carlos U.; Bhargava, Aditi

2012-01-01

Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR•RAMP1 in human disease, little is known about its distribution in the human gastrointestinal (GI) tract, where it participates in inflammation and pain. In this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human stomach, ileum and colon by RT-PCR. We next characterized antibodies that we generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin-immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve bundles in the myenteric plexus and nerve fibers throughout the circular and longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR was found in nerve varicosities of the myenteric plexus and surrounding submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize, but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a functional CGRP receptor were clearly localized in myenteric plexus, where they may form functional cell-surface receptors. IMD, another member of calcitonin peptide family was also found in close proximity to CLR, and like CGRP, did not co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be released locally, where they can mediate their effect on their receptors regulating diverse functions such as inflammation, pain and motility. PMID:22484227

Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

PubMed

Rumessen, J J; Vanderwinden, J-M; Horn, T

2010-10-01

Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.

Qualitative and quantitative analysis of tachykinin NK2 receptors in chemically defined human colonic neuronal pathways.

PubMed

Jaafari, Nadia; Khomitch-Baud, Alexandra; Gilhodes, Jean-Claude; Hua, Guoqiang; Julé, Yvon

2008-04-01

The involvement of NK2 receptors (NK2r) in the neuroregulation of human colonic motility has been mainly assessed by using pharmacological approaches. The aim of this study was to characterize the intramural neurons and nerve varicosities expressing NK2r in human colonic neuronal pathways. Neuronal coding in the myenteric plexus and external muscle layers was identified on the basis of the patterns of colocalization of tachykinins (TK), vesicular acetylcholine transporter (VAChT), nitric oxide synthase (NOS), glutamate decarboxylase (GAD), and vasoactive intestinal peptide (VIP) with NK2r immunoreactivity. The proportions of chemically defined synaptophysin-immunoreactive nerve varicosities were accurately determined by using specific software. NK2r immunoreactivity was detected in the soma of many myenteric neurons (71.8%). A large proportion of these neurons was immunoreactive to VAChT (39.3%), TK (30%), and GAD (23.5%) and, to a lesser extent, to NOS and VIP. The proportions of nerve varicosities expressing NK2r showed significant regional differences: the highest proportion (59.8%) was located in the myenteric plexus. High proportions of the myenteric nerve varicosities expressing NK2r were immunoreactive to VIP (80.9%) and NOS (77.9%), and lower proportions were recorded with VAChT, TK, and GAD. In the circular and longitudinal muscle layers, the proportions of nerve varicosities expressing NK2r were 49.6% and 45.3%, respectively. The chemically defined intramuscular varicosities were closely apposed to smooth muscle cells expressing NK2r. In conclusion, the data obtained in this study, in which the expression of NK2r was mapped in the human colonic neuronal pathways, confirm that these receptors are involved in the neuroneuronal and neuromuscular processes regulating human colonic motility. Copyright 2008 Wiley-Liss, Inc.

Endocrine cells in the denervated intestine

PubMed Central

Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

2000-01-01

This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusunoki, M.; Tsai, L.H.; Taniyama, K.

1986-07-01

Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10 to 10 W M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10 to 10 W M) induced a concentration-dependent increase in the release of (TH)ACh from LM preparations preloaded with (TH)choline. The VIP-evoked (TH)ACh release was inhibited by removal of CaS from the perfusion medium and by treatmentmore » with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked (TH)ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or (D-ProS, D-Trp/sup 7,9/)substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.« less

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

PubMed Central

Sjölund, K; Schaffalitzky, O B; Muckadell, D E; Fahrenkrug, J; Håkanson, R; Peterson, B G; Sundler, F

1983-01-01

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6192043

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

PubMed Central

Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

2016-01-01

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine.

PubMed

Vicentini, Geraldo E; Fracaro, Luciane; de Souza, Sara R G; Martins, Heber A; Guarnier, Flávia A; Zanoni, Jacqueline N

2016-01-01

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress.

No neuronal loss, but alterations of the GDNF system in asymptomatic diverticulosis.

PubMed

Barrenschee, Martina; Wedel, Thilo; Lange, Christina; Hohmeier, Ines; Cossais, François; Ebsen, Michael; Vogel, Ilka; Böttner, Martina

2017-01-01

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor known to promote the survival and maintenance of neurons not only in the developing but also in the adult enteric nervous system. As diverticular disease (DD) is associated with reduced myenteric neurons, alterations of the GDNF system were studied in asymptomatic diverticulosis (diverticulosis) and DD. Morphometric analysis for quantifying myenteric ganglia and neurons were assessed in colonic full-thickness sections of patients with diverticulosis and controls. Samples of tunica muscularis (TM) and laser-microdissected myenteric ganglia from patients with diverticulosis, DD and controls were analyzed for mRNA expression levels of GDNF, GFRA1, and RET by RT-qPCR. Myenteric protein expression of both receptors was quantified by fluorescence-immunohistochemistry of patients with diverticulosis, DD, and controls. Although no myenteric morphometric alterations were found in patients with diverticulosis, GDNF, GFRA1 and RET mRNA expression was down-regulated in the TM of patients with diverticulosis as well as DD. Furthermore GFRA1 and RET myenteric plexus mRNA expression of patients with diverticulosis and DD was down-regulated, whereas GDNF remained unaltered. Myenteric immunoreactivity of the receptors GFRα1 and RET was decreased in both asymptomatic diverticulosis and DD patients. Our data provide evidence for an impaired GDNF system at gene and protein level not only in DD but also during early stages of diverticula formation. Thus, the results strengthen the idea of a disturbed GDNF-responsiveness as contributive factor for a primary enteric neuropathy involved in the pathogenesis and disturbed intestinal motility observed in DD.

Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus

PubMed Central

Izumi, Noriaki; Matsuyama, Hayato; Ko, Mifa; Shimizu, Yasutake; Takewaki, Tadashi

2003-01-01

Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 μs, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones. PMID:12813149

Hexamethonium-induced augmentation of the electrical twitch response in the guinea-pig ileum longitudinal muscle-myenteric plexus strip.

PubMed

Donnerer, Josef; Liebmann, Ingrid; Holzer-Petsche, Ulrike

2014-08-08

Longitudinal muscle-myenteric plexus strips of the guinea-pig ileum were used to investigate the nature of the hexamethonium-induced augmentation of the twitch response. All preparations were set up in Tyrode solution and intermittent longitudinal twitch contractions were evoked by single pulse electrical field stimulation. Hexamethonium, a blocker of nicotinic ganglionic transmission, at 300 μmol/l and 1 mmol/l augmented the twitch contractions by 21% and 35%, respectively. First we tested for a possible nicotinic drive onto an inhibitory neuronal component to the longitudinal smooth muscle cells. However, guanethidine (5 μmol/l), naloxone (1 μmol/l), or l-NAME (300 μmol/l) were without effect on the hexamethonium-induced augmentation. The P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), 25-100 μmol/l, without altering the control twitch responses, dose-dependently reduced the hexamethonium-induced augmentation; at 100 μmol/l a statistically significantly inhibition was observed. Based on these functional experiments we found no evidence that blocking nicotinic transmission removed a tonic adrenergic, opioidergic or nitrergic inhibitory input to the longitudinal muscle. However, we provide evidence for a hexamethonium-induced augmentation of the P2 purinergic input to cholinergic motoneurons of the guinea-pig ileum longitudinal muscle. The P2-nicotinic receptor interaction presents a novel modulatory mechanism to cholinergic myenteric motor neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barker, L.A.; Ebersole, B.J.

1982-04-01

Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N . 7) and the Hill coefficientmore » was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N . 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.« less

Toxicokinetics of lambda-cyhalothrin in rats.

PubMed

Anadón, A; Martínez, M; Martínez, M A; Díaz, M J; Martínez-Larrañaga, M R

2006-08-01

The toxicokinetics of lambda-cyhalothrin after single 20 mg kg(-1) oral and 3 mg kg(-1) intravenous doses were studied in rats. Serial blood samples were obtained after oral and intravenous administration. Liver, brain, spinal cord, sciatic nerve, vas deferens, anococcygeus and myenteric plexus tissue samples were also collected. Plasma, liver, hypothalamus, cerebellum, medulla oblongata, frontal cortex, striatum, hippocampus, midbrain, spinal cord, vas deferens, anococcygeus, myenteric plexus and sciatic nerve concentrations of lambda-cyhalothrin were determined by HPLC. The plasma and tissue concentration-time data for lambda-cyhalothrin were found to fit a two-compartment open model. For lambda-cyhalothrin, the elimination half-life (T1/2beta) and the mean residence time from plasma were 7.55 and 8.55 h after i.v. and 10.27 and 14.43 h after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.060l h(-1)kg(-1). After i.v. administration, the apparent volume of distribution and at steady state were 0.68 and 0.53l kg(-1), suggesting a diffusion of the pyrethroid into tissue. After oral administration, lambda-cyhalothrin was extensively but slowly absorbed (Tmax, 2.69 h). The oral bioavailability was found to be 67.37%. Significant differences in the kinetic parameters between nervous tissues and plasma was observed. The maximum concentrations in hypothalamus (Cmax, 24.12 microg g(-1)) and myenteric plexus (Cmax, 25.12 microg g(-1)) were about 1.5 times higher than in plasma (Cmax, 15.65 microg ml(-1)) and 1.3 times higher than in liver (Cmax, 18.42 microg ml(-1)). Nervous tissue accumulation of lambda-cyhalothrin was also reflected by the area under the concentration curve ratios of tissue/plasma (liver). The T1/2beta for lambda-cyhalothrin was significantly greater for the nerve tissues, including neuromuscular fibres, (range 12-26 and 15-34 h, after i.v. and oral doses) than for plasma (7.55 and 10.27 h, respectively).

Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

PubMed

Brun, Paola; Qesari, Marsela; Marconi, Peggy C; Kotsafti, Andromachi; Porzionato, Andrea; Macchi, Veronica; Schwendener, Reto A; Scarpa, Marco; Giron, Maria C; Palù, Giorgio; Calistri, Arianna; Castagliuolo, Ignazio

2018-01-01

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets.

Intrinsic ruminal innervation in ruminants of different feeding types

PubMed Central

Münnich, Juliane; Gäbel, Gotthold; Pfannkuche, Helga

2008-01-01

According to their feeding habits, ruminants can be classified as grazers, concentrate selectors and those of intermediate type. The different feeding types are reflected in distinct anatomical properties of the forestomachs. The present study was designed to investigate whether the intrinsic innervation patterns of the rumen (the main part of the forestomach) differ between intermediate types and grazers. Myenteric plexus preparations from the rumen of goats (intermediate type), fallow deer (intermediate type), cattle (grazer) and sheep (grazer) were analysed by immunohistochemical detection of the following antigens: Hu-protein (HuC/D), choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calbindin (CALB) and somatostatin (SOM). Myenteric ganglia of cattle contained 73 ± 6 neurons per ganglion, whereas the ganglia of sheep were significantly smaller (45 ± 18 neurons per ganglion). The ganglion density of the myenteric plexus was highest in fallow deer (15 ± 3 ganglia per cm2) and lowest in cattle (6 ± 1 ganglia per cm2). All myenteric neurons were either ChAT or NOS positive. The proportion of NOS-positive neurons was significantly lower in sheep (29.5 ± 8.2% of all neurons) than in goats (44.2 ± 9.8%). In all species, additional analysis of the different neuropeptides revealed the following subpopulations in descending order of percentile appearance: ChAT/SP > NOS/VIP/NPY > ChAT/– > NOS/NPY. Expression of CALB was detected in a minority of the ChAT-positive neurons in all species. Somatostatin immunoreactive somata were found only in preparations obtained from fallow deer and sheep. These data suggest that the rumen of grazers is under stronger cholinergic control than the rumen of species belonging to the intermediate type, although most subpopulations of neurons are present in all species. However, whether the strong mixing patterns of low quality roughage during digestion are enabled by the prominent excitatory input of the rumen of grazers requires elucidation in further studies. PMID:18657258

Interstitial cells of Cajal in chagasic megaesophagus.

PubMed

de Lima, Marcus Aurelho; Cabrine-Santos, Marlene; Tavares, Marcelo Garcia; Gerolin, Gustavo Pacheco; Lages-Silva, Eliane; Ramirez, Luis Eduardo

2008-08-01

Chagasic visceromegalies are the most important digestive manifestations of Chagas disease and are characterized by motor disorders and dilation of organs such as esophagus and colon. One of the theories raised to explain the physiopathogenesis of chagasic megas is the plexus theory. Recent studies have shown a reduction of interstitial cells of Cajal (ICCs) in the colon of chagasic patients. These cells are present throughout the gastrointestinal tract and are considered to be pacemaker cells, that is, they are responsible for coordinating peristalsis and for mediating nerve impulses. In view of the lack of studies on these cells in megaesophagus and the previous observation of a reduction of ICCs in chagasic megacolons, we compared the distribution of ICCs in the esophagus of chagasic and nonchagasic patients to contribute to a better understanding of the physiopathogenesis of this esophageal disease. Esophageal biopsy samples from 10 chagasic and 5 nonchagasic patients were used. Cells were identified with the anti-CD117 antibody. The number of ICCs was quantified in longitudinal and circular muscle layers and myenteric plexus. The results were analyzed statistically by comparison of means. An intense reduction in the number of ICCs was observed in muscle layers and in the myenteric plexus of patients with megaesophagus. We conclude that there is an intense reduction of ICCs in the esophagus of chagasic patients when compared to nonchagasic patients, a finding supporting the important role of these cells in gastrointestinal tract motility. A deficiency in these cells might be implied in the genesis of megaesophagus.

Macrophages associated with the intrinsic and extrinsic autonomic innervation of the rat gastrointestinal tract.

PubMed

Phillips, Robert J; Powley, Terry L

2012-07-02

Interactions between macrophages and the autonomic innervation of gastrointestinal (GI) tract smooth muscle have received little experimental attention. To better understand this relationship, immunohistochemistry was performed on GI whole mounts from rats at three ages. The phenotypes, morphologies, and distributions of gut macrophages are consistent with the cells performing extensive housekeeping functions in the smooth muscle layers. Specifically, a dense population of macrophages was located throughout the muscle wall where they were distributed among the muscle fibers and along the vasculature. Macrophages were also associated with ganglia and connectives of the myenteric plexus and with the sympathetic innervation. Additionally, these cells were in tight registration with the dendrites and axons of the myenteric neurons as well as the varicosities along the length of the sympathetic axons, suggestive of a contribution by the macrophages to the homeostasis of both synapses and contacts between the various elements of the enteric circuitry. Similarly, macrophages were involved in the presumed elimination of neuropathies as indicated by their association with dystrophic neurons and neurites which are located throughout the myenteric plexus and smooth muscle wall of aged rats. Importantly, the patterns of macrophage-neuron interactions in the gut paralleled the much more extensively characterized interactions of macrophages (i.e., microglia) and neurons in the CNS. The present observations in the PNS as well as extrapolations from homologous microglia in the CNS suggest that GI macrophages play significant roles in maintaining the nervous system of the gut in the face of wear and tear, disease, and aging. Copyright © 2012 Elsevier B.V. All rights reserved.

Action of substance P and interaction of calcitonin gene-related peptide and substance P on the cat antral circular muscle.

PubMed

Ouyang, A; Broussard, D L; Feng, H S

1998-10-16

The actions of substance P (SP) and calcitonin gene-related peptide (CGRP) and their interaction were examined in vitro in the feline antrum and colon. Circular muscle contraction was seen in the antrum to both peptides, but only to SP in the proximal colon. Antral contraction was enhanced when both peptides were given together. This interaction was inhibited by tetrodotoxin or atropine. SP acted at the antrum via a smooth muscle neurokinin receptor which is not a (NK)-1 receptor. SP binding was displaced by neurokinin A but not by the NK-1 receptor antagonist, CP-96345. The colonic response was inhibited by CP-96345. Immunohistochemistry revealed SP-like immunoreactivity (SP-LI) in fibers in the antral myenteric plexus and circular muscle, while CGRP-like immunoreactivity (CGRP-LI) was seen in the myenteric plexus only, without co-localization. These studies supported the hypothesis that SP acted via the NK-2 receptor at the feline circular muscle in the antrum to induce contraction and at the NK-1 receptor in the proximal colon. CGRP enhanced the effect of SP via a cholinergic pathway.

Achalasia—An Autoimmune Inflammatory Disease: A Cross-Sectional Study

PubMed Central

Furuzawa-Carballeda, J.; Aguilar-León, D.; Gamboa-Domínguez, A.; Valdovinos, M. A.; Nuñez-Álvarez, C.; Martín-del-Campo, L. A.; Enríquez, A. B.; Coss-Adame, E.; Svarch, A. E.; Flores-Nájera, A.; Villa-Baños, A.; Ceballos, J. C.; Torres-Villalobos, G.

2015-01-01

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection. PMID:26078981

Localization and Regulation of Fluorescence-Labeled Delta Opioid Receptor, Expressed in Enteric Neurons of Mice

PubMed Central

Scherrer, Gregory; Evans, Christopher J.; Kieffer, Brigitte L.; Bunnett, Nigel W.

2015-01-01

Background & Aims Opioids and opiates inhibit gastrointestinal functions via μ, δ, and κ receptors. Although agonists of the δ opioid receptor (DOR) suppress motility and secretion, little is known about the localization and regulation of DOR in the gastrointestinal tract. Methods We studied mice in which the gene that encodes the enhanced green fluorescent protein (eGFP) was inserted into Oprd1, which encodes DOR, to express an ~80 kDa product (DOReGFP). We used these mice to examine how agonists of DOR regulate the subcellular distribution of the DOR. Results DOReGFP was expressed in all regions but confined to enteric neurons and fibers within the muscularis externa. In the submucosal plexus, DOReGFP was detected in neuropeptide Y-positive secretomotor and vasodilator neurons of the small intestine, but was rarely observed in the large bowel. In the myenteric plexus of the small intestine, DOReGFP was present in similar proportions of excitatory motoneurons and interneurons that expressed choline acetyltransferase and substance P, and in inhibitory motoneurons and interneurons that contained nitric oxide synthase. DOReGFP was mostly present in nitrergic myenteric neurons of colon. DOReGFP and μ opioid receptors were often co-expressed. DOReGFP-expressing neurons were associated with enkephalin-containing varicosities and enkephalin-induced, clathrin- and dynamin-mediated endocytosis and lysosomal trafficking of DOReGFP. DOReGFP replenishment at the plasma membrane was slow, requiring de novo synthesis, rather than recycling. Conclusions DOR localizes specifically to submucosal and myenteric neurons, which might account for the ability of DOR agonists to inhibit gastrointestinal secretion and motility. Sustained down-regulation of DOReGFP at the plasma membrane of activated could induce long-lasting tolerance to DOR agonists. PMID:21699782

Neuropeptide Y in the guinea-pig biliary tract.

PubMed

Allen, J M; Gu, J; Adrian, T E; Polak, J M; Bloom, S R

1984-07-15

High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7 +/- 5.4 pmol/g), cystic duct (25.4 +/- 9.2 pmol/g) and common bile duct (54.7 +/- 11.5 pmol/g) of the guinea-pig using a recently developed radioimmunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.

Ultrastructural study of relationships between c-kit immunoreactive interstitial cells and other cellular elements in the human colon.

PubMed

Mazzia, C; Porcher, C; Julé, Y; Christen, M O; Henry, M

2000-05-01

C-kit immunocytochemistry was performed on ultrathin sections of human distal colon. Our attention was focused on relationships between c-kit immunoreactive interstitial cells (c-kit ICs) and muscular cells and nervous elements located in the external muscular layers of the colonic wall. C-kit ICs established membrane apposition with both nerve fibers and smooth muscle cells of, respectively, the longitudinal and circular muscle layers, the myenteric area, and the extremus submucosus plexus. C-kit ICs also surrounded the external submucosus plexus and established membrane appositions with nerve elements located inside the myenteric ganglia. These membrane appositions were observed either at the level of the c-kit IC bodies or at that of their cytoplasmic processes. In some cases, membrane appositions were observed concomitantly between the c-kit ICs, nerve fibers, and smooth muscle cells. In all the regions studied, the c-kit ICs were also found to be located in the close vicinity of blood vessels and to have established close contacts with non-immunoreactive fibroblast-like cells. The results of the present study shed essential light on the relationships of c-kit ICs with the neighboring muscle cells and nerve elements, and confirm that the intercalated c-kit ICs well fit with the so-called "interstitial cells of Cajal".

Mechanism of Activation of Enteric Nociceptive Neurons via Interaction of TLR4 and TRPV1 Receptors.

PubMed

Filippova, L V; Fedorova, A V; Nozdrachev, A D

2018-03-01

Evidence obtained by immunohistochemical double labeling and confocal laser scanning microscopy suggests that capsaicin, a ligand of the TRPV1 nociceptive vanilloid receptor, increases the number of TLR4-positive neurons in the rat colon myenteric plexus. In colitis caused by trinitrobenzene sulfonate, an increase in TRPV1 expression was more significant in both plexuses. Specific inhibitor of the TLR4 (C34) pattern-recognition receptor reduces TRPV1 expression in enteric neurons of both intact rats and rats with induced acute colitis. Thus, stimulation of nociceptive neurons by means of direct activation of their receptors of innate immunity (TLR4) is one of the possible mechanisms underlying the visceral pain in bacterial invasion and inflammatory bowel diseases.

[Focus on Achalasia].

PubMed

Guillaumot, Marie-Anne; Barret, Maximilien; Leblanc, Sarah; Leconte, Mahaut; Dousset, Bertrand; Oudjit, Ammar; Prat, Frédéric; Chaussade, Stanislas

2018-01-01

The pathophysiology of achalasia is largely unknown, and involves the destruction of ganglion cell in the esophageal myenteric plexus. High-resolution esophageal manometry is the key investigation. Endoscopic pneumodilatation and laparoscopic Heller myotomy have comparable short-term success rates, around 90%. The main complication after pneumodilatation is esophageal perforation, occurring in about 1% of cases. Peroral endoscopic myotomy is a promising treatment modality, however with frequent post-procedural gastroesophageal reflux. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine

PubMed Central

Ross, Ruth A; Brockie, Heather C; Fernando, Susanthi R; Saha, Bijali; Razdan, Raj K; Pertwee, Roger G

1998-01-01

We have investigated the nature of cannabinoid receptors in guinea-pig small intestine by establishing whether this tissue contains cannabinoid receptors with similar binding properties to those of brain CB1 receptors. The cannabinoids used were the CB1-selective antagonist SR141716A, the CB2-selective antagonist SR144528, the novel cannabinoid receptor ligand, 6′-azidohex-2′-yne-Δ8-tetrahydrocannabinol (O-1184), and the agonists CP55940, which binds equally well to CB1 and CB2 receptors, and WIN55212-2, which shows marginal CB2 selectivity.[3H]-CP55940 (1 nM) underwent extensive specific binding both to forebrain membranes (76.3%) and to membranes obtained by sucrose density gradient fractionation of homogenates of myenteric plexus-longitudinal muscle of guinea-pig small intestine (65.2%).Its binding capacity (Bmax) was higher in forebrain (4281 fmol mg−1) than in intestinal membranes (2092 fmol mg−1). However, the corresponding KD values were not significantly different from each other (2.29 and 1.75 nM respectively). Nor did the Ki values for its displacement by CP55940, WIN55212-2, O-1184, SR141716A and SR144528 from forebrain membranes (0.87, 4.15, 2.85, 5.32 and 371.9 respectively) differ significantly from the corresponding Ki values determined in experiments with intestinal membranes (0.99, 5.03, 3.16, 4.95 and 361.5 nM respectively).The Bmax values of [3H]-CP55940 and [3H]-SR141716A in forebrain membranes did not differ significantly from each other (4281 and 5658 fmol mg−1) but were both greater than the Bmax of [3H]-WIN55212-2 (2032 fmol mg−1).O-1184 (10 or 100 nM) produced parallel dextral shifts in the log concentration-response curves of WIN55212-2 and CP55940 for inhibition of electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation, its KD values being 0.20 nM (against WIN55212-2) and 0.89 nM (against CP55940).We conclude that cannabinoid binding sites in guinea-pig small intestine closely resemble CB1 binding sites of guinea-pig brain and that O-1184 behaves as a cannabinoid receptor antagonist in the guinea-pig myenteric plexus-longitudinal muscle preparation. PMID:9863666

Development of the intrinsic and extrinsic innervation of the gut.

PubMed

Uesaka, Toshihiro; Young, Heather M; Pachnis, Vassilis; Enomoto, Hideki

2016-09-15

The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract. Copyright © 2016 Elsevier Inc. All rights reserved.

How to approach the ENS: various ways to analyse motility disorders in situ and in vitro.

PubMed

Schäfer, K-H; Hagl, C I; Wink, E; Holland-Cunz, S; Klotz, M; Rauch, U; Waag, K-L

2003-06-01

Motility disorders of the human intestine are so variable that they cannot be diagnosed by just one technique. Their aetiology is obviously so varied that they have to be approached with a broad range of technical methods. These reach from the simple haematoxylin-stained section to the isolation of stem or precursor cells. In this study, various methods to investigate the enteric nervous system and its surrounding tissue are demonstrated. While sections from paraffin-embedded material or cryostat sections provide only a two-dimensional perspective of the ENS, the whole-mount method yields three-dimensional perspectives of large areas of the gut wall. The three-dimensional impression can even be enhanced by electron microscopy of the isolated ENS. Dynamical aspects of ENS development can be tackled by in vitro studies. The myenteric plexus can be isolated and cultivated under the influence of the microenvironment (protein extracts). Although the postnatal myenteric plexus is not fully developed, the choice of embryological neuronal cells seems to be more effective for certain approaches. They can be isolated from the embryonic mouse gut and cultivated under the influence of various factors. This method seems to us a valuable tool for the investigation of the aetiology of motility disorders, although only a "complete" approach which considers all available methods will yield at the end a clear understanding which might lead to new therapeutical concepts.

A qualitative and quantitative study on the enkephalinergic innervation of the pig gastrointestinal tract.

PubMed

Porcher, C; Julé, Y; Henry, M

2000-03-01

Enkephalins are involved in neural control of digestive functions such as motility, secretion, and absorption. To better understand their role in pigs, we analyzed the qualitative and quantitative distribution of enkephalin immunoreactivity (ENK-IR) in components of the intestinal wall from the esophagus to the anal sphincter. Immunohistochemical labelings were analyzed using conventional fluorescence and confocal microscopy. ENK-IR was compared with the synaptophysin immunoreactivity (SYN-IR). The results show that maximal ENK-IR levels in the entire digestive tract are reached in the myenteric plexuses and, to a lesser extent, in the external submucous plexus and the circular muscle layer. In the longitudinal muscle layer, ENK-IR was present in the esophagus, stomach, rectum, and anal sphincter, whereas it was absent from the duodenum to the distal colon. In the ENK-IR plexuses and muscle layers, more than 60% of the nerve fibers identified by SYN-IR expressed ENK-IR. No ENK-IR was observed in the internal submucous plexus and the mucosa; the latter was found to contain ENK-IR endocrine cells. These results strongly suggest that, in pigs, enkephalins play a major role in the regulatory mechanisms that underlie the neural control of digestive motility.

Enkephalin neurons in the guinea pig proximal colon: an immunocytochemical study using an antiserum to methionine-enkephalin-Arg6-Gly7-Leu8.

PubMed

Kobayashi, S; Suzuki, M; Yanaihara, N

1985-02-01

The distribution and structure of the neurons containing opioid peptide-like immunoreactivity (enkephalin neurons) in the antimesenteric border of the guinea pig proximal colon were immunocytochemically investigated using an antiserum for methionine-enkephalin-Arg6-Gly7-Leu8 (R-0171). Whole-mount preparations of the different layers of the intestine perfusion-fixed with Bouin's fluid were immunostained by peroxidase-antiperoxidase techniques. Immunopositive nerve fibers were apparent in the longitudinal muscle layer, myenteric plexus, circular muscle layer and submucosa. Immunopositive perikarya of the ganglionic cells were found in the myenteric plexus. A Golgi-type panoramic view was obtained in the intensely-immunostained enkephalin neurons. Distinct immunoreactivity was shown in the many Dogiel type 1 neurons, characterized by short broad processes (winglets or alulae) and one long axon-like process, as well as a few type 2, characterized by several tapering processes, and type 3 neurons, characterized by dendrite-like processes. Many twig-like processes originated from the free margin of the winglet of the enkephalin neurons (wing-ramuli). A part of them entered the intramuscular fasciculus, while the rest remained inside the ganglion. There were transitional forms between these wing-ramuli and the tapering processes of the type 2 neurons or the dendrite-like processes of the type 3 neurons. The axon-like processes sent out branches (axon-ramuli) along their courses or into the intramuscular fasciculus. At the origin of these axon-ramuli, there was a nodulous or humped swelling of the axon-like process (nodulus or crista). In the myenteric ganglion, the axon-ramuli formed varicose terminals. In the guinea pig proximal colon, many axon-like processes of the enkephalin neurons ran in the oral direction. This polarity of neuronic processes may have a functional significance in the neuronal control of the antiperistalsis.

In situ monitoring of myenteric neuron activity using acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors.

PubMed

Müntze, Gesche Mareike; Pouokam, Ervice; Steidle, Julia; Schäfer, Wladimir; Sasse, Alexander; Röth, Kai; Diener, Martin; Eickhoff, Martin

2016-03-15

The response characteristics of acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors (AcFETs) are quantitatively analyzed by means of a kinetic model. The characterization shows that the covalent enzyme immobilization process yields reproducible AcFET characteristics with a Michaelis constant KM of (122 ± 4) μM for the immobilized enzyme layer. The increase of KM by a factor of 2.4 during the first four measurement cycles is attributed to partial denaturation of the enzyme. The AcFETs were used to record the release of acetylcholine (ACh) by neuronal tissue cultivated on the gate area upon stimulation by rising the extracellular K(+) concentration. The neuronal tissue constituted of isolated myenteric neurons from four to 12 days old Wistar rats, or sections from the muscularis propria containing the myenteric plexus from adult rats. For both cases the AcFET response was demonstrated to be related to the activity of the immobilized acetylcholinesterase using the reversible acetylcholinesterase blocker donepezil. A concentration response curve of this blocking agent revealed a half maximal inhibitory concentration of 40 nM which is comparable to values measured by complementary in vitro methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

Bidirectional regulation of human colonic smooth muscle contractility by tachykinin NK(2) receptors.

PubMed

Nakamura, Akihiro; Tanaka, Takahiro; Imanishi, Akio; Kawamoto, Makiko; Toyoda, Masao; Mizojiri, Gaku; Tsukimi, Yasuhiro

2011-01-01

In this study, we attempted to clarify the mechanism of tachykinin-induced motor response in isolated smooth muscle preparations of the human colon. Fresh specimens of normal colon were obtained from patients suffering from colonic cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with circular direction was monitored isometrically. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) produced marked contraction. All of these contractions were inhibited by saredutant, a selective NK(2)-R antagonist, but not by CP122721, a selective NK(1)-R antagonist or talnetant, a selective NK(3)-R antagonist. βAla(8)-NKA(4-10) induced concentration-dependent contraction similar to NKA, but Sar(9)-Met(11)-SP and Met-Phe(7)-NKB did not cause marked contraction. Colonic contraction induced by βAla(8)-NKA(4-10) was completely blocked by saredutant, but not by atropine. Tetrodotoxin or N(G)-nitro-L-arginine methyl ester pretreatment significantly enhanced βAla(8)-NKA(4-10)-induced contraction. Immunohistochemical analysis showed that the NK(2)-R was expressed on the smooth muscle layers and myenteric plexus where it was also co-expressed with neuronal nitric oxide synthase in the myenteric plexus. These results suggest that the NK(2)-R is a major contributor to tachykinin-induced smooth muscle contraction in human colon and that the NK(2)-R-mediated response consists of an excitatory component via direct action on the smooth muscle and an inhibitory component possibly via nitric oxide neurons.

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs.

PubMed

Kojima, Yu; Fujii, Hisao; Katsui, Renta; Nakajima, Yoshiyuki; Takaki, Miyako

2006-10-01

The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT(4) receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT(4) receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of mosapride were mediated through endogenously active, intrinsic 5-HT(4) receptors which may be post-synaptically located in the myenteric plexus of the anorectum.

Moderate physical exercise protects myenteric metabolically more active neurons in mice infected with Trypanosoma cruzi.

PubMed

Moreira, Neide Martins; de Moraes, Solange Marta Franzói; Dalálio, M M O; Gomes, Mônica Lúcia; Sant'ana, D M G; de Araújo, Silvana Marques

2014-02-01

Trypanosoma cruzi causes neuronal myenteric depopulation compromising intestinal function. The purpose of this study was to evaluate the influence of moderate physical exercise on NADH diaphorase (NADH-d)-positive neurons in the myenteric plexus and intestinal wall of the colon in mice infected with T. cruzi. Forty 30-day-old male Swiss mice were divided into the following groups: trained infected (TI), sedentary infected (SI), trained control (TC), and sedentary control. The TC and TI groups were subjected to a moderate physical exercise program on a treadmill for 8 weeks. Three days after finishing physical exercise, the TI and SI groups were intraperitoneally inoculated with 1,300 blood trypomastigotes of the Y strain of Trypanosoma cruzi. Parasitemia was evaluated from days 4 to 61 after inoculation. On day 75 of infection, myenteric neurons in the colon were quantified (NADH-d), and inflammatory foci were counted. Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) levels were evaluated in plasma. The results were compared using analysis of variance and the Kruskal-Wallis test at a 5 % significance level. Moderate physical exercise reduced the parasite peak on day 8 of infection (p = 0.0132) and total parasitemia (p = 0.0307). It also prevented neuronal depopulation (p < 0.01), caused hypertrophy of these cells (p < 0.05), prevented the formation of inflammatory foci (p < 0.01), and increased the synthesis of TNF-α (p < 0.01) and TGF-β (p > 0.05). These results reinforce the therapeutic benefits of moderate physical exercise for T. cruzi infection.

Distribution of the P2X2 receptor and chemical coding in ileal enteric neurons of obese male mice (ob/ob)

PubMed Central

Mizuno, Márcia Sanae; Crisma, Amanda Rabello; Borelli, Primavera; Schäfer, Bárbara Tavares; Silveira, Mariana Póvoa; Castelucci, Patricia

2014-01-01

AIM: To investigate the colocalization, density and profile of neuronal areas of enteric neurons in the ileum of male obese mice. METHODS: The small intestinal samples of male mice in an obese group (OG) (C57BL/6J ob/ob) and a control group (CG) (+/+) were used. The tissues were analyzed using a double immunostaining technique for immunoreactivity (ir) of the P2X2 receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT) and calretinin (Calr). Also, we investigated the density and profile of neuronal areas of the NOS-, ChAT- and Calr-ir neurons in the myenteric plexus. Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method. RESULTS: The analysis demonstrated that the P2X2 receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG. Neuronal density values (neuron/cm2) decreased 31% (CG: 6579 ± 837; OG: 4556 ± 407) and 16.5% (CG: 7796 ± 528; OG: 6513 ± 610) in the NOS-ir and calretinin-ir neurons in the OG, respectively (P < 0.05). Density of ChAT-ir (CG: 6200 ± 310; OG: 8125 ± 749) neurons significantly increased 31% in the OG (P < 0.05). Neuron size studies demonstrated that NOS, ChAT, and Calr-ir neurons did not differ significantly between the CG and OG groups. The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG. CONCLUSION: Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir, ChAT-ir and CalR-ir myenteric neurons. PMID:25320527

Prolonged high fat diet ingestion, obesity, and type 2 diabetes symptoms correlate with phenotypic plasticity in myenteric neurons and nerve damage in the mouse duodenum

PubMed Central

Stenkamp-Strahm, Chloe M.; Nyavor, Yvonne E. A.; Kappmeyer, Adam J.; Horton, Sarah; Gericke, Martin; Balemba, Onesmo B.

2015-01-01

Symptoms of diabetic gastrointestinal dysmotility indicate neuropathy of the enteric nervous system. Long-standing diabetic enteric neuropathy has not been fully characterized, however. We used prolonged high fat diet ingestion (20 weeks) in a mouse model to mimic human obese and type 2 diabetic conditions, and analyzed changes seen in neurons of the duodenal myenteric plexus. Ganglionic and neuronal size, number of neurons per ganglionic area, density indices of neuronal phenotypes (immunoreactive nerve cell bodies and varicosities per ganglion or tissue area) and nerve injury were measured. Findings were compared with results previously seen in mice fed the same diet for 8 weeks. Compared to mice fed standard chow, those on a prolonged high fat diet had smaller ganglionic and cell soma areas. Myenteric VIP- and ChAT-immunoreactive density indices were also reduced. Myenteric nerve fibers were markedly swollen and cytoskeletal protein networks were disrupted. The number of nNOS nerve cell bodies per ganglia was increased, contrary to the reduction previously seen after 8 weeks, but the density index of nNOS varicosities was reduced. Mice fed high fat and standard chow diets experienced an age-related reduction in total neurons, biasing towards neurons of sensory phenotype. Meanwhile ageing was associated with an increase in excitatory neuronal markers. Collectively, these results support a notion that nerve damage underlies diabetic symptoms of dysmotility, and reveals adaptive ENS responses to the prolonged ingestion of a high fat diet. This highlights a need to mechanistically study long-term diet-induced nerve damage and age-related impacts on the ENS. PMID:25722087

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs

PubMed Central

Robinson, Ainsley M.; Miller, Sarah; Payne, Natalie; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

2015-01-01

Background & Aims The therapeutic benefits of mesenchymal stem cells (MSCs), such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal loss and damage associated with intestinal inflammation in the guinea-pig model of colitis. Methods At 3 hours after induction of colitis by 2,4,6-trinitrobenzene-sulfonate (TNBS), guinea-pigs received either human bone marrow-derived MSCs, conditioned medium (CM), or unconditioned medium by enema into the colon. Colon tissues were collected 6, 24 and 72 hours after administration of TNBS. Effects on body weight, gross morphological damage, immune cell infiltration and myenteric neurons were evaluated. RT-PCR, flow cytometry and antibody array kit were used to identify neurotrophic and neuroprotective factors released by MSCs. Results MSC and CM treatments prevented body weight loss, reduced infiltration of leukocytes into the colon wall and the myenteric plexus, facilitated repair of damaged tissue and nerve fibers, averted myenteric neuronal loss, as well as changes in neuronal subpopulations. The neuroprotective effects of MSC and CM treatments were observed as early as 24 hours after induction of inflammation even though the inflammatory reaction at the level of the myenteric ganglia had not completely subsided. Substantial number of neurotrophic and neuroprotective factors released by MSCs was identified in their secretome. Conclusion MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti-inflammatory effects. PMID:26397368

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

PubMed Central

Wang, Jian; Mou, Yaru; Zhang, Qiangye; Zhang, Fan; Yang, Hongchao; Zhang, Wentong; Li, Aiwu

2013-01-01

Purpose The aim of this study was to investigate the expression and significance of neuroligins in myenteric cells of Cajal (ICC-MY) in Hirschsprung’s disease (HSCR). Methods Longitudinal muscle with adherent myenteric plexus (LMMP) from surgical excision waste colon of HSCR children were prepared by peeling off the mucous layer, sub-mucosal layer and circular muscle. Neuroligins, c-Kit (c-Kit-immunoreactivity representing ICC) and their relationship were assessed by double labeling immunofluorescence staining. ICC-MY were dissociated and cultured from LMMP by enzymolysis method, and were purified and analyzed using a combination of magnetic-activated cell sorting (MACS) and flow cytometry (FCM). Western-blot analysis was applied to compare and evaluate the expression levels of neuroligins in ICC-MY which were dissociated from different segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Results Neuroligins and c-Kit were expressed on the same cells (ICC-MY); ICC-MY were dissociated, cultured and purified. For HSCR, neuroligins were expressed significantly in ICC-MY from ganglionic colonic segments, moderately in those from transitional colonic segments and down-regulated significantly in those from aganglionic colonic segments. Conclusions Neuroligins were expressed in ICC-MY of human beings, and the expression varies from different segments of HSCR. This abnormal expression might play an important role in the pathogenesis of this disease through affecting the synaptic function of ICC-MY. PMID:23840625

Topical application of benzalkonium chloride to the stomach serosa increases gastric emptying time, acid secretion, serum gastrin and size of the mucosa.

PubMed

Zucoloto, S; Romanello, L M F; Garcia, S B; Sobreira, L F R; Barbosa, A J A; Troncon, L E A

2002-11-01

In the present study we evaluated the effects of gastric myenteric denervation using benzalkonium chloride (BAC) on the time for gastric emptying, as well as gastric secretion, and mucosal epithelial cell size and population in rats. Wistar rats were treated with topical serosal application of BAC to the stomach. Control animals received saline. Ninety days after surgery, gastric emptying time, gastric acid secretion and serum gastrin levels were studied. Next, the animals were sacrificed and the stomachs were removed, fixed in formalin and histologically processed for histomorphometry of the height, area and volume of the glandular portion, and volume and population of mucous, chief, parietal, G- and labelled cells. BAC animals showed a significant delay in gastric emptying and an increase in gastric acid secretion and serum gastrin levels. These animals also presented a significant reduction of myenteric neuron number, hypertrophy of parietal and chief cells, hyperplasia of G cells and an increase in the gastric mucosa area. The absence of the myenteric plexus seems to protect the stomach from the hyperplastic effects of hypergastrinemia. Gastric food stasis may act as a factor triggering morphological and functional alterations of the gastric epithelium. Although gastric food stasis is a common finding in medical practice, its physiopathological consequences are poorly understood and have not been frequently discussed in the literature.

Self-administration of methamphetamine alters gut biomarkers of toxicity

PubMed Central

Flack, Amanda; Persons, Amanda L.; Kousik, Sharanya M.; Napier, T. Celeste; Moszczynska, Anna

2018-01-01

Methamphetamine (METH) is a highly abused psychostimulant that is associated with an increased risk for developing Parkinson’s disease (PD). This enhanced vulnerability likely relates to the toxic effects of METH that overlap with PD pathology, for example, aberrant functioning of α-synuclein and parkin. In PD, peripheral factors are thought to contribute to central nervous system (CNS) degeneration. For example, α-synuclein levels in the enteric nervous system (ENS) are elevated, and this precedes the onset of motor symptoms. It remains unclear whether neurons of the ENS, particularly catecholaminergic neurons, exhibit signs of METH-induced toxicity as seen in the CNS. The aim of this study was to determine whether self-administered METH altered the levels of α-synuclein, parkin, tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DβH) in the myenteric plexus of the distal colon ENS. Young adult male Sprague-Dawley rats self-administered METH for 3 h per day for 14 days and controls were saline-yoked. Distal colon tissue was collected at 1, 14, or 56 days after the last operant session. Levels of α-synuclein were increased, while levels of parkin, TH, and DβH were decreased in the myenteric plexus in the METH-exposed rats at 1 day following the last operant session and returned to the control levels after 14 or 56 days of forced abstinence. The changes were not confined to neurofilament-positive neurons. These results suggest that colon biomarkers may provide early indications of METH-induced neurotoxicity, particularly in young chronic METH users who may be more susceptible to progression to PD later in life. PMID:28661099

Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon.

PubMed

Matsumoto, Kenjiro; Kurosawa, Emi; Terui, Hiroyuki; Hosoya, Takuji; Tashima, Kimihito; Murayama, Toshihiko; Priestley, John V; Horie, Syunji

2009-08-01

We investigated immunohistochemical differences in the distribution of TRPV1 channels and the contractile effects of capsaicin on smooth muscle in the mouse rectum and distal, transverse, and proximal colon. In the immunohistochemical study, TRPV1 immunoreactivity was found in the mucosa, submucosal, and muscle layers and myenteric plexus. Large numbers of TRPV1-immunoreactive axons were observed in the rectum and distal colon. In contrast, TRPV1-positive axons were sparsely distributed in the transverse and proximal colon. The density of TRPV1-immunoreactive axons in the rectum and distal colon was much higher than those in the transverse and proximal colon. Axons double labeled with TRPV1 and protein gene product (PGP) 9.5 were detected in the myenteric plexus, but PGP 9.5-immunoreactive cell bodies did not colocalize with TRPV1. In motor function studies, capsaicin induced a fast transient contraction, followed by a large long-lasting contraction in the rectum and distal colon, whereas in the transverse and proximal colon only the transient contraction was observed. The capsaicin-induced transient contraction from the proximal colon to the rectum was moderately inhibited by an NK1 or NK2 receptor antagonist. The capsaicin-induced long-lasting contraction in the rectum and distal colon was markedly inhibited by an NK2 antagonist, but not by an NK1 antagonist. The present results suggest that TRPV1 channels located on the rectum and distal colon play a major role in the motor function in the large intestine.

Potency of three opiate antagonists to reverse the inhibitory activity of dynorphin, enkephalins and opioid-like alkaloids on the guinea pig ileum.

PubMed

Yoshimura, K; Huidobro-Toro, J P; Way, E L

1982-10-15

To test the hypothesis that dynorphin is a K-opiate agonist acting on the myenteric plexus, the potency of two benzomorphan antagonists (Win 44, 441 and Mr 2266) to block the inhibitory action of dynorphin, enkephalins and opioid alkaloids was determined on the longitudinal muscle preparation of the guinea pig ileum. The effectiveness of these antagonists was compared to that of naloxone. Antagonistic potency was established by calculating the apparent antagonist dissociation constant, Ke, as derived from Schild plots. Win 44, 441 and Mr 2266 were about 7-8 times more potent than naloxone against dynorphin, dynorphin-(1-13) or ethylketocyclazocine. Although the Ke obtained with Win 44, 441 or Mr 2266 against dynorphin or ethylketocyclazocine were significantly lower than those of naloxone, the values obtained for these antagonists did not differ significantly in the case of each of these agonists. With respect to the antagonism of the enkephalins or normorphine, Win 44, 441 was the most potent antagonist. Its Ke value for the enkephalins was 2.5-3 times lower than those for dynorphin or ethylketocyclazocine and in comparison to naloxone, Win 44, 441 was about 5 times more potent. Although Mr 2266 was a potent antagonist of dynorphin, ethylketocyclazocine, the enkephalins or normorphine, it showed no selectivity of action. The fact that the 3 opiate antagonists evidenced similar Ke values for dynorphin and ethylketocyclazocine, but different ones for the enkephalins or normorphine supports the conclusion that dynorphin activates preferentially K- but not mu-opiate receptors in the myenteric plexus.

Expression of Vesicular Glutamate Transporters Type 1 and 2 in Sensory and Autonomic Neurons Innervating the Mouse Colorectum

PubMed Central

Brumovsky, Pablo R.; Robinson, David R.; La, Jun-Ho; Seroogy, Kim B.; Lundgren, Kerstin H.; Albers, Kathryn M.; Kiyatkin, Michael E.; Seal, Rebecca P.; Edwards, Robert H.; Watanabe, Masahiko; Hökfelt, Tomas; Gebhart, G.F.

2013-01-01

Vesicular glutamate transporters (VGLUTs) have been extensively studied in various neuronal systems, but their expression in visceral sensory and autonomic neurons remains to be analyzed in detail. Here we studied VGLUTs type 1 and 2 (VGLUT1 and VGLUT2, respectively) in neurons innervating the mouse colorectum. Lumbosacral and thoracolumbar dorsal root ganglion (DRG), lumbar sympathetic chain (LSC), and major pelvic ganglion (MPG) neurons innervating the colorectum of BALB/C mice were retrogradely traced with Fast Blue, dissected, and processed for immunohistochemistry. Tissue from additional naïve mice was included. Previously characterized antibodies against VGLUT1, VGLUT2, and calcitonin gene-related peptide (CGRP) were used. Riboprobe in situ hybridization, using probes against VGLUT1 and VGLUT2, was also performed. Most colorectal DRG neurons expressed VGLUT2 and often colocalized with CGRP. A smaller percentage of neurons expressed VGLUT1. VGLUT2-immunoreactive (IR) neurons in the MPG were rare. Abundant VGLUT2-IR nerves were detected in all layers of the colorectum; VGLUT1-IR nerves were sparse. A subpopulation of myenteric plexus neurons expressed VGLUT2 protein and mRNA, but VGLUT1 mRNA was undetectable. In conclusion, we show 1) that most colorectal DRG neurons express VGLUT2, and to a lesser extent, VGLUT1; 2) abundance of VGLUT2-IR fibers innervating colorectum; and 3) a subpopulation of myenteric plexus neurons expressing VGLUT2. Altogether, our data suggests a role for VGLUT2 in colorectal glutamatergic neurotransmission, potentially influencing colorectal sensitivity and motility. PMID:21800314

Sigma receptor ligand N,N'-di-(ortho-tolyl)guanidine inhibits release of acetylcholine in the guinea pig ileum.

PubMed

Cambell, B G; Keana, J F; Weber, E

1991-11-26

The inhibition of stimulated contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation by sigma receptor ligands has been previously described. In this study, the stimulated release of [3H]acetylcholine from cholinergic nerve terminals in this same preparation was monitored in the presence and absence of sigma receptor ligands. N,N'-Di-(orthotolyl)guanidine (DTG) and other compounds selective for the sigma receptor inhibited stimulated [3H]acetylcholine release. These results suggest that their inhibition of stimulated contractions in this preparation was mediated by inhibition of acetylcholine release.

Architecture and Chemical Coding of the Inner and Outer Submucous Plexus in the Colon of Piglets

PubMed Central

Petto, Carola; Gäbel, Gotthold; Pfannkuche, Helga

2015-01-01

In the porcine colon, the submucous plexus is divided into an inner submucous plexus (ISP) on the epithelial side and an outer submucous plexus (OSP) on the circular muscle side. Although both plexuses are probably involved in the regulation of epithelial functions, they might differ in function and neurochemical coding according to their localization. Therefore, we examined expression and co-localization of different neurotransmitters and neuronal markers in both plexuses as well as in neuronal fibres. Immunohistochemical staining was performed on wholemount preparations of ISP and OSP and on cryostat sections. Antibodies against choline acetyltransferase (ChAT), substance P (SP), somatostatin (SOM), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and the pan-neuronal markers Hu C/D and neuron specific enolase (NSE) were used. The ISP contained 1,380 ± 131 ganglia per cm2 and 122 ± 12 neurons per ganglion. In contrast, the OSP showed a wider meshwork (215 ± 33 ganglia per cm2) and smaller ganglia (57 ± 3 neurons per ganglion). In the ISP, 42% of all neurons expressed ChAT. About 66% of ChAT-positive neurons co-localized SP. A small number of ISP neurons expressed SOM. Chemical coding in the OSP was more complex. Besides the ChAT/±SP subpopulation (32% of all neurons), a nNOS-immunoreactive population (31%) was detected. Most nitrergic neurons were only immunoreactive for nNOS; 10% co-localized with VIP. A small subpopulation of OSP neurons was immunoreactive for ChAT/nNOS/±VIP. All types of neurotransmitters found in the ISP or OSP were also detected in neuronal fibres within the mucosa. We suppose that the cholinergic population in the ISP is involved in the control of epithelial functions. Regarding neurochemical coding, the OSP shares some similarities with the myenteric plexus. Because of its location and neurochemical characteristics, the OSP may be involved in controlling both the mucosa and circular muscle. PMID:26230272

Stress increases descending inhibition in mouse and human colon.

PubMed

Reed, D E; Zhang, Y; Beyak, M J; Lourenssen, S; Blennerhassett, M G; Paterson, W G; Vanner, S J

2016-04-01

A relationship between stress and the symptoms of irritable bowel syndrome (IBS) has been well established but the cellular mechanisms are poorly understood. Therefore, we investigated effects of stress and stress hormones on colonic descending inhibition and transit in mouse models and human tissues. Stress was applied using water avoidance stress (WAS) in the animal model or mimicked using stress hormones, adrenaline (5 nM), and corticosterone (1 μM). Intracellular recordings were obtained from colonic circular smooth muscle cells in isolated smooth muscle/myenteric plexus preparations and the inhibitory junction potential (IJP) was elicited by nerve stimulation or balloon distension oral to the site of recording. Water avoidance stress increased the number of fecal pellets compared to control (p < 0.05). WAS also caused a significant increase in IJP amplitude following balloon distension. Stress hormones also increased the IJP amplitude following nerve stimulation and balloon distension (p < 0.05) in control mice but had no effect in colons from stressed mice. No differences were observed with application of ATP between stress and control tissues, suggesting the actions of stress hormones were presynaptic. Stress hormones had a large effect in the nerve stimulated IJP in human colon (increased >50%). Immunohistochemical studies identified alpha and beta adrenergic receptor immunoreactivity on myenteric neurons in human colon. These studies suggest that WAS and stress hormones can signal via myenteric neurons to increase inhibitory neuromuscular transmission. This could lead to greater descending relaxation, decreased transit time, and subsequent diarrhea. © 2016 John Wiley & Sons Ltd.

Effect of fumonisin-containing diet on the myenteric plexus of the jejunum in rats.

PubMed

Sousa, Fernando Carlos; Schamber, Christiano Rodrigues; Amorin, Sandra Sheila Seron; Natali, Maria Raquel Marçal

2014-10-01

Fumonisins are mycotoxins that naturally occur as contaminants in grains that are destined for animal and human consumption. These mycotoxins cause hepatotoxic, nephrotoxic, carcinogenic, teratogenic, immunotoxic, and neurotoxic effects in different intensities based on dose, time of exposure, and animal species. In the present study, male Wistar rats were fed between postnatal days 21 and 63 with diets that contained fumonisins B1+B2 at concentrations of 1 and 3mg/kg. The objective of the present study was to evaluate the effects of fumonisins on food intake, growth, weight gain, serum activity of the alanine aminotransferase and aspartate aminotransferase enzymes, and quantitative and morphometric parameters of myenteric neurons in the jejunum that are immunoreactive to HuC/D protein and neuronal nitric oxide synthase enzyme (nNOS). Diets that contained fumonisins did not significantly alter food intake or body and blood parameters. We did not observe significant differences in the neuronal density and proportion of nitrergic neurons but found a significant reduction of cell body areas in both neuronal populations. This study is the first to report the effects of fumonisins in the enteric nervous system. The possible mechanisms by which fumonisins impair neuronal development and the use of the enteric nervous system as a tool for the study of the neurotoxic effects of fumonisins are discussed. In conclusion, fumonisin-containing food negatively affected the growth of myenteric neurons. Copyright © 2014 Elsevier B.V. All rights reserved.

Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease

PubMed Central

Moses, P L; Ellis, L M; Anees, M R; Ho, W; Rothstein, R I; Meddings, J B; Sharkey, K A; Mawe, G M

2003-01-01

Background and aims: The precise aetiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. We screened sera from patients with achalasia or gastro-oesophageal reflux disease (GORD) to test for circulating antimyenteric neuronal antibodies. Methods: Serum was obtained from 45 individuals with achalasia, 16 with GORD, and 22 normal controls. Serum was used in immunohistochemistry to label whole mount preparations of ileum and oesophagus of the guinea pig and mouse. Also, sections of superior cervical and dorsal root ganglia, and spinal cord were examined. Results: Positive immunostaining of the myenteric plexus was detected in significantly more achalasia and GORD samples than control samples (achalasia, p<0.001; GORD, p<0.01), and immunoreactivity was significantly more intense with achalasia and GORD serum samples than controls (achalasia, p<0.01; GORD, p<0.05). There was no correlation between intensity of immunoreactivity and duration of achalasia symptoms. In most cases, achalasia and GORD sera stained all ileal submucosal and myenteric neurones, and oesophageal neurones. Immunostaining was not species specific; however, immunostaining was largely specific for enteric neurones. Western blot analysis failed to reveal specific myenteric neuronal proteins that were labelled by antibodies in achalasia or GORD serum. Conclusions: These data suggest that antineuronal antibodies are generated in response to tissue damage or some other secondary phenomenon in achalasia and GORD. We conclude that antineuronal antibodies found in the serum of patients with achalasia represent an epiphenomenon and not a causative factor. PMID:12692044

Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS

PubMed Central

Scarpa, Melania; Marchiori, Chiara; Sarasin, Gloria; Caputi, Valentina; Porzionato, Andrea; Giron, Maria Cecilia; Palù, Giorgio; Castagliuolo, Ignazio

2017-01-01

Background We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. Methods Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4. Results S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins. Conclusions S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome. PMID:28732069

Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS.

PubMed

Brun, Paola; Scarpa, Melania; Marchiori, Chiara; Sarasin, Gloria; Caputi, Valentina; Porzionato, Andrea; Giron, Maria Cecilia; Palù, Giorgio; Castagliuolo, Ignazio

2017-01-01

We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4. S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins. S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome.

Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes.

PubMed Central

Guard, S.; Watson, S. P.; Maggio, J. E.; Too, H. P.; Watling, K. J.

1990-01-01

1. The binding properties and pharmacological specificity of the selective NK3 tachykinin receptor agonist [3H))-senktide [( 3H]-succinyl[Asp6,MePhe8] substance P (6-11] have been examined in homogenates of guinea-pig ileum longitudinal muscle-myenteric plexus (LM/MP) and cerebral cortex. 2. Scatchard analysis of saturation binding studies in guinea-pig ileum LM/MP and cerebral cortex membranes indicated that [3H]-senktide bound to a single site with apparent high affinity, KD = 2.21 +/- 0.65 nM; Bmax = 13.49 +/- 0.04 fmol mg-1 protein in ileum and KD = 8.52 +/- 0.45 nM; Bmax = 76.3 +/- 1.6 fmol mg-1 protein in cortex (values are means +/- ranges; n = 2). 3. The pharmacological profile for tachykinins and analogues in displacing [3H]-senktide from ileum membranes was: [MePhe7] neurokinin B greater than neurokinin B (NKB) congruent to senktide greater than eledoisin greater than substance P (SP) greater than neurokinin A(NKA) greater than physalaemin greater than [Sar9,Met(O2)11]SP greater than [Nle10]NKA(4-10) = [Glp6,L-Pro9]-SP(6-11) greater than substance P methyl ester, consistent with [3H]-senktide binding to an NK3 subtype of tachykinin receptor. A similar rank order of affinity was obtained for these peptides in displacing [3H]-senktide from cortex membranes. 4. Several tachykinin receptor agonists were tested for their ability to displace [3H]-senktide from ileal and cortical NK3 binding sites and were found to be either weak displacers (pIC50 less than 5.00) or inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1694464

Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9

PubMed Central

Kubota, Kunitsugu; Ohtake, Nobuhiro; Ohbuchi, Katsuya; Mase, Akihito; Imamura, Sachiko; Sudo, Yuka; Miyano, Kanako; Yamamoto, Masahiro; Kono, Toru

2015-01-01

Various colonic motor activities are thought to mediate propulsion and mixing/absorption of colonic content. The Japanese traditional medicine daikenchuto (TU-100), which is widely used for postoperative ileus in Japan, accelerates colonic emptying in healthy humans. Hydroxy-α sanshool (HAS), a readily absorbable active ingredient of TU-100 and a KCNK3/KCNK9/KCNK18 blocker as well as TRPV1/TRPA1 agonist, has been investigated for its effects on colonic motility. Motility was evaluated by intraluminal pressure and video imaging of rat proximal colons in an organ bath. Distribution of KCNKs was investigated by RT-PCR, in situ hybridization, and immunohistochemistry. Current and membrane potential were evaluated with use of recombinant KCNK3- or KCNK9-expressing Xenopus oocytes and Chinese hamster ovary cells. Defecation frequency in rats was measured. HAS dose dependently induced strong propulsive “squeezing” motility, presumably as long-distance contraction (LDC). TRPV1/TRPA1 agonists induced different motility patterns. The effect of HAS was unaltered by TRPV1/TRPA1 antagonists and desensitization. Lidocaine (a nonselective KCNK blocker) and hydroxy-β sanshool (a geometrical isomer of HAS and KCNK3 blocker) also induced colonic motility as a rhythmic propagating ripple (RPR) and a LDC-like motion, respectively. HAS-induced “LDC,” but not lidocaine-induced “RPR,” was abrogated by a neuroleptic agent tetrodotoxin. KCNK3 and KCNK9 were located mainly in longitudinal smooth muscle cells and in neural cells in the myenteric plexus, respectively. Administration of HAS or TU-100 increased defecation frequency in normal and laparotomy rats. HAS may evoke strong LDC possibly via blockage of the neural KCNK9 channel in the colonic myenteric plexus. PMID:25634809

Histogenesis and prognostic value of myenteric spread in colorectal cancer: a Japanese multi-institutional study.

PubMed

Ueno, Hideki; Shirouzu, Kazuo; Shimazaki, Hideyuki; Kawachi, Hiroshi; Eishi, Yoshinobu; Ajioka, Yoichi; Okuno, Kiyotaka; Yamada, Kazutaka; Sato, Toshihiko; Kusumi, Takaya; Kushima, Ryoji; Ikegami, Masahiro; Kojima, Motohiro; Ochiai, Atsushi; Murata, Akihiko; Akagi, Yoshito; Nakamura, Takahiro; Sugihara, Kenichi

2014-03-01

The histogenesis of the pattern of cancer spread along Auerbach's plexus (myenteric spread: MS) remains unclear and its prognostic value in colorectal cancer (CRC) has not been thoroughly investigated. Pathology slides of 2845 pT2/pT3/pT4 CRCs stained with hematoxylin-eosin (H&E) were reviewed at 10 institutions. MS was classified into 2 groups depending on whether it was accompanied by the finding of perineural invasion (PN) within the lesion. In addition, immunohistochemical staining (D2-40, S100, CD56, synaptophysin) was performed for serially sectioned specimens from 50 CRCs diagnosed as having PN-negative MS. MS was observed in 504 patients (17.7 %); 360 patients were classified as having PN-positive MS and 144 as having PN-negative MS. The 5-year disease-free survival rate of patients with MS was lower than that of patients without MS (63.3 vs 82.7 %, P < 0.0001); however, there was no significant difference in survival outcome according to the presence or absence of intralesion PN in MS. Multivariate analysis showed that the prognostic impact of MS was independent of conventional prognosticators including T and N stages, vascular invasion and extramural PN. In all the tumors having PN-negative MS, remnants of neural tissue were identified within or around cancer nests located at the leading edge of MS. MS is an important prognostic factor for CRC. This feature is the result of cancer development with replacement of Auerbach's plexus and can be classified as intramural PN. The clinical significance of "Pn1" in the UICC/AJCC TNM classification could be enhanced by individual assessment both intramurally and extramurally.

Changes in enkephalin immunoreactivity of sympathetic ganglia and digestive tract of the cat after splanchnic nerve ligation.

PubMed

Bagnol, D; Herbrecht, F; Julé, Y; Jarry, T; Cupo, A

1993-09-22

The aim of the present study was to analyze changes in the enkephalin immunoreactivity of sympathetic prevertebral ganglia coeliac plexus and inferior mesenteric ganglion) and intestinal tract (myenteric plexus and external muscle layers) in cats 2 days after left thoracic splanchnic nerve ligation, using radioimmunoassay and immunohistochemical techniques. Specific polyclonal antibodies directed against methionine- and leucine-enkephalin were used. The nerve ligation led to a considerable increase in the enkephalin immunoreactivity in the cranial part of the ligated nerves. This finding confirms the presence, in the cat, of an enkephalin output originating from thoracic spinal structures which are probably enkephalin-containing preganglionic neurons. In prevertebral ganglia the nerve ligation induced a marked decrease in the enkephalin immunoreactivity, which was probably due to the interruption of thoracic enkephalin efferents projecting towards both the coeliac plexus and the inferior mesenteric ganglion. In the digestive tract, the nerve ligation depressed the methionine-enkephalin immunoreactivity only in the gastro-duodenal region, and had no effect on the ileo-colonic region. The results of the present study add to the growing evidence that the sympathetic nervous system is involved in regulating the enteric enkephalinergic innervation, which is probably involved in controlling the intestinal motility.

R-Type Ca2+ channels couple to inhibitory neurotransmission to the longitudinal muscle in the guinea-pig ileum.

PubMed

Rodriguez-Tapia, Eileen S; Naidoo, Vinogran; DeVries, Matthew; Perez-Medina, Alberto; Galligan, James J

2017-03-01

What is the central question of this study? Subtypes of enteric neurons are coded by the neurotransmitters they synthesize, but it is not known whether enteric neuron subtypes might also be coded by other proteins, including calcium channel subtypes controlling neurotransmitter release. What is the main finding and its importance? Our data indicate that guinea-pig ileum myenteric neuron subtypes may be coded by calcium channel subtypes. We found that R-type calcium channels are expressed by inhibitory but not excitatory longitudinal muscle motoneurons. R-Type calcium channels are also not expressed by circular muscle inhibitory motoneurons. Calcium channel subtype-selective antagonists could be used to target subtypes of neurons to treat gastrointestinal motility disorders. There is evidence that R-type Ca 2+ channels contribute to synaptic transmission in the myenteric plexus. It is unknown whether R-type Ca 2+ channels contribute to neuromuscular transmission. We measured the effects of the nitric oxide synthase inhibitor nitro-l-arginine (NLA), Ca 2+ channel blockers and apamin (SK channel blocker) on neurogenic relaxations and contractions of the guinea-pig ileum longitudinal muscle-myenteric plexus (LMMP) in vitro. We used intracellular recordings to measure inhibitory junction potentials. Immunohistochemical techniques localized R-type Ca 2+ channel protein in the LMMP and circular muscle. Cadmium chloride (pan-Ca 2+ channel blocker) blocked and NLA and NiCl 2 (R-type Ca 2+ channel blocker) reduced neurogenic relaxations in a non-additive manner. Nickel chloride did not alter neurogenic cholinergic contractions, but it potentiated neurogenic non-cholinergic contractions. Relaxations were inhibited by apamin, NiCl 2 and NLA and were blocked by combined application of these drugs. Relaxations were reduced by NiCl 2 or ω-conotoxin (N-type Ca 2+ channel blocker) and were blocked by combined application of these drugs. Longitudinal muscle inhibitory junction potentials were inhibited by NiCl 2 but not MRS 2179 (P2Y 1 receptor antagonist). Circular muscle inhibitory junction potentials were blocked by apamin, MRS 2179, ω-conotoxin and CdCl 2 but not NiCl 2 . We conclude that neuronal R-type Ca 2+ channels contribute to inhibitory neurotransmission to longitudinal muscle but less so or not all in the circular muscle of the guinea-pig ileum. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Methadone Management of Withdrawal Associated With Loperamide-related Opioid Use Disorder.

PubMed

Leo, Raphael J; Ghazi, Muhammad A; Jaziri, Kelly S

: Loperamide hydrochloride is an over-the-counter anti-diarrheal agent, acting via mu-opioid receptor agonist effects in the intestinal myenteric plexus. Although preclinical investigations suggested that abuse liability associated with loperamide use is low, there are increasing numbers of cases reported to the US Food and Drug Administration, of abuse, dependence, and withdrawal associated with loperamide use. A case of a patient with opioid use disorder, that is, in the form of protracted loperamide excess use, requiring management of withdrawal with methadone is presented. Management of withdrawal from abrupt loperamide discontinuation has not been discussed in the literature. Long-term treatment issues are also described.

The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

PubMed

Henry, M; Porcher, C; Julé, Y

1998-06-10

The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.

PubMed

Nogueira-Paiva, Nívia Carolina; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Diniz, Lívia Figueiredo; Caldas, Ivo Santana; Moura, Sandra Aparecida Lima de; Veloso, Vanja Maria; Guedes, Paulo Marcos da Matta; Tafuri, Washington Luiz; Bahia, Maria Terezinha; Carneiro, Cláudia Martins

2014-02-01

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Endocannabinoids as physiological regulators of colonic propulsion in mice.

PubMed

Pinto, Luisa; Izzo, Angelo A; Cascio, Maria Grazia; Bisogno, Tiziana; Hospodar-Scott, Karen; Brown, David R; Mascolo, Nicola; Di Marzo, Vincenzo; Capasso, Francesco

2002-07-01

Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo. Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography-mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry. Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus. We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.

Neuropeptide-hydrolysing activities in synaptosomal fractions from dog ileum myenteric, deep muscular and submucous plexi. Their participation in neurotensin inactivation.

PubMed

Barelli, H; Ahmad, S; Kostka, P; Fox, J A; Daniel, E E; Vincent, J P; Checler, F

1989-01-01

The mapping of neuropeptidases in synaptosomal fractions prepared from dog ileum myenteric, deep muscular and submucous plexus was established by means of fluorigenic substrates and specific inhibitors. Endopeptidase 24.11, angiotensin-converting enzyme and aminopeptidases were found in all tissues, the highest amounts being recovered in the submucous preparation. Post-proline dipeptidyl aminopeptidase was obtained in high quantities whatever the tissue source while proline endopeptidase was detected in low amounts and pyroglutamyl-peptide hydrolase was never detectable. The above peptidases were examined for their putative participation in the inactivation of neurotensin by monitoring the effect of specific inhibitors on the formation of the metabolites of labeled neurotensin separated by HPLC. Endopeptidases 24.11, 24.15 and 24.16 were respectively responsible for the formation of neurotensin(1-11), neurotensin(1-8) and neurotensin(1-10) that are devoid of biological activity. The secondary attacks occurring on neurotensin degradation products were the following: cleavage of neurotensin(1-10) into neurotensin(1-8) by angiotensin-converting enzyme; conversion of neurotensin(9-13) into neurotensin(11-13) by post-proline dipeptidyl aminopeptidase; hydrolysis of neurotensin(11-13) into free tyrosine by aminopeptidase(s).

Segmental dilatation of sigmoid colon in a neonate: atypical presentation and histology.

PubMed

Mahadevaiah, Shubha Attibele; Panjwani, Poonam; Kini, Usha; Mohanty, Suravi; Das, Kanishka

2011-03-01

Segmental dilatation of the colon is a rare disorder of colonic motility in children, often presenting with severe constipation in older infants, children, and occasionally adults. It may mimic the commoner Hirschsprung disease clinicoradiologically but differs in that the ganglion cell morphology and distribution are typically normal in the colon. We report a neonate with segmental dilatation of the sigmoid colon who had an atypical clinical presentation and describe certain abnormalities in bowel histology (hypertrophied muscularis propria, nerve plexus, and ganglion cells located within the circular layer rather than the normal myenteric location), for the first time in the English literature. Copyright © 2011 Elsevier Inc. All rights reserved.

Distribution and morphological characteristics of the interstitial cells of Cajal in the ileocaecal junction of the guinea-pig.

PubMed

Miyamoto-Kikuta, Sachiko; Ezaki, Taichi; Komuro, Terumasa

2009-10-01

The guinea-pig ileocaecal junction including the valve was studied by immunohistochemistry to clarify the organization of the muscle bundles, the enteric nerves and the interstitial cells of Cajal (ICC). This region clearly exhibited characteristic features in the distribution patterns of ICC in a proximal to distal direction: (1) the thickened portion of the terminal ileum immediately adjacent to the ileocecal junction contained many ICC throughout the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers, but ICC were few or absent in the rest of the ileum; (2) the ileal side of the valve contained ICC associated with the deep muscular plexus (ICC-DMP) as in the small intestine, whereas ICC-DMP were absent in the caecal side as in the caecum; (3) the valve contained many ICC-CM and ICC-LM in both the ileal and caecal sides; (4) many ICC associated with the myenteric plexus were observed in both the ileal and caecal sides of the valve, whereas they were only sparsely found in the caecum; (5) ICC were also observed around the submucosal plexus in a confined area of the terminal ileum and the ileocaecal valve. These observations provide morphological evidence that the terminal ileum and ileocaecal valve are specially equipped for their active involvement in the movement of the junctional area.

Expression and function of 5-HT4 receptors in the mouse enteric nervous system.

PubMed

Liu, Mintsai; Geddis, Matthew S; Wen, Ying; Setlik, Wanda; Gershon, Michael D

2005-12-01

The aim of the current study was to identify enteric 5-HT(4) splice variants, locate enteric 5-HT(4) receptors, determine the relationship, if any, of the 5-HT(4) receptor to 5-HT(1P) activity, and to ascertain the function of 5-HT(4) receptors in enteric neurophysiology. 5-HT(4a), 5-HT(4b), 5-HT(4e), and 5-HT(4f) isoforms were found in mouse brain and gut. The ratio of 5-HT(4) expression to that of the neural marker, synaptophysin, was higher in gut than in brain but was similar in small and large intestines. Submucosal 5-HT(4) expression was higher than myenteric. Although transcripts encoding 5-HT(4a) and 5-HT(4b) isoforms were more abundant, those encoding 5-HT(4e) and 5-HT(4f) were myenteric plexus specific. In situ hybridization revealed the presence of transcripts encoding 5-HT(4) receptors in subsets of enteric neurons, interstitial cells of Cajal, and smooth muscle cells. IgY antibodies to mouse 5-HT(4) receptors were raised, affinity purified, and characterized. Nerve fibers in the circular muscle and the neuropil in ganglia of both plexuses were highly 5-HT(4) immunoreactive, although only a small subset of neurons contained 5-HT(4) immunoreactivity. No 5-HT(4)-immunoreactive nerves were detected in the mucosa. 5-HT and 5-HT(1P) agonists evoked a G protein-mediated long-lasting inward current that was neither mimicked by 5-HT(4) agonists nor blocked by 5-HT(4) antagonists. In contrast, the 5-HT(4) agonists renzapride and tegaserod increased the amplitudes of nicotinic evoked excitatory postsynaptic currents. Enteric neuronal 5-HT(4) receptors thus are presynaptic and probably exert their prokinetic effects by strengthening excitatory neurotransmission.

Hepatocyte Growth Factor and MET Support Mouse Enteric Nervous System Development, the Peristaltic Response, and Intestinal Epithelial Proliferation in Response to Injury

PubMed Central

Avetisyan, Marina; Wang, Hongtao; Schill, Ellen Merrick; Bery, Saya; Grider, John R.; Hassell, John A.; Stappenbeck, Thaddeus

2015-01-01

Factors providing trophic support to diverse enteric neuron subtypes remain poorly understood. We tested the hypothesis that hepatocyte growth factor (HGF) and the HGF receptor MET might support some types of enteric neurons. HGF and MET are expressed in fetal and adult enteric nervous system. In vitro, HGF increased enteric neuron differentiation and neurite length, but only if vanishingly small amounts (1 pg/ml) of glial cell line-derived neurotrophic factor were included in culture media. HGF effects were blocked by phosphatidylinositol-3 kinase inhibitor and by MET-blocking antibody. Both of these inhibitors and MEK inhibition reduced neurite length. In adult mice, MET was restricted to a subset of calcitonin gene-related peptide-immunoreactive (IR) myenteric plexus neurons thought to be intrinsic primary afferent neurons (IPANs). Conditional MET kinase domain inactivation (Metfl/fl; Wnt1Cre+) caused a dramatic loss of myenteric plexus MET-IR neurites and 1–1′-dioctodecyl-3,3,3′,3′-tetramethylindocarbocyamine perchlorate (DiI) labeling suggested reduced MET-IR neurite length. In vitro, Metfl/fl; Wnt1Cre+ mouse bowel had markedly reduced peristalsis in response to mucosal deformation, but normal response to radial muscle stretch. However, whole-bowel transit, small-bowel transit, and colonic-bead expulsion were normal in Metfl/fl; Wnt1Cre+ mice. Finally, Metfl/fl; Wnt1Cre+ mice had more bowel injury and reduced epithelial cell proliferation compared with WT animals after dextran sodium sulfate treatment. These results suggest that HGF/MET signaling is important for development and function of a subset IPANs and that these cells regulate intestinal motility and epithelial cell proliferation in response to bowel injury. SIGNIFICANCE STATEMENT The enteric nervous system has many neuronal subtypes that coordinate and control intestinal activity. Trophic factors that support these neuron types and enhance neurite growth after fetal development are not well understood. We show that a subset of adult calcitonin gene-related peptide (CGRP)-expressing myenteric neurons produce MET, the receptor for hepatocyte growth factor, and that loss of MET activity affects peristalsis in response to mucosal stroking, reduces MET-immunoreactive neurites, and increases susceptibility to dextran sodium sulfate-induced bowel injury. These observations may be relevant for understanding and treating intestinal motility disorders and also suggest that enhancing the activity of MET-expressing CGRP neurons might be a useful strategy to reduce bowel inflammation. PMID:26290232

Maternal deprivation affects the neuromuscular protein profile of the rat colon in response to an acute stressor later in life.

PubMed

Lopes, Luísa V; Marvin-Guy, Laure F; Fuerholz, Andreas; Affolter, Michael; Ramadan, Ziad; Kussmann, Martin; Fay, Laurent B; Bergonzelli, Gabriela E

2008-04-30

Early life stress as neonatal maternal deprivation (MD) predisposes rats to alter gut functions in response to acute psychological stressors in adulthood, mimicking features of irritable bowel syndrome (IBS). We applied proteomics to investigate whether MD permanently changes the protein profile of the external colonic neuromuscular layer that may condition the molecular response to an acute stressor later in life. Male rat pups were separated 3 h/day from their mothers during the perinatal period and further submitted to water avoidance (WA) stress during adulthood. Proteins were extracted from the myenteric plexus-longitudinal muscle of control (C), WA and MD+WA rat colon, separated on 2D gels, and identified by mass spectrometry. MD amplified the WA-induced protein changes involved in muscle contractile function, suggesting that stress accumulation along life imbalances the muscle tone towards hypercontractility. Our results also propose a stress dependent regulation of gluconeogenesis. Secretogranin II - the secretoneurin precursor - was induced by MD. The presence of secretoneurin in myenteric ganglia may partially explain the stress-mediated modulation of gastrointestinal motility and/or mucosal inflammation previously described in MD rats. In conclusion, our findings suggest that neonatal stress alters the responses to acute stress in adulthood in intestinal smooth muscle and enteric neurons.

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quinoxalin-2-carboxamides: synthesis and pharmacological evaluation as serotonin type-3 (5-HT3) receptor antagonists.

PubMed

Mahesh, Radhakrishnan; Devadoss, Thangaraj; Pandey, Dilip Kumar; Yadav, Shushil Kumar

2011-10-01

A series of quinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT(3) receptor antagonists and synthesized by condensing the carboxylic group of quinoxalin-2-carboxylic acid with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole. The structures of the synthesized compounds were confirmed by physical and spectroscopic data. The carboxamides were evaluated for their 5-HT(3) receptor antagonisms in longitudinal muscle-myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methy-5-HT. All the synthesized compounds showed 5-HT(3) receptor antagonism, (4-benzylpiperazin-1-yl)(quinoxalin-2-yl)methanone was the most potent compound among this series.

Autonomic innervation of the fish gut.

PubMed

Olsson, Catharina

2009-01-01

The enteric nervous system follows a similar overall arrangement in all vertebrate groups. In fish, the majority of nerve cell bodies are found in the myenteric plexus, innervating muscles, blood vessels and glands. In this review, I describe similarities and differences in size, shape and transmitter content in enteric neurons in different fish species and also in comparison with other vertebrates, foremost mammals. The use of different histological and immunochemical methods is reviewed in a historical perspective including advantages and disadvantages of different methods. Lately, zebrafish have become an important model species for developmental studies of the nervous system, including the enteric nervous system, and this is briefly discussed. Finally, examples of how the enteric nervous system controls gut activity in fish is presented, focussing on the effect on gastrointestinal motility.

Cellular and molecular basis of chronic constipation: Taking the functional/idiopathic label out

PubMed Central

Bassotti, Gabrio; Villanacci, Vincenzo; Creƫoiu, Dragos; Creƫoiu, Sanda Maria; Becheanu, Gabriel

2013-01-01

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called “functional” or “idiopathic” disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of “functional” gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors’ work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality. PMID:23864772

Cellular and molecular basis of chronic constipation: taking the functional/idiopathic label out.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Creţoiu, Dragos; Creţoiu, Sanda Maria; Becheanu, Gabriel

2013-07-14

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.

Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

PubMed Central

Buckley, Maria M; O'Halloran, Ken D; Rae, Mark G; Dinan, Timothy G; O'Malley, Dervla

2014-01-01

Abstract The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin-6 (IL-6) and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg kg−1 i.p) with or without the CRFR1 antagonist antalarmin (10 mg kg−1 i.p). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (P < 0.01) and visceral pain sensitivity (P < 0.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain-associated T-type calcium channel CaV3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. PMID:25260633

[Pathological anatomy of chagasic megaesophagus].

PubMed

Adad, S J; Andrade, D C; Lopes, E R; Chapadeiro, E

1991-01-01

Systematized study was made in 56 esophagi of chronic chagasics (17 with and 39 without megas) aiming to: 1) to evaluate the esophageal caliber and thickness ranges; 2) analyse qualitative and quantitatively, the myenteric plexuses, trying to evaluate the relation of their lesions and the development of megaesophagus (ME); 3) study the lesions of the muscularis propria to verify if they contribute or not to the beginning of the process; 4) search for T. cruzi and its eventual relationship with the inflammation; 5) identify the principal mucosal alterations. It was confirmed that the severest lesions were found in the muscularis propria and in the plexures of Auerbach ganglia. In the former, the main alterations were myositis and fibrosis. The myentric plexuses showed inflammation and neuronal depopulation when compared with non-mega chagasic esophagi and even more when compared with the controls. On the other hand, there were normal caliber esophagi with severe denervation. It is possible that several factors may lead to the esophagopathy, especially to the ME. The search for T. cruzi was found positive in four out of eight esophagi with mega and in none of eight chagasic esophagi without mega. Mucosal and submucosal lesions were unremarkable and do not seem to be involved with the development of the process.

Evaluation of substance P as a neurotransmitter in equine jejunum.

PubMed

Malone, E D; Kannan, M S; Brown, D R

2000-10-01

To determine whether substance P (SP) functions as a neurotransmitter in equine jejunum. Samples of jejunum obtained from horses that did not have lesions in the gastrointestinal tract. Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscle, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 2 intensities (30 and 70 V) and various frequencies on muscle strips that were maintained at low tension or were under contraction. A neurokinin-1 receptor blocker (CP-96,345) was added to baths prior to EFS to interrupt SP neurotransmission. Additionally, direct effects of SP on muscle strips were evaluated, and SP-like immunoreactivity was localized in intestinal tissues, using indirect immunofluorescence testing. Substance P contracted circularly and longitudinally oriented muscle strips. Prior treatment with CP-96,345 altered muscle responses to SP and EFS, suggesting that SP was released from depolarized myenteric neurons. Depending on orientation of muscle strips and stimulation variables used, CP-96,345 increased or decreased the contractile response to EFS. Substance P-like immunoreactivity was detected in the myenteric plexus and circular muscle layers. Substance P appears to function as a neurotransmitter in equine jejunum. It apparently modulates smooth muscle contractility, depending on preexisting conditions. Effects of SP may be altered in some forms of intestinal dysfunction. Altering SP neurotransmission in the jejunum may provide a therapeutic option for motility disorders of horses that are unresponsive to adrenergic and cholinergic drugs.

Vagal Afferent Innervation of the Lower Esophageal Sphincter

PubMed Central

Powley, Terry L.; Baronowsky, Elizabeth A.; Gilbert, Jared M.; Hudson, Cherie N.; Martin, Felecia N.; Mason, Jacqueline K.; McAdams, Jennifer L.; Phillips, Robert J.

2013-01-01

To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions. PMID:23583280

Modulation by acetylcholine of the electrically-evoked release of [3H]-acetylcholine from the ileum of the guinea-pig.

PubMed Central

Fosbraey, P.; Johnson, E. S.

1980-01-01

1 Acetylcholine (ACh) stores within neurones of the myenteric plexus of the guinea-pig were labelled with [3H]-choline and the influence of unlabelled ACh, atropine, or atropine and unlabelled ACh on the electrically-evoked output of [3H]-ACh was evaluated. 2 Electrical transmural stimulation (5 Hz) of the ileum led to an increase in the output of [3H]-ACh over that released spontaneously. Superfusion with unlabelled ACh (6.8 microM) caused a marked reduction in the release of [3H]-ACh which was reversed by atropine (3.5 microM). Atropine itself had no effect on the electrically-evoked [3H]-ACh. 3 These experiments provide further evidence for the existence in the guinea-pig ileum of neuronal muscarinic receptors for ACh subserving an inhibitory role on transmitter release. PMID:7378653

Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto.

PubMed

Tokita, Yohei; Yamamoto, Masahiro; Satoh, Kazuko; Nishiyama, Mitsue; Iizuka, Seiichi; Imamura, Sachiko; Kase, Yoshio

2011-01-01

This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT.

[Expression of neuropeptide Y and long leptin receptor in gastrointestinal tract of giant panda].

PubMed

Luo, Qihui; Tang, Xiuying; Chen, Zhengli; Wang, Kaiyu; Wang, Chengdong; Li, Desheng; Li, Caiwu

2015-08-01

To study the expression and distribution of neuropeptide Y (NPY) and long leptin receptor (OB-Rb) in the gastrointestinal tract of giant panda, samples of three animals were collected from the key laboratory for reproduction and conservation genetics of endangered wildlife of Sichuan province, China conservation and research center for the giant panda. Paraffin sections of giant panda gastrointestinal tissue samples were observed using hematoxylin-eosin staining (HE) and strept actividin-biotin complex immunohistochemical staining (IHC). The results show that the intestinal histology of three pandas was normal and no pathological changes, and there were rich single-cell and multi-cell mucous glands, long intestinal villi and thick muscularis mucosa and muscle layer. Positive cells expressing NPY and OB-Rb were widely detected in the gastrointestinal tract by IHC methods. NPY positive nerve fibers and neuronal cell were widely distributed in submucosal plexus and myenteric plexus, especially in the former. They were arranged beaded or point-like shape. NPY positive cells were observed in the shape of ellipse and polygon and mainly located in the mucous layer and intestinal glands. OB-Rb positive cells were mainly distributed in the mucous layer and the laminae propria, especially the latter. These results confirmed that NPY and OB-Rb are widely distributed in the gut of the giant panda, which provide strong reference for the research between growth and development, digestion and absorption, and immune function.

Postoperative ileus involves interleukin-1 receptor signaling in enteric glia.

PubMed

Stoffels, Burkhard; Hupa, Kristof Johannes; Snoek, Susanne A; van Bree, Sjoerd; Stein, Kathy; Schwandt, Timo; Vilz, Tim O; Lysson, Mariola; Veer, Cornelis Van't; Kummer, Markus P; Hornung, Veit; Kalff, Joerg C; de Jonge, Wouter J; Wehner, Sven

2014-01-01

Postoperative ileus (POI) is a common consequence of abdominal surgery that increases the risk of postoperative complications and morbidity. We investigated the cellular mechanisms and immune responses involved in the pathogenesis of POI. We studied a mouse model of POI in which intestinal manipulation leads to inflammation of the muscularis externa and disrupts motility. We used C57BL/6 (control) mice as well as mice deficient in Toll-like receptors (TLRs) and cytokine signaling components (TLR-2(-/-), TLR-4(-/-), TLR-2/4(-/-), MyD88(-/-), MyD88/TLR adaptor molecule 1(-/-), interleukin-1 receptor [IL-1R1](-/-), and interleukin (IL)-18(-/-) mice). Bone marrow transplantation experiments were performed to determine which cytokine receptors and cell types are involved in the pathogenesis of POI. Development of POI did not require TLRs 2, 4, or 9 or MyD88/TLR adaptor molecule 2 but did require MyD88, indicating a role for IL-1R1. IL-1R1(-/-) mice did not develop POI; however, mice deficient in IL-18, which also signals via MyD88, developed POI. Mice given injections of an IL-1 receptor antagonist (anakinra) or antibodies to deplete IL-1α and IL-1β before intestinal manipulation were protected from POI. Induction of POI activated the inflammasome in muscularis externa tissues of C57BL6 mice, and IL-1α and IL-1β were released in ex vivo organ bath cultures. In bone marrow transplantation experiments, the development of POI required activation of IL-1 receptor in nonhematopoietic cells. IL-1R1 was expressed by enteric glial cells in the myenteric plexus layer, and cultured primary enteric glia cells expressed IL-6 and the chemokine monocyte chemotactic protein 1 in response to IL-1β stimulation. Immunohistochemical analysis of human small bowel tissue samples confirmed expression of IL-1R1 in the ganglia of the myenteric plexus. IL-1 signaling, via IL-1R1 and MyD88, is required for development of POI after intestinal manipulation in mice. Agents that interfere with the IL-1 signaling pathway are likely to be effective in the treatment of POI. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Electrical behaviour of myenteric neurones in the gastric corpus of the guinea-pig.

PubMed Central

Schemann, M; Wood, J D

1989-01-01

1. Electrical behaviour of ganglion cells in the myenteric plexus of the guinea-pig stomach was investigated using intracellular recording methods. 2. Three subpopulations were identified and classified for convenience of discussion as gastric I, II and III neurones. Gastric I neurones were characterized by repetitive spike discharge during depolarizing current pulses and by higher input resistance than the other types. Gastric II neurones discharged one or two spikes only at the onset of long-lasting depolarizing current pulses. Gastric III neurones did not discharge spikes to depolarizing current pulses and had higher membrane potentials and lower input resistances than the other types. Non-stimulus evoked discharge ('spontaneous' discharge) did not occur in any of the neurones. 3. Resting membrane potentials were generated primarily by resting K+ conductance, but were smaller than the estimated K+ equilibrium potential. Analysis based on the constant field equation predicted lower K+ conductance in gastric I than in gastric III neurones. 4. Action potentials in gastric I and II neurones were suppressed or blocked by tetrodotoxin. Spikes that were broadened by tetraethylammonium appeared to have an inward component of Ca2+ current. 5. Hyperpolarizing after-potentials were associated with the spikes of both kinds of neurones. These after-potentials had much shorter duration (less than 300 ms) than the post-spike hyperpolarization of AH/type 2 intestinal neurones and unlike intestinal neurones there was no latency between the positive after-potential of the spike and the onset of the hyperpolarization. After-hyperpolarization in the gastric neurones was enhanced when the spikes were broadened by tetraethylammonium and was suppressed by removal of Ca2+ from the bathing solution. 6. Treatment with either tetraethylammonium or 4-aminopyridine enhanced excitability and induced 'spontaneously' occurring repetitive spike discharge. 7. The electrophysiological behaviour of gastric myenteric neurones differed significantly from intestinal neurones. This was interpreted as specialization of the neural networks that control and co-ordinate the activity of vastly different effector systems in the two regions of the alimentary canal. Images Fig. 1 PMID:2621607

Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus

PubMed Central

Jin, Hong; Wang, Bin; Zhang, Li-li

2018-01-01

Background The aim of this study was to undertake a histological evaluation of the presence of eosinophils in esophageal muscle in patients with achalasia before treatment with peroral endoscopic myotomy (POEM), with clinical follow-up at one year. Material/Methods Before treatment, esophageal biopsies including mucosa and esophageal muscle were obtained from 28 patients with achalasia. Nine patients who had undergone esophagectomy for esophageal carcinoma were included in the control group. The Eckardt Score was used to evaluate the clinical symptoms of achalasia. Histology of routinely processed tissue sections was used to perform eosinophil cell counts (0 to +++), and immunohistochemistry was used to detect expression of eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and S100 protein in cases of achalasia (n=28) and controls (n=9). The findings in patients with achalasia were compared before and one year following POEM. Results Esophageal tissue from patients with achalasia showed eosinophils infiltrating into the muscularis externa in 85.7% (24/28), into the muscularis propria in 28.6% (8/28), and in 89% (25/28) there were few remaining myenteric ganglion cells, before POEM. The extent of inflammation was similar in all regions of the esophagus and between subtypes of achalasia. At one year following POEM, the Eckardt Scores between the former eosinophil (0) group and the eosinophil (+++) group were significantly different (Z=3.50, P=0.030). Conclusions Achalasia of the esophagus was associated with infiltration of the esophageal muscle by activated eosinophils and a decrease in the density of ganglion cells in the myenteric esophageal plexus. PMID:29672471

Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFNβ transgenic mice

PubMed Central

Domènech, Anna; Pasquinelli, Gianandrea; De Giorgio, Roberto; Gori, Alessandra; Bosch, Fàtima; Pumarola, Martí; Jiménez, Marcel

2011-01-01

The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFNβ transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model. PMID:22050417

TRPV2 ion channels expressed in inhibitory motor neurons of gastric myenteric plexus contribute to gastric adaptive relaxation and gastric emptying in mice.

PubMed

Mihara, Hiroshi; Suzuki, Nobuhiro; Yamawaki, Hidemoto; Tominaga, Makoto; Sugiyama, Toshiro

2013-02-01

Gastric adaptive relaxation (GAR) is impaired in ~40% of functional dyspepsia (FD) patients, and nitric oxide (NO) released from inhibitory motor neurons plays an important role in this relaxation. Although the underlying molecular mechanism of GAR is poorly understood, transient receptor potential channel vanilloid 2 (TRPV2) mechano- and chemoreceptors are expressed in mouse intestinal inhibitory motor neurons and are involved in intestinal relaxation. The aim of this study was to evaluate the distribution of TRPV2 in inhibitory motor neurons throughout the mouse gastrointestinal tract and the contribution of TRPV2 to GAR. RT-PCR and immunohistochemical analyses were used to detect TRPV2 mRNA and protein, respectively. Intragastric pressure was determined with an isolated mouse stomach. Gastric emptying (GE) in vivo was determined using a test meal. TRPV2 mRNA was detected throughout the mouse gastrointestinal tract, and TRPV2 immunoreactivity was detected in 84.3% of neuronal nitric oxide synthase-expressing myenteric neurons in the stomach. GAR, which was expressed as the rate of decline of intragastric pressure in response to volume stimuli, was significantly enhanced by the TRPV2 activator probenecid, and the enhancement was inhibited by the TRPV2 inhibitor tranilast. GE was significantly accelerated by TRPV2 agonist applications, and the probenecid-induced enhancement was significantly inhibited by tranilast coapplication. Mechanosensitive TRPV2 was expressed in inhibitory motor neurons in the mouse stomach and contributed to GAR and GE. TRPV2 may be a promising target for FD patients with impaired GAR.

Morphological evidence for novel enteric neuronal circuitry in guinea pig distal colon.

PubMed

Smolilo, D J; Costa, M; Hibberd, T J; Wattchow, D A; Spencer, Nick J

2018-07-01

The gastrointestinal (GI) tract is unique compared to all other internal organs; it is the only organ with its own nervous system and its own population of intrinsic sensory neurons, known as intrinsic primary afferent neurons (IPANs). How these IPANs form neuronal circuits with other functional classes of neurons in the enteric nervous system (ENS) is incompletely understood. We used a combination of light microscopy, immunohistochemistry and confocal microscopy to examine the topographical distribution of specific classes of neurons in the myenteric plexus of guinea-pig colon, including putative IPANs, with other classes of enteric neurons. These findings were based on immunoreactivity to the neuronal markers, calbindin, calretinin and nitric oxide synthase. We then correlated the varicose outputs formed by putative IPANs with subclasses of excitatory interneurons and motor neurons. We revealed that calbindin-immunoreactive varicosities form specialized structures resembling 'baskets' within the majority of myenteric ganglia, which were arranged in clusters around calretinin-immunoreactive neurons. These calbindin baskets directly arose from projections of putative IPANs and represent morphological evidence of preferential input from sensory neurons directly to a select group of calretinin neurons. Our findings uncovered that these neurons are likely to be ascending excitatory interneurons and excitatory motor neurons. Our study reveals for the first time in the colon, a novel enteric neural circuit, whereby calbindin-immunoreactive putative sensory neurons form specialized varicose structures that likely direct synaptic outputs to excitatory interneurons and motor neurons. This circuit likely forms the basis of polarized neuronal pathways underlying motility. © 2018 Wiley Periodicals, Inc.

Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus.

PubMed

Bulc, Michał; Gonkowski, Sławomir; Całka, Jarosław

2015-11-01

In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.

HO-1 induction in motor cortex and intestinal dysfunction in TDP-43 A315T transgenic mice.

PubMed

Guo, Yansu; Wang, Qian; Zhang, Kunxi; An, Ting; Shi, Pengxiao; Li, Zhongyao; Duan, Weisong; Li, Chunyan

2012-06-15

TAR DNA-binding protein 43 (TDP-43) has been found to be related to the pathogenesis of amyotrophic lateral sclerosis (ALS). TDP-43 A315T transgenic mice develop degeneration of specific motor neurons, and accumulation of ubiquitinated proteins has been observed in the pyramidal cells of motor cortex of these mice. In this study, we found stress-responsive HO-1 induction and no autophagic alteration in motor cortex of TDP-43 A315T transgenic mice. Glial activation, especially astrocytic proliferation, occurred in cortical layer 5 and sub-meningeal region. Interestingly, we noticed that progressively thinned colon, swollen small intestine and reduced food intake, rather than severe muscle weakness, contributed to the death of TDP-43 A315T transgenic mice. Increased TDP-43 accumulation in the myenteric nerve plexus and increased thickness of muscular layer of colon were related to the intestinal dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega

PubMed Central

Côbo, Eliângela de Castro; Silveira, Thales Parenti; Micheletti, Adilha Misson; Crema, Eduardo; Adad, Sheila Jorge

2012-01-01

To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+). PMID:22131997

Morphometric evaluation of oesophageal wall in patients with nutcracker oesophagus and ineffective oesophageal motility.

PubMed

Kim, H S; Park, H; Lim, J H; Choi, S H; Park, C; Lee, S I; Conklin, J L

2008-08-01

The pathogenesis of nutcracker oesophagus (NE) and ineffective oesophageal motility (IEM) is unclear. Damage to the enteric nervous system or smooth muscle can cause oesophageal dysmotility. We tested the hypothesis that NE and IEM are associated with abnormal muscular or neural constituents of the oesophageal wall. Oesophageal manometry was performed in patients prior to total gastrectomy for gastric cancer. The oesophageal manometries were categorized as normal (n = 7), NE (n = 13), or IEM (n = 5). Histologic examination of oesophageal tissue obtained during surgery was performed after haematoxylin and eosin (H&E) and trichrome staining. Oesophageal innervation was examined after immunostaining for protein gene product-9.5 (PGP-9.5), choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS). There were no significant differences in inner circular smooth muscle thickness or degree of fibrosis among the three groups. Severe muscle fibre loss was found in four of five patients with IEM. The density of PGP-9.5-reactive neural structures was not different among the three groups. The density of ChAT immunostaining in the myenteric plexus (MP) was significantly greater in patients with NE (P < 0.05) and the density of nNOS immunostaining in the circular muscle (CM) was significantly greater in IEM patients (P < 0.05). The ChAT/nNOS ratio in both MP and CM was significantly greater in NE patients. NE may result from an imbalance between the excitatory and inhibitory innervation of the oesophagus, because more than normal numbers of ChAT-positive myenteric neurones are seen in NE. Myopathy and/or increased number of nNOS neurones may contribute to the hypocontractile motor activity of IEM.

Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors.

PubMed

Yang, Xiao; Xi, Tao-Fang; Li, Yu-Xian; Wang, Hai-Hong; Qin, Ying; Zhang, Jie-Ping; Cai, Wen-Ting; Huang, Meng-Ting; Shen, Ji-Qiao; Fan, Xi-Min; Shi, Xuan-Zheng; Xie, Dong-Ping

2014-08-21

To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. Colon transit was slower in the cold group than in the control group (P < 0.05). Colonic smooth muscle contractile response to oxytocin decreased, and the inhibitory effect of oxytocin on muscle contractility was enhanced by cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P < 0.05). Atosiban and tetrodotoxin inhibited the effect of oxytocin on colonic motility. Oxytocin receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P < 0.05). Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P < 0.05). However, in ovariectomized rats, estradiol treatment increased blood oxytocin, and the response of colonic muscle strips to oxytocin was attenuated. Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

Full-field optical coherence microscopy is a novel technique for imaging enteric ganglia in the gastrointestinal tract

PubMed Central

CORON, E.; AUKSORIUS, E.; PIERETTI, A.; MAHÉ, M. M.; LIU, L.; STEIGER, C.; BROMBERG, Y.; BOUMA, B.; TEARNEY, G.; NEUNLIST, M.; GOLDSTEIN, A. M.

2013-01-01

Background Noninvasive methods are needed to improve the diagnosis of enteric neuropathies. Full-field optical coherence microscopy (FFOCM) is a novel optical microscopy modality that can acquire 1 μm resolution images of tissue. The objective of this research was to demonstrate FFOCM imaging for the characterization of the enteric nervous system (ENS). Methods Normal mice and EdnrB−/− mice, a model of Hirschsprung’s disease (HD), were imaged in three-dimensions ex vivo using FFOCM through the entire thickness and length of the gut. Quantitative analysis of myenteric ganglia was performed on FFOCM images obtained from whole-mount tissues and compared with immunohistochemistry imaged by confocal microscopy. Key Results Full-field optical coherence microscopy enabled visualization of the full thickness gut wall from serosa to mucosa. Images of the myenteric plexus were successfully acquired from the stomach, duodenum, colon, and rectum. Quantification of ganglionic neuronal counts on FFOCM images revealed strong interobserver agreement and identical values to those obtained by immunofluorescence microscopy. In EdnrB−/− mice, FFOCM analysis revealed a significant decrease in ganglia density along the colorectum and a significantly lower density of ganglia in all colorectal segments compared with normal mice. Conclusions & Inferences Full-field optical coherence microscopy enables optical microscopic imaging of the ENS within the bowel wall along the entire intestine. FFOCM is able to differentiate ganglionic from aganglionic colon in a mouse model of HD, and can provide quantitative assessment of ganglionic density. With further refinements that enable bowel wall imaging in vivo, this technology has the potential to revolutionize the characterization of the ENS and the diagnosis of enteric neuropathies. PMID:23106847

The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry

PubMed Central

Kahrilas, Peter J.; Boeckxstaens, Guy

2013-01-01

High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of achalasia. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific. Laboratory studies indicate that achalasia is an autoimmune disease in which esophageal myenteric neurons are attacked in a cell-mediated and antibody-mediated immune response against an uncertain antigen. This autoimmune response could be related to infection of genetically predisposed subjects with herpes simplex virus 1, although there is substantial heterogeneity among patients. At one end of the spectrum is complete aganglionosis in patients with end-stage or fulminant disease. At the opposite extreme is type III (spastic) achalasia, which has no demonstrated neuronal loss but only impaired inhibitory postganglionic neuron function; it is often associated with accentuated contractility and could be mediated by cytokine-induced alterations in gene expression. Distinct from these extremes is progressive plexopathy, which likely arises from achalasia with preserved peristalsis and then develops into type II achalasia and then type I achalasia. Variations in its extent and rate of progression are likely related to the intensity of the cytotoxic T-cell assault on the myenteric plexus. Moving forward, we need to integrate the knowledge we have gained into treatment paradigms that are specific for individual phenotypes of achalasia and away from the one-size-fits-all approach. PMID:23973923

Substance P provoked gamma-aminobutyric acid release from the myenteric plexus of the guinea-pig small intestine.

PubMed Central

Tanaka, C; Taniyama, K

1985-01-01

The release of [3H]gamma-aminobutyric acid (GABA) from the isolated small intestine of the guinea-pig pre-loaded with [3H]GABA was measured in the presence of substance P and vasoactive intestinal polypeptide (VIP). Substance P (10(-10)-10(-7) M) produced a dose-dependent increase in the fractional rate of [3H]GABA release. VIP, even at 10(-7) M, did not affect the spontaneous [3H]GABA release nor the release of [3H]GABA evoked by electrical transmural stimulation (0.5 ms, 15 V, 10 Hz for 30 s). The release of endogenous GABA from the isolated small intestine was measured in the presence of substance P (10(-9) M). After 60 min superfusion, the spontaneous release of GABA was 4.61 +/- 0.14 pmol min-1 g-1 wet wt. (n = 20). Substance P (10(-9) M) produced an approximate 2-fold spontaneous release of endogeneous GABA (8.74 +/- 0.21 pmol min-1 g-1 wet wt. (n = 10)). Perfusion with Ca-free medium containing 1 mM-EGTA and tetrodotoxin (3 X 10(-7) M) inhibited the release of endogenous GABA evoked by substance P (10(-9) M). (D-Pro2, D-Trp7,9) substance P (10(-6) M) antagonized the release of endogenous GABA evoked by substance P (10(-9) M). These results indicate that substance P induces a neuronal release of GABA through its receptor located in the guinea-pig small intestine. Substance P (10(-11)-10(-7) M) produced a dose-dependent increase in the fractional rate of [3H]acetylcholine (ACh) release from the isolated small intestine pre-loaded with [3H]choline. The release of [3H]ACh evoked by substance P (10(-9) M) was inhibited by perfusion with Ca-free medium containing 1 mM-EGTA, tetrodotoxin (3 X 10(-7) M) and (D-Pro2, D-Trp7,9)substance P (10(-6) M). Bicuculline (10(-6) M) inhibited the release of [3H]ACh evoked by substance P (10(-9) M) by 68.1 +/- 4.6% (n = 5), thereby suggesting that the substance P-evoked ACh release is partly mediated through the endogenous GABA released by substance P. These results provide evidence for the neurotransmitter role of GABA and a possible excitatory role of substance P on the GABAergic neurones in the myenteric plexus of the guinea-pig small intestine. PMID:2410602

[Jejunal myenteric denervation induced by benzalkonium chloride].

PubMed

Ramalho, F S; Santos, G C; Ramalho, L N; Kajiwara, J K; Zucoloto, S

1994-01-01

The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

Distribution of enkephalin immunoreactivity in sympathetic prevertebral ganglia and digestive tract of guinea-pigs and rats.

PubMed

Herbrecht, F; Bagnol, D; Cucumel, K; Jule, Y; Cupo, A

1995-05-04

The aim of the present study was to determine the distribution of methionine-enkephalin (ME) and leucine-enkephalin (LE) immunoreactivity in the sympathetic prevertebral ganglia (coeliac plexus and inferior mesenteric ganglion) and in the myenteric plexus-muscular layer complex of the digestive tract in guinea-pigs and rats. This study was performed using the same immunological approaches including radioimmunoassays and HPLC characterization as those used previously on cats in order to be able to make inter-region and inter-species comparisons. In rat and guinea-pig prevertebral ganglia, the distributions of the enkephalin immunoreactivities were comparable and were characterized by a low ME/LE concentration ratio, of less than 1. In the digestive tract of rats, the enkephalin immunoreactivities were homogeneously distributed, whereas in guinea-pigs, they were found to be very low in the lower oesophageal sphincter and high in the duodenum. In both species, the ME/LE concentration ratio was around 2. The ME/LE concentration ratio determined in the present study in peripheral nervous structures was much lower than that determined previously in the rat brain. Radioimmunoassay and biochemical data might indicate that different mechanisms are responsible for the processing and/or degradation of enkephalins in the central and peripheral nervous systems. The present study provides further evidences that there are tissue- and species-dependent differences in the distribution of enkephalin immunoreactivities. These differences should be taken into consideration when dealing with the effects and the role of enkephalins in the nervous control of intestinal motility in mammals.

Histopathologic observations of anorectal abnormalities in anal atresia.

PubMed

Meier-Ruge, W A; Holschneider, A M

2000-01-01

Over the years from 1992 to 1997, 41 anorectal malformations (ARM) with histopathologic alterations were investigated to determine which morphologic abnormalities of the distal rectum accompany ARMs. Three other cases showed normal neuromuscular morphology; 9 further cases could not be evaluated owing to scanty biopsies. All resected specimens were caudocranially coiled and cryostat cut at -20 degrees C into serial sections, which were stained with a lactic dehydrogenase, succinic dehydrogenase, nitroxide synthase, and acetylcholinesterase reaction as well as hemalum and sirius red. Ten low, 15 intermediate, and 10 high forms of anal atresia (AA) were studied. In addition, six cloacal abnormalities were investigated. In 7 cases (17%) (5 intermediate, 2 low AAs), the characteristics of Hirschsprung's disease were observed. Oligoneuronal hypoganglionosis of the myenteric plexus proximal to the anal floor was diagnosed in 7 AAs (12%). In 10 children with high-type AA and resection of 1-5 cm distal rectum and in all cloacal anomalies (n = 6) defects of the muscularis propria were seen in the rectal-atresia sac. These defects were characterized by hypoplasia of the circular-muscle layer and/or the internal anal sphincter (IAS). Intestinal neuronal dysplasia of the submucous plexus was most frequently observed (12%) in high-type AA. A correlation between innervation anomalies or anomalies of the muscularis propria and the type of fistula could not be seen. In conclusion, all cases with high-type AA and cloacal anomalies were characterized by anomalies of the muscularis propria and/or IAS but this was not the case in intermediate and low-type AAs. Anomalies of the enteric nervous system were diagnosed in 60% of AAs.

Recordings from human myenteric neurons using voltage-sensitive dyes.

PubMed

Vignali, Sheila; Peter, Nadine; Ceyhan, Güralp; Demir, Ihsan Ekin; Zeller, Florian; Senseman, David; Michel, Klaus; Schemann, Michael

2010-10-15

Voltage-sensitive dye (VSD) imaging became a powerful tool to detect neural activity in the enteric nervous system, including its routine use in submucous neurons in freshly dissected human tissue. However, VSD imaging of human myenteric neurons remained a challenge because of limited visibility of the ganglia and dye accessibility. We describe a protocol to apply VSD for recordings of human myenteric neurons in freshly dissected tissue and myenteric neurons in primary cultures. VSD imaging of guinea-pig myenteric neurons was used for reference. Electrical stimulation of interganglionic fiber tracts and exogenous application of nicotine or elevated KCl solution was used to evoke action potentials. Bath application of the VSDs Annine-6Plus, Di-4-ANEPPS, Di-8-ANEPPQ, Di-4-ANEPPDHQ or Di-8-ANEPPS revealed no neural signals in human tissue although most of these VSD worked in guinea-pig tissue. Unlike methylene blue and FM1-43, 4-Di-2-ASP did not influence spike discharge and was used in human tissue to visualize myenteric ganglia as a prerequisite for targeted intraganglionic VSD application. Of all VSDs, only intraganglionic injection of Di-8-ANEPPS by a volume controlled injector revealed neuronal signals in human tissue. Signal-to-noise ratio increased by addition of dipicrylamine to Di-8-ANEPPS (0.98±0.16 vs. 2.4±0.62). Establishing VSD imaging in primary cultures of human myenteric neurons led to a further improvement of signal-to-noise ratio. This allowed us to routinely record spike discharge after nicotine application. The described protocol enabled reliable VSD recordings from human myenteric neurons but may also be relevant for the use of other fluorescent dyes in human tissues. Copyright © 2010 Elsevier B.V. All rights reserved.

Structural determination and histochemical localization of ghrelin in the red-eared slider turtle, Trachemys scripta elegans.

PubMed

Kaiya, Hiroyuki; Sakata, Ichiro; Kojima, Masayasu; Hosoda, Hiroshi; Sakai, Takafumi; Kangawa, Kenji

2004-08-01

We purified ghrelin peptide and determined the cDNA sequence encoding the precursor protein from the stomach of the red-eared slider turtle, Trachemys scripta elegans. The Trachemys ghrelin is comprised of 25-amino acids and has the sequence GSSFLSPEYQNTQQRKDPKKHTKLN. The third serine residue was modified by n-octanoic (C8:0), decanoic (C10:0) or unsaturated decanoic acid (C10:1). The carboxyl-terminal end of the peptide was not amidated, as seen in the ghrelins of other land vertebrates. Quantitative real-time PCR analysis revealed high levels of gene expression in the stomach and moderate levels in the large intestine and pancreas. Histochemical studies of turtle stomach revealed that ghrelin-immunopositive (ghrelin-ip) cells, which were small and round, were observed in the mucosal layer of the stomach but not in the myenteric plexus, and ghrelin-mRNA-expressing (ghrelin-ex) cells detected by in situ hybridization were scattered in a similar distribution as ghrelin-ip cells. These results indicate that ghrelin is present in reptiles.

Nitric Oxide Synthase and Neuronal NADPH Diaphorase are Identical in Brain and Peripheral Tissues

NASA Astrophysics Data System (ADS)

Dawson, Ted M.; Bredt, David S.; Fotuhi, Majid; Hwang, Paul M.; Snyder, Solomon H.

1991-09-01

NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in medium to large aspiny neurons. These same neurons colocalize with somatostatin and neuropeptide Y immunoreactivity. NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in the pedunculopontine nucleus with choline acetyltransferase-containing cells and are also colocalized in amacrine cells of the inner nuclear layer and ganglion cells of the retina, myenteric plexus neurons of the intestine, and ganglion cells of the adrenal medulla. Transfection of human kidney cells with NO synthase cDNA elicits NADPH diaphorase staining. The ratio of NO synthase to NADPH diaphorase staining in the transfected cells is the same as in neurons, indicating that NO synthase fully accounts for observed NADPH staining. The identity of neuronal NO synthase and NADPH diaphorase suggests a role for NO in modulating neurotoxicity.

Discovery of new anti-depressants from structurally novel 5-HT3 receptor antagonists: design, synthesis and pharmacological evaluation of 3-ethoxyquinoxalin-2-carboxamides.

PubMed

Mahesh, Radhakrishnan; Devadoss, Thangaraj; Pandey, Dilip Kumar; Bhatt, Shvetank

2011-02-15

A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT(3) receptor antagonist using ligand-based approach. The desired carboxamides were synthesized from the key intermediate, 3-ethoxyquinoxalin-2-carboxylic acid by coupling with appropriate amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT(3) receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methy-5-HT, which was expressed in the form of pA(2) values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1-yl)methanone was found to be the most active compound, which expressed a pA(2) value of 7.7. In forced swim test, the compounds with higher pA(2) value exhibited good anti-depressant-like activity and compounds with lower pA(2) value failed to show activity as compared to the vehicle-treated group. Copyright © 2010 Elsevier Ltd. All rights reserved.

Diagnosis of Hirschsprung's disease with particular emphasis on histopathology. A systematic review of current literature

PubMed Central

Szylberg, Łukasz

2014-01-01

Hirschsprung's disease (HD) is a disorder that involves several medical specialties such as paediatric gastroenterology, paediatric surgery, and pathology. Hirschsprung's disease is a congenital bowel innervation disorder characterised by the absence of ganglion cells in myenteric (Auerbach) and submucosal (Meissner) plexus in the distal colon in its classical form. Rapid and accurate diagnosis of HD is a key element in further treatment patterns. The efficiency of different diagnostic methods used in HD patients may vary. Using one limited diagnostic procedure can lead to as much as a few per cent of overlooked cases. In recent years, rectal biopsy was recognised as an important diagnostic tool that allows for a definitive HD diagnosis with an accuracy of 95% of cases. A correct diagnosis depends on the localisation of the biopsied sample, its representativeness, the number of specimens, and proper interpretation of microscopic studies supported by histochemical and immunohistochemical methods. When several methods are used and all diagnostic criteria are used, the diagnostic sensitivity can almost eliminate cases of undiagnosed patients. PMID:25395999

Detection and comparison of nitric oxide in clinically healthy horses and those with naturally acquired strangulating large colon volvulus

PubMed Central

2005-01-01

Abstract The objective of the study was to determine whether nitric oxide (NO) is present in clinically healthy horses (control) under basal conditions, and if it increases secondary to naturally acquired strangulating large colon volvulus (affected). Eleven affected horses and 10 controls were studied. Jugular venous blood, abdominal fluid, and urine were collected. The NO concentrations were standardized to the creatinine concentration in the respective samples. A biopsy specimen collected from the large colon pelvic flexure at surgery was divided into subsections for processing for inducible nitric synthase (iNOS) and nitrotyrosine (NT) immunohistochemical staining and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical staining. There were no significant differences in plasma, abdominal fluid, or urine NO concentrations between affected and control horses. There was a significant decrease in submucosal arteriolar and venular endothelium, submucosal plexus, mucosal leukocyte, mucosal and musclaris vasculature, and myenteric plexus NADPH diaphorase staining in affected versus control horses. There was a significant increase in iNOS staining in mucosal leukocytes and vasculature in affected versus control horses. Other than a greater number of positively stained mucosal leukocytes in affected horses, there were no significant differences between affected and control horses for NT staining. The presence of NADPH diaphorase staining in the endothelium and submucosal neurons suggests endothelial and neuronal NOS are present under basal conditions in the large colon of horses. Increased iNOS and NT staining in mucosal leukocytes of affected horses suggests involvement of the NO pathway in large colon volvulus. The reasons for the lack of a significant difference in plasma, abdominal fluid, and urine NO concentrations between affected and control horses are unknown. PMID:15971674

Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation.

PubMed

Heckert, J; Thomas, R M; Parkman, H P

2017-08-01

The aims of this study were to describe the histology in gastroparesis, specifically to relate histopathology to etiology of gastroparesis (idiopathic and diabetic gastroparesis), gastric emptying, and clinical response to gastric electric stimulation. Full thickness gastric body sections obtained during insertion of gastric stimulator in gastroparetics were stained with Hematoxylin & Eosin, Masson Trichrome and immunohistochemical stains for Neuron-Specific Enolase and c-Kit. In all, 145 gastroparetics (71 diabetics, 71 idiopathic, 2 post-surgical, and 1 chronic intestinal pseudo-obstruction) had full thickness gastric body biopsies. A lymphocytic infiltrate was seen in the intermyenteric plexus in 22 diabetic and 23 idiopathic gastroparesis patients. Fibrosis was present in the inner circular layer in 13 diabetic and 15 idiopathics and in the outer longitudinal layer in 46 diabetic and 51 idiopathics. Diabetic gastroparesis had less ganglion cells (3.27±1.82 vs 4.81±2.81/hpf; P<.01) and less ganglia (0.90±0.44 vs 1.10±0.50/hpf; P=.01) than idiopathic gastroparesis. Interstitial cells of Cajal (ICC) count was slightly lower in the inner circular layer in diabetic than idiopathics (2.77±1.47 vs 3.18±1.34/hpf; P=.08). Delayed gastric emptying was associated with reduced ICCs in the myenteric plexus. Global therapeutic response to gastric electric stimulation was inversely related to ganglia/hpf (R=-.22; P=.008). In diabetics, improvements in nausea, vomiting, and abdominal pain were inversely related to fibrosis. Histologic assessment of full thickness gastric biopsy specimens allows correlation of histopathology to the gastroparesis disease process, its etiology, gastric emptying, and response to gastric electric stimulation treatment. © 2017 John Wiley & Sons Ltd.

Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

PubMed

van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

2016-05-01

Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom.

Strain-specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice

PubMed Central

Neal, Kathleen B; Parry, Laura J; Bornstein, Joel C

2009-01-01

Serotonin (5-HT) powerfully affects small intestinal motility and 5-HT-immunoreactive (IR) neurones are highly conserved between species. 5-HT synthesis in central neurones and gastrointestinal mucosa depends on tissue-specific isoforms of the enzyme tryptophan hydroxylase (TPH). RT-PCR identified strain-specific expression of a polymorphism (1473C/G) of the tph2 gene in longitudinal muscle–myenteric plexus preparations of C57Bl/6 and Balb/c mice. The former expressed the high-activity C allele, the latter the low-activity G allele. Confocal microscopy was used to examine close contacts between 5-HT-IR varicosities and myenteric neurones immunoreactive for neuronal nitric oxide synthase (NOS) or calretinin in these two strains. Significantly more close contacts were identified to NOS- (P < 0.05) and calretinin-IR (P < 0.01) neurones in C57Bl/6 jejunum (NOS 1.6 ± 0.3, n= 52; calretinin 5.2 ± 0.4, n= 54), than Balb/c jejunum (NOS 0.9 ± 0.2, n= 78; calretinin 3.5 ± 0.3, n= 98). Propagating contractile complexes (PCCs) were identified in the isolated jejunum by constructing spatiotemporal maps from video recordings of cannulated segments in vitro. These clusters of contractions usually arose towards the anal end and propagated orally. Regular PCCs were initiated at intraluminal pressures of 6 cmH2O, and abolished by tetrodotoxin (1 μm). Jejunal PCCs from C57Bl/6 mice were suppressed by a combination of granisetron (1 μm, 5-HT3 antagonist) and SB207266 (10 nm, 5-HT4 antagonist), but PCCs from Balb/c mice were unaffected. There were, however, no strain-specific differences in sensitivity of longitudinal muscle contractions to exogenous 5-HT or blockade of 5-HT3 and 5-HT4 receptors. These data associate a genetic difference with significant structural and functional consequences for enteric neural serotonergic pathways in the jejunum. PMID:19064621

Substance P and the neurokinin-1 receptor expression in dog ileum with and without inflammation.

PubMed

Polidoro, Giulia; Giancola, Fiorella; Fracassi, Federico; Pietra, Marco; Bettini, Giuliano; Asti, Martina; Chiocchetti, Roberto

2017-10-01

In the gastrointestinal tract, the tachykinin Substance P (SP) is involved in motility, fluid and electrolyte secretion, and blood flow and regulation of immunoinflammatory response. SP exerts its biological activity on target cells by interacting mainly with the neurokinin-1 receptor (NK 1 R). The present study aims to quantify the percentage of SP-immunoreactive (SP-IR) enteric neurons and the density of SP-IR nerve fibers in the ileum of control dogs (CTRL-dogs; n=7) vs dogs with spontaneous ileal inflammation (INF-dogs; n=8). In addition, the percentage of enteric neurons bearing NK 1 R, and nitrergic neurons (nNOS-IR) expressing NK 1 R immunoreactivity were evaluated in both groups. The percentages of SP-IR neurons were similar in CTRL- and INF-dogs, in either the myenteric (MP) (15±8% vs. 16±7%, respectively) and submucosal plexus (SMP) (26±7% vs. 24±14%, respectively). In INF-dogs, the density of SP-IR mucosal nerve fibers showed a trend to decrease (P=0.07). Myenteric neurons of CTRL- and INF-dogs expressed similar percentages of NK 1 R-immunoreactivity (39±5% vs. 38±20%, respectively). Submucosal NK 1 R-IR neurons were occasionally observed in a CTRL-dog. MP nitrergic neurons bearing NK 1 R showed a trend to decrease in INF-dogs vs. CTRL- dogs (41±22% vs. 65±10%, respectively; P=0.11). In INF-dogs, muscle cells and immune cells overexpressed NK 1 R immunoreactivity. These findings should be taken as a warning for possible intestinal motility disorders, which might occur during administration of NK 1 R-antagonist drugs. Conversely, the strong expression of NK 1 R immunoreactivity observed in muscle and mucosal immune cells of inflamed tissues may provide a rationale for the use of NK 1 R antagonist drugs in the treatment of intestinal inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

No reduction with ageing of the number of myenteric neurons in benzalkonium chloride treated rats.

PubMed

Garcia, S B; Demarzo, M M P; Vinhadeli, W S; Llorach-Velludo, M A; Zoteli, J; Herrero, C F P S; Zucoloto, S

2002-10-04

The number of myenteric neurons may be reduced by topical serosal application of benzalkonium chloride (BAC). We studied the effects of ageing in the population of neurons that survive after the application of BAC. Ten treated and ten control animals were killed at intervals of 2, 6, 12 and 18 months after the surgery. We performed myenteric neurons counting in serially cut histological preparations of the descending colon. The control animals revealed a continuous loss of myenteric neurons number with increasing of age. Interestingly, contrary to control animals, the BAC-treated rats presented no neuron loss with ageing at any experimental time. The reasons for their survival with ageing could be related to a neuroplasticity phenomenon.

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

PubMed

Castell, J A; Johnston, B T; Colcher, A; Li, Q; Gideon, R M; Castell, D O

2001-08-01

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

An immunohistochemical study of the gut neuroendocrine system in juvenile pejerrey Odontesthes bonariensis (Valenciennes).

PubMed

Vigliano, F A; Muñoz, L; Hernández, D; Cerutti, P; Bermúdez, R; Quiroga, M I

2011-03-01

In this study, several neuropeptides were identified by immunohistochemistry in neuroendocrine cells (NEC) located in the gut epithelium and nerve cell bodies of the enteric nervous system of pejerrey Odontesthes bonariensis, a species that is a promising candidate for intensive aquaculture. The neuropeptides involved in orexigenic or anorexigenic action, i.e. gastrin, cholecystokinin-8, neuropeptide Y and calcitonin gene-related peptide (CGRP), displayed a significantly higher number of immunoreactive NECs in the anterior intestine, suggesting that this region of the gut plays an important role in the peripheral control of food intake. On the other hand, leu-enkephalin and vasoactive intestinal peptide (VIP), both associated with the modulation of the enteric immune system, showed no significant variations in the mean value of immunopositive NECs between the anterior and posterior intestine. This may indicate that their activity is required at a similar level along the entire gut. In addition, CGRP and VIP-immunoreactive neurons and nerve fibres were observed in the myenteric plexus, which might exert synergistic effects with the neuropeptides immunolocalized in NECs. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Response of the gut neuroendocrine system of Leuciscus cephalus (L.) to the presence of Pomphorhynchus laevis Müller, 1776 (Acanthocephala).

PubMed

Bosi, G; Domeneghini, C; Arrighi, S; Giari, L; Simoni, E; Dezfuli, B S

2005-04-01

Immunohistochemical tests were applied to sections of intestine of uninfected and Pomphorhynchus laevis Muller-infected chub, Leuciscus cephalus (L.) using 15 different antisera. Nerve cell bodies and fibres immunoreactive (IR) to the anti-bombesin, -Cholecystokinin-8 (CCK-8), -galanin, -Gastrin-Releasing Peptide (-GRP), -Nitric Oxide Synthase (-NOS), -Substance P (-SP), and -Vasoactive Intestinal Peptide (-VIP) sera were observed in the myenteric plexus of uninfected chub. The density of nerve components immunoreactive to these antisera was high in the intestine of the infected fish, especially near the site of attachment. Moreover, numerous nerve fibres, immunoreactive to anti-bombesin, -GRP, -galanin, -SP, and -VIP sera, were encountered in the connective tissue capsule surrounding the bulb and proboscis of P. laevis. The occurrence of P. laevis in the chub gut significantly increased the number of endocrine cells per intestinal fold immunoreactive to galanin, met-enkephalin and leu-enkephalin antisera. CCK-8, Neuropeptide Y and glucagon-like immunoreactive cells were less numerous in the intestine of infected chub. A large number of cells in the tunica propria-submucosa of L. cephalus infected with P. laevis were immunoreactive to anti-serotonin and -leu-enkephalin sera.

Effect of CB1 Ligands on Neurogenic and Myogenic Contractile Responses in the Guinea-Pig Ileum.

PubMed

Donnerer, Josef; Liebmann, Ingrid

2018-01-01

This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects. The allyl isothiocyanate (mustard oil, 100 µmol/L) induced a relaxant effect in the guinea-pig ileum, which can be regarded as neurogenic and myogenic, was augmented by (+)-WIN 55212-2, and inhibited by SR-141716A. (+)-WIN 55212-2 only moderately modified the 60 mmol/L KCl-evoked contractions. These results provide functional evidence that the CB1 agonist (+)-WIN 55212-2-induced inhibitory effects in the guinea-pig ileum are exerted both at the neuronal as well as at the intestinal smooth muscle cell level. © 2018 S. Karger AG, Basel.

Effects of Allyl Isothiocyanate, Acetaminophen, and Dipyrone in the Guinea-Pig Ileum.

PubMed

Donnerer, Josef; Liebmann, Ingrid

2017-01-01

Allyl isothiocyanate (AITC, mustard oil, 50-200 µmol/l), depending on specific dosages, inhibited the cholinergic twitch response in the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. AITC also induced short-lasting contractile responses, and decreases of the basal tone of the LMMP strip at low concentrations and increases at high concentrations. Hexamethonium, a blocker of nicotinic ganglionic transmission, was able to prevent the AITC-evoked inhibitory effect, an effect that was also observed with the opioid antagonist naloxone. The P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid and guanethidine had no significant influence on the inhibitory effect of AITC. Since AITC also reduced the electrical stimulation-induced myogenic smooth muscle contractions in the LMMP preparation, its contractile and relaxant actions can be regarded as neurogenic and myogenic in nature. The analgesics, acetaminophen (paracetamol, 100-500 µmol/l) and dipyrone (metamizole, 100-500 µmol/l), reduced both the cholinergic twitch and the myogenic contractions in the LMMP strip to the same extent; therefore, their action in the intestinal smooth muscle can be regarded as myogenic spasmolytic in nature. © 2016 S. Karger AG, Basel.

Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid- and lipopolysaccharide-induced TLR4 signalling.

PubMed

Reichardt, François; Chassaing, Benoit; Nezami, Behtash Ghazi; Li, Ge; Tabatabavakili, Sahar; Mwangi, Simon; Uppal, Karan; Liang, Bill; Vijay-Kumar, Matam; Jones, Dean; Gewirtz, Andrew T; Srinivasan, Shanthi

2017-03-01

A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility. The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight without blood glucose alteration. Dysbiosis was exhibited after 6 weeks of feeding, as reflected by increased fecal LPS and bacterial metabolites and concomitant higher plasma FFA. The numbers of nitrergic myenteric neurons were reduced in the proximal colon after 9 and 12 weeks of WD and this was also associated with delayed colonic transit. WD-fed Toll-like receptor 4 (TLR4) -/- mice did not exhibit myenteric cell loss or dysmotility. Finally, LPS (0.5-2 ng·ml -1 ) and palmitate (20 and 30 μm) acted synergistically to induce neuronal cell death in vitro, which was prevented by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. In conclusion, WD-feeding results in increased levels of FFA and microbiota that, even in absence of hyperglycaemia or overt endotoxaemia, synergistically induce TLR4-mediated neurodegeneration and dysmotility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Two affinities for a single antagonist at the neuronal NK1 tachykinin receptor: evidence from quantitation of receptor endocytosis

PubMed Central

Jenkinson, Karl M; Southwell, Bridget R; Furness, John B

1999-01-01

In smooth muscle contractility assays, many NK1 receptor (NK1r) antagonists inhibit responses to the neurotransmitter, substance P (SP), and its analogue, septide, with markedly different potency, leading to the proposal that there is a septide-preferring receptor related to the NK1r.We used fluorescence immunohistochemistry and confocal microscopy to visualize agonist-induced NK1r endocytosis and analyse agonist/antagonist interactions at native NK1r in neurons of the myenteric plexus of guinea-pig ileum.SP and septide gave sigmoid log concentration-response curves and were equipotent in inducing NK1r endocytosis.The NK1r antagonists, CP-99994 (2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine dihydrochloride and MEN-10581, cyclo(Leuψ[CH2NH]Lys(benzyloxycarbonyl)-Gln-Trp-Phe-βAla) were both more potent in inhibiting endocytosis (50× and 8× greater respectively) against septide than against SP.The results suggest that SP and septide interact differently with the NK1r, and that a single antagonist can exhibit different affinities at a single NK1r population, depending on the agonist with which it competes. Thus it may not be necessary to posit a separate septide-preferring tachykinin receptor. PMID:10051129

Two affinities for a single antagonist at the neuronal NK1 tachykinin receptor: evidence from quantitation of receptor endocytosis.

PubMed

Jenkinson, K M; Southwell, B R; Furness, J B

1999-01-01

1. In smooth muscle contractility assays, many NK1 receptor (NK1r) antagonists inhibit responses to the neurotransmitter, substance P (SP), and its analogue, septide, with markedly different potency, leading to the proposal that there is a septide-preferring receptor related to the NK1r. 2. We used fluorescence immunohistochemistry and confocal microscopy to visualize agonist-induced NK1r endocytosis and analyse agonist/antagonist interactions at native NK1r in neurons of the myenteric plexus of guinea-pig ileum. 3. SP and septide gave sigmoid log concentration-response curves and were equipotent in inducing NK1r endocytosis. 4. The NK1r antagonists, CP-99994 (2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine dihydrochloride and MEN-10581, cyclo(Leu,[CH2NH]Lys(benzyloxycarbonyl)-Gln-Trp-Phe-betaAla) were both more potent in inhibiting endocytosis (50 x and 8 x greater respectively) against septide than against SP. 5. The results suggest that SP and septide interact differently with the NK1r, and that a single antagonist can exhibit different affinities at a single NK1r population, depending on the agonist with which it competes. Thus it may not be necessary to posit a separate septide-preferring tachykinin receptor.

Morphological and functional changes after benzalkonium chloride treatment of the small intestinal Thiry-Vella loop in rats.

PubMed

Móricz, K; Gyetvai, B; Bárdos, G

1998-08-01

The aim of this work was to study the effects of benzalkonium chloride (BAC) treatment on the small intestine and its functioning in rats surgically prepared with Thiry-Vella intestinal loop. The loops were treated with either BAC, which ablated much of the myenteric plexus and extrinsic innervation, or with physiological saline (SAL). In vivo drinking experiments were performed to examine the effect on fluid intake and behavioral indices of distending the loop with a balloon. Spontaneous motility and its changes induced by acetylcholine (ACh) and histamine (His) were studied on isolated stripes in vitro. Finally, samples from the loops were examined histologically. Though reduction of the cell number was less than expected and no differences of the thickness of the muscular layer between the two groups was observed, BAC treatment altered the pattern of spontaneous activity and also the sensitivity to ACh and His in isolated stripes. In vivo distension of the SAL-treated loops reduced fluid intake and produced signs of aversivity; these effects were absent in the BAC-treated group. Our results show that despite the differences in the degree of ablation from those obtained by others, BAC treatment can be used to study the mechanisms underlying the effects of the enteral stimuli on the behavior.

Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease

PubMed Central

Villanacci, Vincenzo; Sidoni, Angelo; Nascimbeni, Riccardo; Dore, Maria P; Binda, Gian A; Bandelloni, Roberto; Salemme, Marianna; Del Sordo, Rachele; Cadei, Moris; Manca, Alessandra; Bernardini, Nunzia; Maurer, Christoph A; Cathomas, Gieri

2015-01-01

Background Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. Objectives Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. Methods We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. Results Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. Conclusions In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease. PMID:26668745

Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Sidoni, Angelo; Nascimbeni, Riccardo; Dore, Maria P; Binda, Gian A; Bandelloni, Roberto; Salemme, Marianna; Del Sordo, Rachele; Cadei, Moris; Manca, Alessandra; Bernardini, Nunzia; Maurer, Christoph A; Cathomas, Gieri

2015-12-01

Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease.

Birthdating of myenteric neuron subtypes in the small intestine of the mouse.

PubMed

Bergner, Annette J; Stamp, Lincon A; Gonsalvez, David G; Allison, Margaret B; Olson, David P; Myers, Martin G; Anderson, Colin R; Young, Heather M

2014-02-15

There are many different types of enteric neurons. Previous studies have identified the time at which some enteric neuron subtypes are born (exit the cell cycle) in the mouse, but the birthdates of some major enteric neuron subtypes are still incompletely characterized or unknown. We combined 5-ethynynl-2'-deoxyuridine (EdU) labeling with antibody markers that identify myenteric neuron subtypes to determine when neuron subtypes are born in the mouse small intestine. We found that different neurochemical classes of enteric neuron differed in their birthdates; serotonin neurons were born first with peak cell cycle exit at E11.5, followed by neurofilament-M neurons, calcitonin gene-related peptide neurons (peak cell cycle exit for both at embryonic day [E]12.5-E13.5), tyrosine hydroxylase neurons (E15.5), nitric oxide synthase 1 (NOS1) neurons (E15.5), and calretinin neurons (postnatal day [P]0). The vast majority of myenteric neurons had exited the cell cycle by P10. We did not observe any EdU+/NOS1+ myenteric neurons in the small intestine of adult mice following EdU injection at E10.5 or E11.5, which was unexpected, as previous studies have shown that NOS1 neurons are present in E11.5 mice. Studies using the proliferation marker Ki67 revealed that very few NOS1 neurons in the E11.5 and E12.5 gut were proliferating. However, Cre-lox-based genetic fate-mapping revealed a small subpopulation of myenteric neurons that appears to express NOS1 only transiently. Together, our results confirm a relationship between enteric neuron subtype and birthdate, and suggest that some enteric neurons exhibit neurochemical phenotypes during development that are different from their mature phenotype. Copyright © 2013 Wiley Periodicals, Inc.

Idiopathic (primary) achalasia

PubMed Central

Farrokhi, Farnoosh; Vaezi, Michael F

2007-01-01

Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES) relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg) is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram), and esophageal motility testing (esophageal manometry). Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients. PMID:17894899

[New concepts on the physiopathology, diagnosis, and treatment of achalasia].

PubMed

Carmona-Sánchez, R; Valdovinos-Díaz, M A

1998-01-01

To review the most relevant publications on the pathophysiology, clinical manifestations, diagnosis and treatment of esophageal achalasia, and the clinical experience achieved at our institution in order to propose a practical strategy to facilitate the management of these patients. Manual and MEDLINE search of key articles published between January 1986 and July 1997 in addition to publications of our institute of thirty years. All kinds of publications with substantial clinical experience, new information or research protocols. Achalasia is an uncommon disorder of the myenteric plexus of the esophagus. Main symptoms are dysphagia, regurgitations and chest pain. The diagnosis is established by manometric criteria. Esophagogram, endoscopy and radionuclide esophageal emptying test help to differentiate other conditions and evaluate the response to treatment. Pharmacotherapy may provide relief to patients with mild symptoms and is useful for patients with high risk of complications. Dilations and myotomy are safe, effective and long lasting procedures. Botulinum toxin may be effective in selected cases. Predictive factors of response have been described for each therapy. A systematic approach to the management of patients with achalasia is necessary. Introduction of new therapies as botulinum toxin and minimal invasion surgery are changing the therapeutic decisions in this field. Drugs and BoTox are considered the first line of treatment for high risk patients and dilation and surgery for patients with no risk.

Interleukin-1beta-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway.

PubMed

Wu, Z-X; Satterfield, B E; Fedan, J S; Dey, R D

2002-11-01

Interleukin (IL)-1beta causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1beta. Ferrets were instilled intratracheally with IL-1beta (0.3 microg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1beta. The IL-1beta-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1beta-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1beta. These results show that IL-1beta-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

PubMed

Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

2014-07-01

It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

VERSATILE, HIGH-RESOLUTION ANTEROGRADE LABELING OF VAGAL EFFERENT PROJECTIONS WITH DEXTRAN AMINES

PubMed Central

Walter, Gary C.; Phillips, Robert J.; Baronowsky, Elizabeth A.; Powley, Terry L.

2009-01-01

None of the anterograde tracers used to label and investigate vagal preganglionic neurons projecting to the viscera has proved optimal for routine and extensive labeling of autonomic terminal fields. To identify an alternative tracer protocol, the present experiment evaluated whether dextran conjugates, which have produced superior results in the CNS, might yield widespread and effective labeling of long, fine-caliber vagal efferents in the peripheral nervous system. The dextran conjugates that were evaluated proved reliable and versatile for labeling the motor neuron pool in its entirety, for single- and multiple-labeling protocols, for both conventional and confocal fluorescence microscopy, and for permanent labeling protocols for brightfield microscopy of the projections to the gastrointestinal (GI) tract. Using a standard ABC kit followed by visualization with DAB as the chromagen, Golgi-like labeling of the vagal efferent terminal fields in the GI wall was achieved with the biotinylated dextrans. The definition of individual terminal varicosities was so sharp and detailed that it was routinely practical to examine the relationship of putative vagal efferent contacts (by the criteria of high magnification light microscopy) with the dendritic and somatic architecture of counterstained neurons in the myenteric plexus. Overall, dextran conjugates provide high-definition labeling of an extensive vagal motor pool in the GI tract, and offer considerable versatility when multiple-staining protocols are needed to elucidate the complexities of the innervation of the gut. PMID:19056424

Serotonin or the Mucosa Do Not Mediate the Motor Effect of Allyl Isothiocyanate in the Guinea-Pig Small Intestine.

PubMed

Sandor, Zsolt I; Bencsik, Timea; Dekany, Andras; Bartho, Lorand

2016-01-01

Serotonin (5-hydroxytryptamine, 5-HT), originating from the enterochromaffin cells has been reported to mediate the contractile effect of the sensory stimulant and TRPA1 activator allyl isothiocyanate (AITC) in the guinea-pig small intestine [Nozawa et al: Proc Natl Acad Sci U S A 2009;106:3408-3413]. In the present experiments, the nerve-mediated contraction of this preparation due to AITC was not inhibited by a combination of methysergide (broad-spectrum 5-HT antagonist; 0.3 µmol/l), Y 25130 (azasetron, 5-HT3 receptor antagonist; 1 µmol/l) and SB 204070 (5-HT4 receptor antagonist; 2 µmol/l) or by 5-HT receptor desensitization, that is, pretreatments that practically abolished contractions of similar size in response to exogenous 5-HT, without causing nonspecific effects. AITC also contracted longitudinal muscle-myenteric plexus preparations, an effect also fully resistant to the combination of 5-HT receptor antagonists. The pharmacology of AITC in strip preparations matched that in the whole ileum. Key Messages: It is concluded that neither endogenous 5-HT nor the gut mucosa contributes to the excitatory effect of AITC in the guinea-pig small intestine. The combination of 5-HT antagonists elaborated is suitable for studying the possible involvement of 5-HT in motor responses of the guinea-pig intestine. © 2016 S. Karger AG, Basel.

The role of colonic mast cells and myenteric plexitis in patients with diverticular disease.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Nascimbeni, Riccardo; Antonelli, Elisabetta; Cadei, Moris; Manenti, Stefania; Lorenzi, Luisa; Titi, Amin; Salerni, Bruno

2013-02-01

Gut mast cells represent an important cell population involved in intestinal homeostasis and inflammatory processes. However, their possible role has not to date been investigated in colonic diverticular disease. This study aims to evaluate colonic mast cells in patients undergoing surgery for diverticular disease. Surgical resection samples from 27 patients undergoing surgery for diverticular disease (12 emergency procedures for severe disease and 15 elective procedures) were evaluated. The number of mast cells was assessed in the various layers by means of a specific antibody (tryptase) and compared with those evaluated in ten controls. In patients with mast cells degranulation, double immunohistochemistry, also assessing nerve fibres, was carried out. In addition, the presence of myenteric plexitis was sought. Compared with controls, the number of mast cells in diverticular patients was significantly increased, both as an overall figure and in the various layers of the large bowel. In patients in whom mast cells degranulation was present, these were always closed to nerve fibres. No differences were found between the two subgroups of patients with respect to the number and distribution of mast cells; however, all patients undergoing emergency surgery (but none of those undergoing elective procedures) had myenteric plexitis, represented by lymphocytic infiltration in 67 % and eosinophilic infiltration in 33 % of cases. Patients with diverticular disease display an increase of mast cells in the large bowel. The presence of myenteric plexitis in those with complicated, severe disease, suggest that this could represent a histopathologic marker of more aggressive disease.

Impaired insulin/IGF-1 is responsible for diabetic gastroparesis by damaging myenteric cholinergic neurones and interstitial cells of Cajal.

PubMed

Yang, Shu; Wu, Bo; Sun, Haimei; Sun, Tingyi; Han, Kai; Li, Dandan; Ji, Fengqing; Zhang, Guoquan; Zhou, Deshan

2017-10-31

Diabetic gastroparesis is a common complication of diabetes mellitus (DM) that is characterized by decreased serum insulin and insulin-like growth factor-1 (IGF-1). Despite the fact that insulin treatment not glycemic control potently accelerated gastric emptying in type 1 DM patients, the role of insulin/InsR and IGF-1/IGF-1R signaling in diabetic gastroparesis remains incompletely elucidated. In the present study, type 1 DM mice were established and treated with insulin or Voglibose for 8 weeks. The gastric emptying was delayed from DM week 4 when the gastric InsR and IGF-1R were declined. Meanwhile, the gastric choline acetyltransferase (ChAT) was significantly reduced and the myenteric cholinergic neurones and their fibers were significantly diminished. The production of stem cell factor (SCF) was dramatically repressed in the gastric smooth muscles in DM week 6. TWereafter, interstitial cells of Cajal (ICC) were clearly lost and their networks were impaired in DM week 8. Significantly, compared with Voglibose, an 8-week treatment with insulin more efficiently delayed diabetic gastroparesis development by protecting the myenteric cholinergic neurones and ICC. In conclusion, diabetic gastroparesis was an aggressive process due to the successive damages of myenteric cholinergic neurones and ICC by impairing the insulin/InsR and IGF-1/IGF-1R signaling. Insulin therapy in the early stage may delay diabetic gastroparesis. © 2017 The Author(s).

Insights into the mechanisms underlying colonic motor patterns

PubMed Central

Dinning, Phil G.; Brookes, Simon J.; Costa, Marcello

2016-01-01

Abstract In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID:26990133

New insights into the pathophysiology of achalasia and implications for future treatment.

PubMed

Furuzawa-Carballeda, Janette; Torres-Landa, Samuel; Valdovinos, Miguel Ángel; Coss-Adame, Enrique; Martín Del Campo, Luis A; Torres-Villalobos, Gonzalo

2016-09-21

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.

New insights into the pathophysiology of achalasia and implications for future treatment

PubMed Central

Furuzawa-Carballeda, Janette; Torres-Landa, Samuel; Valdovinos, Miguel Ángel; Coss-Adame, Enrique; Martín del Campo, Luis A; Torres-Villalobos, Gonzalo

2016-01-01

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient’s quality of life. PMID:27672286

Botulinum toxin type A inhibits rat pyloric myoelectrical activity and substance P release in vivo.

PubMed

Hou, Yi-Ping; Zhang, Yong-Ping; Song, Yan-Feng; Zhu, Chun-Min; Wang, Yin-Chun; Xie, Gui-Lin

2007-02-01

The effect of botulinum toxin type A (BTX-A) on rat pyloric myoelectrical activity in vivo and the content and distribution of substance P (SP) in pylorus were investigated, respectively, with electromyography, radioimmunoassay, and immunohistochemistry. A pair of electrodes for recording pyloric myoelectrical activity and a guide cannula for drug injection were implanted into the pylorus. The changes of pyloric myoelectrical activity were recorded followed vehicle, 10, 20, and 40 U/kg body mass of BTX-A injection. Pyloric tissues were dissected for radioimmunoassay and immunohistochemistry after recording. The 3 dosages of BTX-A injections caused the reduction of slow wave of pyloric myoelectrical activity in amplitude but not in frequency and the diminishment of spike activity in amplitude and spike burst. The inhibitory effect of 20 U/kg BTX-A was significantly different from that of 10 U/kg (p<0.05), but not from the effect of 40 U/kg administration (p>0.05). After BTX-A intrasphincteric injection, SP content was reduced in the pylorus, and cell number of SP-immunoreactivity was decreased more in myenteric nerve plexus of circular muscle and in mucosa of pylori. In conclusion, BTX-A inhibits pyloric myoelectrical slow activity in amplitude and spike activity and weakens pyloric smooth muscle contractility depending on threshold of dose or concentration. BTX-A-induced inhibition of pyloric myoelectrical activity implies a mechanism of inhibiting SP release from the autonomic and enteric nervous terminals in the pylorus.

Design, synthesis and structure-activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression.

PubMed

Mahesh, Radhakrishnan; Devadoss, Thangaraj; Pandey, Dilip Kumar; Bhatt, Shvetank; Yadav, Shushil Kumar

2010-11-15

A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds' structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT(3) receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methyl-5-HT, which was expressed in the form of pA(2) value. All the synthesized compounds showed antagonism towards 5-HT(3) receptor; based on this result, a structure-activity relationship was derived, which reveals that the aromatic residue in 5-HT(3) receptor antagonists may have hydrophobic interaction with 5-HT(3) receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA(2) values exhibited good anti-depressant-like activity as compared to the vehicle-treated group. Copyright © 2010 Elsevier Ltd. All rights reserved.

Telocytes in Crohn’s disease

PubMed Central

Milia, Anna Franca; Ruffo, Martina; Manetti, Mirko; Rosa, Irene; Conte, Dalila; Fazi, Marilena; Messerini, Luca; Ibba-Manneschi, Lidia

2013-01-01

Crohn’s disease (CD) is a relapsing chronic inflammatory disorder that may involve all the gastrointestinal tract with a prevalence of terminal ileum. Intestinal lesions have a characteristic discontinuous and segmental distribution and may affect all layers of the gut wall. Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including gastrointestinal tract of humans and mammals. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility. The aim of our study was to investigate the presence and distribution of TC in disease-affected and -unaffected ileal specimens from CD patients compared with controls. TC were identified by CD34/PDGFRα immunohistochemistry. In affected CD specimens TC disappeared, particularly where fibrosis and architectural derangement of the intestinal wall were observed. In the thickened muscularis mucosae and submucosa, few TC entrapped in the fibrotic extracellular matrix were found. A discontinuous network of TC was present around smooth muscle bundles, ganglia and enteric strands in the altered muscularis propria. At the myenteric plexus, the loss of TC network was paralleled by the loss of interstitial cells of Cajal network. In the unaffected CD specimens, TC were preserved in their distribution. Our results suggest that in CD the loss of TC might have important pathophysiological implications contributing to the architectural derangement of the intestinal wall and gut dysmotility. Further functional studies are necessary to better clarify the role of TC loss in CD pathophysiology. PMID:24251911

Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet.

PubMed

Rivera, L R; Leung, C; Pustovit, R V; Hunne, B L; Andrikopoulos, S; Herath, C; Testro, A; Angus, P W; Furness, J B

2014-08-01

Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes. Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons. The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium. Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease. © 2014 John Wiley & Sons Ltd.

Changes in membrane cholesterol affect caveolin-1 localization and ICC-pacing in mouse jejunum.

PubMed

Daniel, E E; Bodie, Gregory; Mannarino, Marco; Boddy, Geoffrey; Cho, Woo-Jung

2004-07-01

Pacing of mouse is dependent on the spontaneous activity of interstitial cells of Cajal in the myenteric plexus (ICC-MP). These ICC, as well as intestinal smooth muscle, contain small membrane invaginations called caveolae. Caveolae are signaling centers formed by insertions of caveolin proteins in the inner aspect of the plasma membrane. Caveolins bind signaling proteins and thereby negatively modulate their signaling. We disrupted caveolae by treating intestinal segments with methyl beta-clodextrin (CD) to remove cholesterol or with water-soluble cholesterol (WSC) to load cholesterol. Both of these treatments reduced pacing frequencies, and these effects were reversed by the other agent. These treatments also inhibited paced contractions, but complete reversal was not observed. To evaluate the specificity of the effects of CD and WSC, additional studies were made of their effects on responses to carbamoyl choline and to stimulation of cholinergic nerves. Neither of these treatments affected these sets of responses compared with their respective time controls. Immunochemical and ultrastructural studies showed that caveolin 1 was present in smooth muscle membranes and ICC-MP. CD depleted both caveolin 1 and caveolae, whereas WSC increased the amount of caveolin 1 immunoreactivity and altered its distribution but failed to increase the number of caveolae. The effects of each agent were reversed in major part by the other. We conclude that signaling through caveolae may play a role in pacing by ICC but does not affect responses to acetylcholine from nerves or when added exogenously.

Progression of choroid plexus papilloma.

PubMed

Dhillon, Rana S; Wang, Yi Yuen; McKelvie, Penny A; O'Brien, Brendan

2013-12-01

Choroid plexus papillomas are rare neoplasms that arise from choroid plexus epithelium. The World Health Organization classification describes three histological grades. Grade I is choroid plexus papilloma, grade II is atypical choroid plexus papilloma and grade III is choroid plexus carcinoma. Progression between grades is rare but documented. We present two adult cases, a 53-year-old female and a 70-year-old male, who demonstrated clear interval histological progression from grade I choroid plexus papilloma to higher grades. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of oxaliplatin on mouse myenteric neurons and colonic motility

PubMed Central

Wafai, Linah; Taher, Mohammadali; Jovanovska, Valentina; Bornstein, Joel C.; Dass, Crispin R.; Nurgali, Kulmira

2013-01-01

Oxaliplatin, an anti-cancer chemotherapeutic agent used for the treatment of colorectal cancer, commonly causes gastrointestinal side-effects such as constipation, diarrhoea, nausea, and vomiting. Damage to enteric neurons may underlie some of these gastrointestinal side-effects, as the enteric nervous system (ENS) controls functions of the bowel. In this study, neuronal loss and changes to the structure and immunoreactivity of myenteric neuronal nitric oxide synthase (nNOS) neurons were examined in colonic segments from mice following exposure to oxaliplatin ex vivo and following repeated intraperitoneal injections of oxaliplatin over 3 weeks in vivo, using immunohistochemistry and confocal microscopy. Significant morphological alterations and increases in the proportion of NOS-immunoreactive (IR) neurons were associated with both short-term oxaliplatin exposure and long-term oxaliplatin administration, confirming that oxaliplatin causes changes to the myenteric neurons. Long-term oxaliplatin administration induced substantial neuronal loss that was correlated with a reduction in both the frequency and propagation speed of colonic migrating motor complexes (CMMCs) in vitro. Similar changes probably produce some symptoms experienced by patients undergoing oxaliplatin treatment. PMID:23486839

Neurochemical coding of enteric neurons in the guinea pig stomach.

PubMed

Schemann, M; Schaaf, C; Mäder, M

1995-03-06

The aim of this study was to investigate the neurochemical coding of myenteric neurons in the guinea pig gastric corpus by using immunohistochemical methods. Antibodies and antisera against calbindin (CALB), calretinin (CALRET), choline acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP), dopamine beta-hydroxylase (DBH), beta-endorphin (ENK), neuropeptide Y (NPY), neuron-specific enolase (NSE), nitric oxide synthase (NOS), protein gene product 9.5 (PGP), parvalbumin (PARV), serotonin (5-HT), somatostatin (SOM), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. Double- and triple-labeling studies revealed colocalization of certain transmitters and enabled the identification of distinct subpopulations of gastric enteric neurons. NPY/VIP/NOS/ENK were present in 28% of all neurons, whereas 11% had NPY/VIP/DBH/ChAT; NOS-only neurons made up 2% of the population. The combination SP/ChAT/ENK occurred in 21% of the population, whereas SP/ChAT/ENK/CALRET and SP/CHAT/SOM/ +/- CALRET was identified in 5% and 6% of all cells, respectively. 5-HT-containing neurons comprised 2% of all cells and could be further classified by the presence of additional antigens as 5-HT/SP/(ChAT) or 5-HT/VIP/(ChAT). Approximately 21% of all neurons contained only ChAT with no additional antigen present and are referred to as ChAT/-. Gastric myenteric ganglion cells were not immunoreactive for CALB, PARV, CGRP, or TH. The results of this study indicate that gastric myenteric neurons can be characterized on the basis of different chemical coding. Neurochemical coding of corpus myenteric neurons revealed some similarities and significant differences in comparison with other regions of the gut. These differences might reflect adaptation of enteric nerves according to regional specialization and the distinct functions of the proximal stomach as a gastric reservoir.

The Macroanatomy of the Sacral Plexus and Its Nerves in Eurasian Eagle Owls (Bubo bubo).

PubMed

Akbulut, Y; Demiraslan, Y; Aslan, K; Coban, A

2016-10-01

This study was carried out to reveal the formation of the sacral plexus in the Eurasian Eagle Owls (Bubo bubo) and the nerves originating from this plexus. Five EEOs, three of them were male and two were female, were provided from Wildlife Rescue and Rehabilitation Center of Kafkas University and used as materials. Following the euthanizing of the animals, abdominal cavity was opened. The nerves of plexus sacrales were dissected and photographed. It was detected that the sacral plexus was formed by the ventral ramus of five synsacral nerves. Moreover, it was determined that the roots of the sacral plexus formed three trunks: the truncus cranialis, the truncus medius and the truncus caudalis in fossa renalis. The availability of the n. ischiofemoralis and the availability of n. parafibularis were detected in the EEOs. Five branches were specified as having segregated from the sacral plexus: the n. cutaneus femoralis caudalis, the mutual root of n. fibularis with n. tibialis (n. ischiadicus), the rami musculares, the n. coxalis caudalis and the ramus muscularis. It was observed that the sacral plexus was linked to the lumbar plexus by the n. furcalis, to the pudendus plexus via the n. bigeminus. Consequently, the anatomic structure of the EEO's sacral plexus, the participating synsacral nerves to plexus and the innervation areas of these nerves were revealed. © 2015 Blackwell Verlag GmbH.

Posterior subscapular dissection: An improved approach to the brachial plexus for human anatomy students.

PubMed

Hager, Shaun; Backus, Timothy Charles; Futterman, Bennett; Solounias, Nikos; Mihlbachler, Matthew C

2014-05-01

Students of human anatomy are required to understand the brachial plexus, from the proximal roots extending from spinal nerves C5 through T1, to the distal-most branches that innervate the shoulder and upper limb. However, in human cadaver dissection labs, students are often instructed to dissect the brachial plexus using an antero-axillary approach that incompletely exposes the brachial plexus. This approach readily exposes the distal segments of the brachial plexus but exposure of proximal and posterior segments require extensive dissection of neck and shoulder structures. Therefore, the proximal and posterior segments of the brachial plexus, including the roots, trunks, divisions, posterior cord and proximally branching peripheral nerves often remain unobserved during study of the cadaveric shoulder and brachial plexus. Here we introduce a subscapular approach that exposes the entire brachial plexus, with minimal amount of dissection or destruction of surrounding structures. Lateral retraction of the scapula reveals the entire length of the brachial plexus in the subscapular space, exposing the brachial plexus roots and other proximal segments. Combining the subscapular approach with the traditional antero-axillary approach allows students to observe the cadaveric brachial plexus in its entirety. Exposure of the brachial dissection in the subscapular space requires little time and is easily incorporated into a preexisting anatomy lab curriculum without scheduling additional time for dissection. Copyright © 2014 Elsevier GmbH. All rights reserved.

Pathogenesis of achalasia cardia.

PubMed

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-06-28

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

Pathogenesis of achalasia cardia

PubMed Central

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-01-01

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus. PMID:22791940

Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

PubMed Central

Kwon, Yong Hwan; Kim, Nayoung; Nam, Ryoung Hee; Park, Ji Hyun; Lee, Sun Min; Kim, Sung Kook; Lee, Hye Seung; Kim, Yong Sung; Lee, Dong Ho

2017-01-01

The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age. PMID:28045993

Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winbery, S.L.; Barker, L.A.

1986-03-01

The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to allmore » doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.« less

Ca2+ Responses in Enteric Glia are Mediated by Connexin-43 Hemichannels and Modulate Colonic Transit in Mice

PubMed Central

Fried, David; Gomez-Suarez, Roberto A.; Leinninger, Gina M.; Sévigny, Jean; Parpura, Vladimir; Gulbransen, Brian D.

2014-01-01

Background & Aims In the enteric nervous system, neurotransmitters initiate changes in Ca2+ (Ca2+ responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca2+-mediated responses in enteric glial are required to maintain gastrointestinal function. Methods We used in situ Ca2+ imaging to monitor glial Ca2+ responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::creERT2+/−/Cx43f/f mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription PCR analyses. Results Ca2+ responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca2+ responses. In vivo attenuation of Ca2+ responses in the enteric glial network slowed gut transit overall and delayed colonic transit—these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca2+-mediated responses and changes in glial expression of Cx43 mRNA and protein. Conclusions Ca2+-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders. PMID:24211490

Proteolytic inactivation of substance P and neurokinin A in the longitudinal muscle layer of guinea pig small intestine.

PubMed

Nau, R; Schäfer, G; Deacon, C F; Cole, T; Agoston, D V; Conlon, J M

1986-09-01

Membrane vesicles, showing a 21 +/- 2-fold enrichment in the activity of 5'-nucleotidase and a 11 +/- 4-fold enrichment in the activity of angiotensin-converting enzyme relative to homogenate, were prepared from the myenteric plexus-containing longitudinal muscle layer of guinea pig ileum. Incubation of the vesicles with substance P and neurokinin A led to degradation of the peptides, and metabolites were isolated by reverse-phase HPLC and identified by amino acid composition. Cleavages of substance P between Glu6-Phe7, Phe7-Phe8, and Gly9-Leu10 and of neurokinin A between Gly8-Leu9 were observed and could be inhibited in a dose-dependent manner by phosphoramidon, an inhibitor of neutral endopeptidase 24.11. Formation of these metabolites was not completely inhibited by this agent, indicating that a phosphoramidon-insensitive form of endopeptidase 24.11 was present in the gut. Substance P was resistant to degradation by aminopeptidases, but neurokinin A was a substrate for bestatin-sensitive aminopeptidase(s), so that the neurokinin A (3-10) fragment represented the predominant metabolite in the chromatograms. The rate of formation of all the metabolites was not inhibited by enalapril and not enhanced by an increased Cl- concentration, indicating that angiotensin-converting enzyme was unimportant in the degradation process. Degradation of neurokinin A by the vesicles (Km 30 microM; Vmax 7.2 +/- 0.8 nmol min-1 mg of protein-1) was more rapid than degradation of substance P (Km 25 microM; Vmax 4.4 +/- 0.4 nmol min-1 mg of protein-1).

Per rectal endoscopic myotomy for the treatment of adult Hirschsprung's disease: First human case (with video).

PubMed

Bapaye, Amol; Wagholikar, Gajanan; Jog, Sameer; Kothurkar, Aditi; Purandare, Shefali; Dubale, Nachiket; Pujari, Rajendra; Mahadik, Mahesh; Vyas, Viral; Bapaye, Jay

2016-09-01

Hirschsprung's disease (HD) is a congenital disorder characterized by the absence of intrinsic ganglion cells in submucosal and myenteric plexuses of the hindgut; and presents with constipation, intestinal obstruction and/or megacolon. HD commonly involves the rectosigmoid region (short segment HD), although shorter and longer variants of the disease are described. Standard treatment involves pull-through surgery for short segment HD or posterior anorectal myotomy in selected ultrashort segment candidates. Third space endoscopy has evolved during the past few years. Per oral endoscopic myotomy and per oral pyloromyotomy are described for treatment of achalasia cardia and refractory gastroparesis, respectively. Using the same philosophy of muscle/sphincter disruption for spastic bowel segments, per rectal endoscopic myotomy could be considered as a treatment option for short segment HD. A 24-year-old male patient presented with refractory constipation since childhood, and habituated to high-dose laxative combinations. Diagnosis was confirmed as adult short segment HD by barium enema, colonoscopic deep suction mucosal biopsies and anorectal manometry. Histopathology confirmed aganglionosis in the distal 15 cm. By implementing principles of third space endoscopy, per rectal endoscopic myotomy 20 cm in length was successfully carried out. At 24-week follow up, the patient reported significant relief of constipation and associated symptoms. Sigmoidoscopy, anorectal manometry and barium enema confirm improved rectal distensibility and reduced rectal pressures. The present case report describes the first human experience of per rectal endoscopic myotomy for successful treatment of adult short segment HD. © 2016 Japan Gastroenterological Endoscopy Society.

Morphological patterns in children with ganglion related enteric neuronal abnormalities.

PubMed

Henna, Nausheen; Nagi, Abdul H; Sheikh, Muhammad A; Shaukat, Mahmood

2011-01-01

Hirschsprung's Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissner's) and myenteric (Aurbach's) plexuses of distal bowel. The purpose of the present study was to observe and report the morphological patterns of ganglion related enteric neuronal abnormalities in children presented with clinical features of (HD) in a Pakistani population. A total of 92 patients with clinical presentation of HD were enrolled between March 2009 and October 2009. Among them, 8 were excluded according to the exclusion criteria. After detailed history and physical examination, paraffin embedded H and E stained sections were prepared from the serial open biopsies from colorectum. The data was analysed using SPSS-17. Frequencies and percentages are given for qualitative variables. Non-parametric Binomial Chi-Square test was applied to observe within group associations and p<0.05 was considered statistically significant. Among 84 patients, 13 (15.5%) proved to be normally ganglionic whereas 71 (84.5%) showed ganglion related enteric neuronal abnormalities namely isolated hypoganglionosis 9 (12.7%), immaturity of ganglion cells 9 (12.7%), isolated hyperganglionosis (IND Type B) 2 (2.8%) and Hirschsprung's disease 51 (71.8%). Among HD group, 34 (66.7%) belonged to isolated form and 17 (33.3%) showed combined ganglion related abnormalities. Hirschsprung's disease is common in Pakistani population, followed by hypoganglionosis, immaturity of ganglion cells and IND type B. The presence of hypertrophic nerve fibres was significant in HD, hyperganglionosis and hypoganglionosis, whereas, no hypertrophic nerve fibres were appreciated in immaturity of ganglion cell group.

Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

PubMed

Prendergast, Nicole; Goldstein, Jeffrey D; Beier, Alexandra D

2018-04-01

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Clinical anatomy and 3D virtual reconstruction of the lumbar plexus with respect to lumbar surgery.

PubMed

Lu, Sheng; Chang, Shan; Zhang, Yuan-zhi; Ding, Zi-hai; Xu, Xin Ming; Xu, Yong-qing

2011-04-14

Exposure of the anterior or lateral lumbar via the retroperitoneal approach easily causes injuries to the lumbar plexus. Lumbar plexus injuries which occur during anterior or transpsoas lumbar spine exposure and placement of instruments have been reported. This study aims is to provide more anatomical data and surgical landmarks in operations concerning the lumbar plexus in order to prevent lumbar plexus injuries and to increase the possibility of safety in anterior approach lumbar surgery. To study the applied anatomy related to the lumbar plexus of fifteen formaldehyde-preserved cadavers, Five sets of Virtual Human (VH) data set were prepared and used in the study. Three-dimensional (3D) computerized reconstructions of the lumbar plexus and their adjacent structures were conducted from the VH female data set. The order of lumbar nerves is regular. From the anterior view, lumbar plexus nerves are arranged from medial at L5 to lateral at L2. From the lateral view, lumbar nerves are arranged from ventral at L2 to dorsal at L5. The angle of each nerve root exiting outward to the corresponding intervertebral foramen increases from L1 to L5. The lumbar plexus nerves are observed to be in close contact with transverse processes (TP). All parts of the lumbar plexus were located by sectional anatomy in the dorsal third of the psoas muscle. Thus, access to the psoas major muscle at the ventral 2/3 region can safely prevent nerve injuries. 3D reconstruction of the lumbar plexus based on VCH data can clearly show the relationships between the lumbar plexus and the blood vessels, vertebral body, kidney, and psoas muscle. The psoas muscle can be considered as a surgical landmark since incision at the ventral 2/3 of the region can prevent lumbar plexus injuries for procedures requiring exposure of the lateral anterior of the lumbar. The transverse process can be considered as a landmark and reference in surgical operations by its relative position to the lumbar plexus. 3D reconstructions of the lumbar plexus based on VCH data provide a virtual morphological basis for anterior lumbar surgery.

Clinical anatomy and 3D virtual reconstruction of the lumbar plexus with respect to lumbar surgery

PubMed Central

2011-01-01

Background Exposure of the anterior or lateral lumbar via the retroperitoneal approach easily causes injuries to the lumbar plexus. Lumbar plexus injuries which occur during anterior or transpsoas lumbar spine exposure and placement of instruments have been reported. This study aims is to provide more anatomical data and surgical landmarks in operations concerning the lumbar plexus in order to prevent lumbar plexus injuries and to increase the possibility of safety in anterior approach lumbar surgery. Methods To study the applied anatomy related to the lumbar plexus of fifteen formaldehyde-preserved cadavers, Five sets of Virtual Human (VH) data set were prepared and used in the study. Three-dimensional (3D) computerized reconstructions of the lumbar plexus and their adjacent structures were conducted from the VH female data set. Results The order of lumbar nerves is regular. From the anterior view, lumbar plexus nerves are arranged from medial at L5 to lateral at L2. From the lateral view, lumbar nerves are arranged from ventral at L2 to dorsal at L5. The angle of each nerve root exiting outward to the corresponding intervertebral foramen increases from L1 to L5. The lumbar plexus nerves are observed to be in close contact with transverse processes (TP). All parts of the lumbar plexus were located by sectional anatomy in the dorsal third of the psoas muscle. Thus, access to the psoas major muscle at the ventral 2/3 region can safely prevent nerve injuries. 3D reconstruction of the lumbar plexus based on VCH data can clearly show the relationships between the lumbar plexus and the blood vessels, vertebral body, kidney, and psoas muscle. Conclusion The psoas muscle can be considered as a surgical landmark since incision at the ventral 2/3 of the region can prevent lumbar plexus injuries for procedures requiring exposure of the lateral anterior of the lumbar. The transverse process can be considered as a landmark and reference in surgical operations by its relative position to the lumbar plexus. 3D reconstructions of the lumbar plexus based on VCH data provide a virtual morphological basis for anterior lumbar surgery. PMID:21492461

Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica

PubMed Central

2010-01-01

Background Choroid plexus epithelial cells are the site of blood/cerebrospinal fluid (CSF) barrier and regulate molecular transfer between the two compartments. Their mitotic activity in the adult is low. During development, the pattern of growth and timing of acquisition of functional properties of plexus epithelium are not known. Methods Numbers and size of choroid plexus epithelial cells and their nuclei were counted and measured in the lateral ventricular plexus from the first day of its appearance until adulthood. Newborn Monodelphis pups were injected with 5-bromo-2-deoxyuridine (BrdU) at postnatal day 3 (P3), P4 and P5. Additional animals were injected at P63, P64 and P65. BrdU-immunopositive nuclei were counted and their position mapped in the plexus structure at different ages after injections. Double-labelling immunocytochemistry with antibodies to plasma protein identified post-mitotic cells involved in protein transfer. Results Numbers of choroid plexus epithelial cells increased 10-fold between the time of birth and adulthood. In newborn pups each consecutive injection of BrdU labelled 20-40 of epithelial cells counted. After 3 injections, numbers of BrdU positive cells remained constant for at least 2 months. BrdU injections at an older age (P63, P64, P65) resulted in a smaller number of labelled plexus cells. Numbers of plexus cells immunopositive for both BrdU and plasma protein increased with age indicating that protein transferring properties are acquired post mitotically. Labelled nuclei were only detected on the dorsal arm of the plexus as it grows from the neuroependyma, moving along the structure in a 'conveyor belt' like fashion. Conclusions The present study established that lateral ventricular choroid plexus epithelial cells are born on the dorsal side of the structure only. Cells born in the first few days after choroid plexus differentiation from the neuroependyma remain present even two months later. Protein-transferring properties are acquired post-mitotically and relatively early in plexus development. PMID:20920364

Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica.

PubMed

Liddelow, Shane A; Dziegielewska, Katarzyna M; Vandeberg, John L; Saunders, Norman R

2010-10-05

Choroid plexus epithelial cells are the site of blood/cerebrospinal fluid (CSF) barrier and regulate molecular transfer between the two compartments. Their mitotic activity in the adult is low. During development, the pattern of growth and timing of acquisition of functional properties of plexus epithelium are not known. Numbers and size of choroid plexus epithelial cells and their nuclei were counted and measured in the lateral ventricular plexus from the first day of its appearance until adulthood. Newborn Monodelphis pups were injected with 5-bromo-2-deoxyuridine (BrdU) at postnatal day 3 (P3), P4 and P5. Additional animals were injected at P63, P64 and P65. BrdU-immunopositive nuclei were counted and their position mapped in the plexus structure at different ages after injections. Double-labelling immunocytochemistry with antibodies to plasma protein identified post-mitotic cells involved in protein transfer. Numbers of choroid plexus epithelial cells increased 10-fold between the time of birth and adulthood. In newborn pups each consecutive injection of BrdU labelled 20-40 of epithelial cells counted. After 3 injections, numbers of BrdU positive cells remained constant for at least 2 months. BrdU injections at an older age (P63, P64, P65) resulted in a smaller number of labelled plexus cells. Numbers of plexus cells immunopositive for both BrdU and plasma protein increased with age indicating that protein transferring properties are acquired post mitotically. Labelled nuclei were only detected on the dorsal arm of the plexus as it grows from the neuroependyma, moving along the structure in a 'conveyor belt' like fashion. The present study established that lateral ventricular choroid plexus epithelial cells are born on the dorsal side of the structure only. Cells born in the first few days after choroid plexus differentiation from the neuroependyma remain present even two months later. Protein-transferring properties are acquired post-mitotically and relatively early in plexus development.

Child neurology: Brachial plexus birth injury: what every neurologist needs to know.

PubMed

Pham, Christina B; Kratz, Johannes R; Jelin, Angie C; Gelfand, Amy A

2011-08-16

While most often transient, brachial plexus birth injury can cause permanent neurologic injury. The major risk factors for brachial plexus birth injury are fetal macrosomia and shoulder dystocia. The degree of injury to the brachial plexus should be determined in the neonatal nursery, as those infants with the most severe injury--root avulsion--should be referred early for surgical evaluation so that microsurgical repair of the plexus can occur by 3 months of life. Microsurgical repair options include nerve grafts and nerve transfers. All children with brachial plexus birth injury require ongoing physical and occupational therapy and close follow-up to monitor progress.

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer's disease.

PubMed

Bolos, Marta; Spuch, Carlos; Ordoñez-Gutierrez, Lara; Wandosell, Francisco; Ferrer, Isidro; Carro, Eva

2013-08-01

β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer's disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer's disease.

Evaluation of an education day for families of children with obstetrical brachial plexus palsy.

PubMed

Ho, Emily S; Ulster, Alissa A

2011-09-01

Children with obstetrical brachial plexus palsy may have chronic physical impairment in their affected upper extremity. Affected children and their families may benefit from psychosocial interventions including therapeutic relationships with health professionals, meeting other families living with obstetrical brachial plexus palsy, support groups, and social work. One method of addressing psychosocial needs is through a support and education day. The purpose of this quality improvement project is to evaluate parental perceptions of a support and education day called the "Brachial Plexus Family Day." Families of children with obstetrical brachial plexus palsy who attended the Brachial Plexus Family Day completed a questionnaire to evaluate the different programs offered during the day. The families also ranked the importance of different psychosocial supports offered in the clinic. Sixty-three out of 69 families completed the questionnaire. Each program of the Brachial Plexus Family Day was rated as good or excellent by the respondents. Ninety-seven percent of respondents rated meeting other families and children with obstetrical brachial plexus palsy as helpful supports. Attending a Brachial Plexus Family day event (86%), followed by connecting with a doctor (60%), and physical or occupational therapist (59%) were the highest ranked supports reported by the families. The parents and caregivers that attended the Brachial Plexus Family Day rated the program highly. This group also valued the opportunity to connect with other families and children affected with the same condition.

Clinical research of comprehensive rehabilitation in treating brachial plexus injury patients.

PubMed

Zhou, Jun-Ming; Gu, Yu-Dong; Xu, Xiao-Jun; Zhang, Shen-Yu; Zhao, Xin

2012-07-01

Brachial plexus injury is one of the difficult medical problems in the world. The aim of this study was to observe the clinical therapeutic effect of comprehensive rehabilitation in treating dysfunction after brachial plexus injury. Forty-three cases of dysfunction after brachial plexus injury were divided into two groups randomly. The treatment group, which totaled 21 patients (including 14 cases of total brachial plexus injury and seven cases of branch brachial plexus injury), was treated with comprehensive rehabilitation including transcutaneous electrical nerve stimulation, mid-frequency electrotherapy, Tuina therapy, and occupational therapy. The control group, which totaled 22 patients (including 16 cases of total brachial plexus injury and six cases of branch brachial plexus injury), was treated with home-based electrical nerve stimulation and occupational therapy. Each course was of 30 days duration and the patients received four courses totally. After four courses, the rehabilitation effect was evaluated according to the brachial plexus function evaluation standard and electromyogram (EMG) assessment. In the treatment group, there was significant difference in the scores of brachial plexus function pre- and post-treatment (P < 0.01) in both "total" and "branch" injury. The scores of two "total injury" groups had statistical differences (P < 0.01), while the scores of two "branch injury" groups had statistical differences (P < 0.05) after four courses. EMG suggested that the appearance of regeneration potentials of the recipient nerves in the treatment group was earlier than the control group and had significant differences (P < 0.05). Comprehensive rehabilitation was more effective in treating dysfunction after brachial plexus injury than nonintegrated rehabilitation.

Encephalitis, proventricular and ventricular myositis, and myenteric ganglioneuritis in an umbrella cockatoo.

PubMed

Joyner, K L; Kock, N; Styles, D

1989-01-01

Myenteric ganglioneuritis and encephalomyelitis were diagnosed in an umbrella cockatoo. The cockatoo exhibited clinical signs that were milder than those associated with this syndrome, such as anorexia, muscle wasting, regurgitation, depression, and changes in fecal consistency. The gross lesions also differed from earlier reports in that only the duodenum and proximal jejunum were grossly dilated. Normally the proventriculus and ventriculus are dilated without visible intestinal changes. The histopathological lesions, however, such as perivascular cuffs in the brain stem and muscular mass of the ventriculus and proventriculus, were similar to earlier reports. A virus was suspected, although transmission and isolation of a virus has not occurred in other reports and was not attempted in this case.

Surgical anesthesia with a combination of T12 paravertebral block and lumbar plexus, sacral plexus block for hip replacement in ankylosing spondylitis: CARE-compliant 4 case reports.

PubMed

Ke, Xijian; Li, Ji; Liu, Yong; Wu, Xi; Mei, Wei

2017-06-26

Anesthesia management for patients with severe ankylosing spondylitis scheduled for total hip arthroplasty is challenging due to a potential difficult airway and difficult neuraxial block. We report 4 cases with ankylosing spondylitis successfully managed with a combination of lumbar plexus, sacral plexus and T12 paravertebral block. Four patients were scheduled for total hip arthroplasty. All of them were diagnosed as severe ankylosing spondylitis with rigidity and immobilization of cervical and lumbar spine and hip joints. A combination of T12 paravertebral block, lumbar plexus and sacral plexus block was successfully used for the surgery without any additional intravenous anesthetic or local anesthetics infiltration to the incision, and none of the patients complained of discomfort during the operations. The combination of T12 paravertebral block, lumbar plexus and sacral plexus block, which may block all nerves innervating the articular capsule, surrounding muscles and the skin involved in total hip arthroplasty, might be a promising alternative for total hip arthroplasty in ankylosing spondylitis.

Transport across the choroid plexus epithelium.

PubMed

Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

Synaptic activation of putative sensory neurons by hexamethonium-sensitive nerve pathways in mouse colon.

PubMed

Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Brookes, Simon J H; Hu, Hongzhen; Keating, Damien J; Spencer, Nick J

2018-01-01

The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene-related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Whether this is observed using different recording techniques is of particular interest for understanding the physiology of these neurons and neural circuit modeling. Here, we imaged spontaneous and evoked activation of myenteric neurons in isolated whole preparations of mouse colon and correlated recordings with CGRP and nitric oxide synthase (NOS) immunoreactivity, post hoc. Calcium indicator fluo 4 was used for this purpose. Calcium responses were recorded in nerve cell bodies located 5-10 mm oral to transmural electrical nerve stimuli. A total of 618 recorded neurons were classified for CGRP or NOS immunoreactivity. Aboral electrical stimulation evoked short-latency calcium transients in the majority of myenteric neurons, including ~90% of CGRP-immunoreactive Dogiel type II neurons. Activation of Dogiel type II neurons had a time course consistent with fast synaptic transmission and was always abolished by hexamethonium (300 μM) and by low-calcium Krebs solution. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (during synaptic blockade) directly activated Dogiel type II neurons. The present study suggests that murine colonic Dogiel type II neurons receive prominent fast excitatory synaptic inputs from hexamethonium-sensitive neural pathways. NEW & NOTEWORTHY Myenteric neurons in isolated mouse colon were recorded using calcium imaging and then neurochemically defined. Short-latency calcium transients were detected in >90% of calcitonin gene-related peptide-immunoreactive neurons to electrical stimulation of hexamethonium-sensitive pathways. Putative sensory Dogiel type II calcitonin gene-related peptide-immunoreactive myenteric neurons may receive widespread fast synaptic inputs in mouse colon.

Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon

PubMed Central

Neunlist, Michel; Dobreva, Gisela; Schemann, Michael

1999-01-01

Using retrograde tracing with 1,1′-didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) in combination with electrophysiological and immunohistochemical techniques we determined the properties of the putative intrinsic primary afferent myenteric neurones with mucosal projections in the guinea-pig proximal colon. Eighty-four out of eighty-five DiI-labelled myenteric neurones were AH neurones with a late after-hyperpolarization. Thirty-three per cent of them exhibited atropine- and tetrodotoxin-resistant spontaneously occurring hyperpolarizing potentials (SHPs) during which the membrane resistance and excitability decreased. DiI-labelled AH neurones had multipolar Dogiel type II morphology, primarily of the dendritic type. Sixty-one per cent of the neurones were immunoreactive for choline acetyltransferase (ChAT) and calbindin (Calb) and 23% were ChAT positive but Calb negative. DiI-labelled neurones did not receive fast excitatory postsynaptic potentials but 94% (34/36) received slow excitatory postsynaptic potentials (sEPSPs). The neurokinin-3 (NK-3) agonist (MePhe7)-NKB but not the NK-1 agonist [(SAR9,Met(O2)11]-SP mimicked this response. The NK-3 receptor antagonist SR 142801 (1 μm) significantly decreased the amplitude and duration of the sEPSPs; the NK-1 receptor antagonist CP-99,994 (1 μm) was ineffective. Atropine (0.5 μm) increased the duration but not the amplitude of the sEPSPs. Microejection of 100 mM sodium butyrate onto the neurones induced in 90% of the DiI-labelled neurones a transient depolarization associated with an increased excitability. In neurones with SHPs sodium butyrate evoked, additionally, a late onset hyperpolarization. Perfusion of 0.1-10 mM sodium butyrate induced a dose-dependent increase in neuronal excitability. Sodium butyrate was ineffective when applied directly onto the mucosa. Mucosally projecting myenteric neurones of the colon are multipolar AH neurones with NK-3-mediated slow EPSPs and somal butyrate sensitivity. PMID:10332100

Anatomical study of prefixed versus postfixed brachial plexuses in adult human cadaver.

PubMed

Guday, Edengenet; Bekele, Asegedech; Muche, Abebe

2017-05-01

The brachial plexus is usually formed by the fusion of anterior primary rami of the fifth to eighth cervical and the first thoracic spinal nerves. Variations in the formation of the brachial plexus may occur. Variations in brachial plexus anatomy are important to radiologists, surgeons and anaesthesiologists performing surgical procedures in the neck, axilla and upper limb regions. These variations may lead to deviation from the expected dermatome distribution as well as differences in the motor innervation of muscles of the upper limb. This study is aimed to describe the anatomical variations of brachial plexus in its formation among 20 Ethiopian cadavers. Observational based study was conducted by using 20 cadavers obtained from the Department of Human Anatomy at University of Gondar, Bahir Dar, Addis Ababa, Hawasa, Hayat Medical College and St Paul Hospital Millennium Medical College. Data analysis was conducted using thematic approaches. A total of 20 cadavers examined bilaterally for the formation of brachial plexus. Of the 40 sides, 30 sides (75%) were found normal, seven sides (17.5%) prefixed, three sides (7.5%) postfixed and one side of the cadaver lacks cord formation. The brachial plexus formation in most subjects is found to be normal. Among the variants, the numbers of the prefixed brachial plexuses are greater than the postfixed brachial plexuses. © 2016 Royal Australasian College of Surgeons.

High resolution neurography of the lumbosacral plexus on 3T magneteic resonance imaging.

PubMed

Cejas, C; Escobar, I; Serra, M; Barroso, F

2015-01-01

Magnetic resonance neurography is a technique that complements clinical and electrophysiological study of the peripheral nerves and brachial and lumbosacral plexuses. Numerous focal processes (inflammatory, traumatic, primary tumors, secondary tumors) and diffuse processes (diabetic polyneuropathy, chronic idiopathic demyelinating polyneuropathy due to amyloidosis or Charcot-Marie-Tooth disease) can involve the lumbosacral plexus. This article reviews the anatomy of the lumbosacral plexus, describes the technique for neurography of the plexus at our institution, and shows the diverse diseases that affect it. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

PubMed Central

Schreiber, Dominik; Marx, Lisa; Felix, Silke; Clasohm, Jasmin; Weyland, Maximilian; Schäfer, Maximilian; Klotz, Markus; Lilischkis, Rainer; Erkel, Gerhard; Schäfer, Karl-Herbert

2017-01-01

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD. PMID:28824460

Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia.

PubMed

Rodriguez, Rodolfo; Ventura-Martinez, Rosa; Santiago-Mejia, Jacinto; Avila-Costa, Maria R; Fortoul, Teresa I

2006-02-01

1. We evaluated changes in contractility of the guinea-pig isolated ileum, using intact segments and myenteric plexus-longitudinal muscle (MPLM) preparations, after several times (5-160 min) of ischemia in situ. 2. Intestinal ischemia was produced by clamping the superior mesenteric artery. Ischemic and nonischemic segments, obtained from the same guinea-pig, were mounted in organ baths containing Krebs-bicarbonate (K-B) solution, maintained at 37 degrees C and gassed with 95% O2/5% CO2. The preparations were allowed to equilibrate for 60 min under continuous superfusion of warm K-B solution and then electrically stimulated at 40 V (0.3 Hz, 3.0 ms). Thereafter, complete noncumulative concentration-response curves were constructed for acetylcholine (ACh), histamine (HIS), potassium chloride (KCl), and barium chloride (BaCl2). Mean Emax (maximal response) values were calculated for each drug. 3. Our study shows that alterations of chemically and electrically evoked contractions are dependent on ischemic periods. It also demonstrates that contractile responses of ischemic tissues to neurogenic stimulation decreases earlier and to a significantly greater extent than the non-nerve mediated responses of the intestinal smooth muscle. Contractile responses to smooth muscle stimulants were all similarly affected by ischemia. Electron microscopy images indicated necrotic neuronal death. The decrease in reactivity of ischemic tissues to electrical stimulation was ameliorated by dexrazoxane, an antioxidant agent. 4. We consider the guinea-pig isolated ileum as a useful model system to study the processes involved in neuronal ischemia, and we propose that the reduction in maximal responses to electrical stimulation is a useful parameter to study neuroprotection.

Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model

PubMed Central

Corbett, A D; Lees, G M

1996-01-01

Since intermittent ischaemia may play an important role in the ætiology of Inflammatory Bowel Disease, particularly Crohn's Disease, a pharmacological model of neuronal ischaemia was applied to guinea-pig isolated intestinal preparations to mimic the acute effects of reduced blood flow on intestinal motility.Neuro-effector transmission and smooth muscle performance were examined in myenteric plexus-longitudinal muscle preparations of guinea-pig ileum exposed to sodium cyanide (NaCN), in order to inhibit oxidative phosphorylation, or to iodoacetic acid (IAA), to block glycolysis. Comparisons were made with the effects due to simple deprivation of oxygen or glucose.Depressions of cholinergic neuro-effector transmission induced by hypoxia or NaCN (effective concentration range 0.1–3 mM), given as separate treatments, singly or repetitively over 60–90 min, were apparent within 30 s and were reversible. The maximum inhibition was 90% and the IC50 for NaCN was 0.3 mM. A conspicuous component of these inhibitions was prejunctional.Non-cholinergic neuro-effector contractions were inhibited by up to 90% by anoxia or NaCN but recovery was incomplete and slower than with cholinergic contractions.Glucose-free solutions also caused a reversible failure of cholinergic neuro-effector transmission but of slower onset. In contrast, IAA (0.06–1 mM) abolished contractions irreversibly, apparently by a direct depressant effect on smooth muscle contraction. Unlike NaCN, IAA caused an initial potentiation of electrically-induced contractions, partly by a prejunctional potentiation of cholinergic neuro-effector transmission.It is concluded that a disruption of intestinal activity in pathological conditions associated with intestinal ischaemia may result from disturbances in the function of enteric neurones. PMID:9117084

HIRSCHSPRUNG'S DISEASE—The Clinical Differentiation and Treatment of Children with Hirschsprung's Disease and Pseudo-Hirschsprung's Disease

PubMed Central

Ravitch, Mark M.

1958-01-01

Hirschsprung's disease is marked by constipation from the time of birth, with the development, if uncorrected, of a protuberant abdomen and flared costal margins. The rectal ampulla is empty and the abdomen is filled with fecal masses. Pain is not prominent. Flatus is passed in large amounts. Encopresis does not occur. Barium enema shows the characteristic narrowed distal rectal segment and biopsy of the rectum shows absence of the ganglion cells of the myenteric plexus. Treatment is operative resection of the distal narrow segment and a primary anastomosis. Hirschsprung's disease may be mimicked in children with: 1. Psychogenic constipation—pseudo-Hirschsprung's disease. Unlike Hirschsprung's disease, symptoms do not appear at birth, encopresis is common, and the barium enema shows no narrow distal segment. 2. Mental retardation and cerebral defect. 3. Corrected imperforate anus—on the basis of stenosis, imperfect innervation or poor habit training. 4. Cretinism—with severe constipation and intestinal dilatation perhaps the presenting symptoms. Treatment of these four groups of children with severe constipation not due to Hirschsprung's disease is: For Group 1, open discussion with parent and child. Assumption by the physician of full control of the details of treatment, and relegation of parent to the role of the physician's agent in following the prescribed regimen. For Group 2, an enema regimen. Whereas fairly rapid restoration (and then persistence) of normal bowel habit can be expected in Group 1, the basic defects in Group 2 may require indefinite continuation of treatment. For Group 3, regular enema regimen, in the less severe cases—one identical with that used in Group 1, and dilatation of strictures or anoplasty. In Group 4, thyroid hormone therapy relieves the constipation of hypothyroidism and causes reversion of radiographic changes in the colon and rectum. PMID:13561108

Molecular Cloning of Ghrelin and Characteristics of Ghrelin-Producing Cells in the Gastrointestinal Tract of the Common Marmoset (Callithrix jacchus).

PubMed

Takemi, Shota; Sakata, Ichiro; Apu, Auvijit Saha; Tsukahara, Shinji; Yahashi, Satowa; Katsuura, Goro; Iwashige, Fumihiro; Akune, Atsushi; Inui, Akio; Sakai, Takafumi

2016-10-01

Ghrelin was first isolated from human and rat as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In the present study, we determined the ghrelin cDNA sequence of the common marmoset (Callithrix jacchus), a small-bodied New World monkey, and investigated the distribution of ghrelin-producing cells in the gastrointestinal tract and localization profiles with somatostatin-producing cells. The marmoset ghrelin cDNA coding region was 354 base pairs, and showed high homology to that in human, rhesus monkey, and mouse. Marmoset ghrelin consists of 28 amino acids, and the N-terminal region is highly conserved as found in other mammalian species. Marmoset preproghrelin and mature ghrelin have 86.3% and 92.9% homology, respectively, to their human counterparts. Quantitative RT-PCR analysis showed that marmoset ghrelin mRNA is highly expressed in the stomach, but it is not detected in other tissues of the gastrointestinal tract. In addition, a large number of ghrelin mRNA-expressing cells and ghrelin-immunopositive cells were detected in the mucosal layer of the stomach, but not in the myenteric plexus. Moreover, all the ghrelin cells examined in the stomach were observed to be closed-type. Double staining showed that somatostatin-immunopositive cells were not co-localized with ghrelin-producing cells; however, a subset of somatostatin-immunopositive cells is directly adjacent to ghrelin-immunopositive cells. These findings suggest that the distribution of ghrelin cells in marmoset differs from that in rodents, and thus the marmoset may be a more useful model for the translational study of ghrelin in primates. In conclusion, we have clarified the expression and cell distribution of ghrelin in marmoset, which may represent a useful model in translational study.

Autonomic Evaluation of Patients With Gastroparesis and Neurostimulation: Comparisons of Direct/Systemic and Indirect/Cardiac Measures

PubMed Central

Stocker, Abigail; Abell, Thomas L.; Rashed, Hani; Kedar, Archana; Boatright, Ben; Chen, Jiande

2016-01-01

Background Disorders of nausea, vomiting, abdominal pain, and related problems often are manifestations of gastrointestinal, neuromuscular, and/or autonomic dysfunction. Many of these patients respond to neurostimulation, either gastric electrical stimulation or electroacupuncture. Both of these therapeutic techniques appear to influence the autonomic nervous system which can be evaluated directly by traditional testing and indirectly by heart rate variability. Methods We studied patients undergoing gastric neuromodulation by both systemic autonomic testing (39 patients, six males and 33 females, mean age 38 years) and systemic autonomic testing and heart rate variability (35 patients, seven males and 28 females, mean age 37 years) testing before and after gastric neuromodulation. We also performed a pilot study using both systemic autonomic testing and heart rate variability in a small number of patients (five patients, all females, mean age 48.6 years) with diabetic gastroparesis at baseline to compare the two techniques at baseline. Systemic autonomic testing and heart rate variability were performed with standardized techniques and gastric electrical stimulation was performed as previously described with electrodes implanted serosally in the myenteric plexus. Results Both systemic autonomic testing and heart rate variability measures were often abnormal at baseline and showed changes after gastric neuromodulation therapy in two groups of symptomatic patients. Pilot data on a small group of similar patients with systemic automatic nervous measures and heart rate variability showed good concordance between the two techniques. Conclusions Both traditional direct autonomic measures and indirect measures such as heart rate variability were evaluated, including a pilot study of both methods in the same patient group. Both appear to be useful in evaluation of patients at baseline and after stimulation therapies; however, a future full head-to-head comparison is warranted. PMID:27785318

Colonic wall changes in patients with diverticular disease - is there a predisposition for a complicated course?

PubMed

Ulmer, T F; Rosch, R; Mossdorf, A; Alizai, H; Binnebösel, M; Neumann, U

2014-01-01

The aim of this study was to evaluate colonic wall changes and enteric neuropathy in patients with either uncomplicated (UDD) or complicated diverticular disease (CDD). Furthermore, we evaluated the presence of an anatomic sphincter at the rectosigmoid junction (RSJ). Samples of colonic tissue from fifteen patients with UDD, fifteen patients with CDD and fifteen patients as control were collected. Collagen quotient I/III was measured with the Sirius-red test, expression of MMP-1, MMP-13, innervation (S100), proliferation (Ki67) and apoptosis (TUNEL) in the colonic wall were investigated by immunohistochemical studies. Furthermore, measurements of the different layers were performed to investigate the RSJ. Patients with either UDD or CDD had lower collagen I/III quotients compared to the control group, significant for CDD (p = 0.007). For MMP-1 and MMP-13 only a slight increase for patients with CDD was found. The percentage of proliferating (Ki67) and apoptotic (TUNEL) cells was significantly higher for patients with CDD than in the control group (p = 0.016; p = 0.037). Upon investigating the S100-expression a significant reduce in glial cells density was found in the myenteric and mucosal plexus for both groups (UDD and CDD) compared to the control group. Measurements of the different colon layers oral, aboral and at the RSJ revealed equal values. This study has shown that colonic wall changes and enteric neuropathy seem to play a role in the pathogenesis of colonic diverticulosis. None of our results suggest a predisposition for a complicated diverticular disease. Furthermore, the presence of an anatomic sphincter at the rectosigmoid junction could not be detected. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Investigations of nerve populations influencing ion transport that can be stimulated electrically, by serotonin and by a nicotinic agonist.

PubMed

Keast, J R; Furness, J B; Costa, M

1985-11-01

It is known that the majority of the mucosal nerve fibres in the guinea-pig small intestine arise from submucous ganglia. There are a number of neurochemically distinct populations of nerve cells in these ganglia, approximately half of them being cholinergic. In these studies we have stimulated isolated preparations of mucosa and submucosa with electrical field stimulation (EFS), 5-hydroxytryptamine (5-HT) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and monitored changes in ion transport. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net ion transport across the tissue. EFS consisted of passing bipolar rectangular stimulus pulses through two platinum wires, one placed on each of the mucosal and submucosal sides of the tissue. EFS, 5-HT and DMPP each caused a transient increase in Isc. Tetrodotoxin (TTX) abolished all of the EFS response and the majority of the response observed with 5-HT or DMPP, suggesting that the action of these stimuli on the mucosa is primarily nerve-mediated. The TTX-sensitive responses to 5-HT (greater than 5 X 10(-7) M) and DMPP consisted of two components, appearing with different latencies. The response to EFS also consisted of two components. Hyoscine abolished the first component of each of these responses and significantly reduced the amplitude of the second, by 40% (for EFS and 5-HT) and 84% (for DMPP). At lower 5-HT concentrations, only the later component was seen, and this was unaffected by hyoscine.(ABSTRACT TRUNCATED AT 250 WORDS)

Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti-inflammatory actions through α7 nicotinic acetylcholine receptor activation.

PubMed

Endo, M; Hori, M; Mihara, T; Ozaki, H; Oikawa, T; Odaguchi, H; Hanawa, T

2017-12-01

We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action. The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT 4 R) knockout mice. Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT 4 R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI. © 2017 John Wiley & Sons Ltd.

Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system.

PubMed

Becker, Laren; Nguyen, Linh; Gill, Jaspreet; Kulkarni, Subhash; Pasricha, Pankaj Jay; Habtezion, Aida

2018-05-01

The enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS. Longitudinal muscle and myenteric plexus from small intestine of young, mid-aged and old mice were dissected and prepared for whole mount immunostaining, flow cytometry, Luminex immunoassays, western blot analysis, enteric neural stem cell (ENSC) isolation or conditioned media. Bone marrow derived macrophages were prepared and polarised to classic (M1) or alternative (M2) activation states. Markers for macrophage phenotype were measured using quantitative RT-PCR. Ageing causes a shift in macrophage polarisation from anti-inflammatory 'M2' to proinflammatory 'M1' that is associated with a rise in cytokines and immune cells in the ENS. This phenotypic shift is associated with a neural response to inflammatory signals, increase in apoptosis and loss of enteric neurons and ENSCs, and delayed intestinal transit. An age-dependent decrease in expression of the transcription factor FoxO3, a known longevity gene, contributes to the loss of anti-inflammatory behaviour in macrophages of old mice, and FoxO3-deficient mice demonstrate signs of premature ageing of the ENS. A shift by macrophages towards a proinflammatory phenotype with ageing causes inflammation-mediated degeneration of the ENS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Characterization of a neurokinin B receptor site in rat brain using a highly selective radioligand.

PubMed

Laufer, R; Gilon, C; Chorev, M; Selinger, Z

1986-08-05

We have recently characterized a tachykinin receptor subtype (SP-N) whose preferred ligand is the mammalian neuropeptide, neurokinin B (Laufer, R., Wormser, U., Friedman, Z. Y., Gilon, C., Chorev, M., and Selinger, Z. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7444-7448). To investigate this novel tachykinin receptor, we have now prepared a radiolabeled peptide, N alpha-[( 125I]desamino-3-iodotyrosyl)-[Asp5,6, N-methyl-Phe8]substance P (5-11) heptapeptide (125I-BH-NH-Senktide), which selectively interacts with the SP-N receptor subtype. The binding of 125I-BH-NH-Senktide to rat cerebral cortex membranes was studied under conditions that minimized nonspecific binding. Unlike other tachykinin receptor probes, this radioligand is not degraded during the binding experiment. Binding of 125I-BH-NH-Senktide is reversible, saturable, and of high affinity (KD = 0.9 nM). The radioligand labels a single class of binding site (122 fmol binding sites/mg of protein), as indicated by a linear Scatchard plot and a Hill coefficient close to unity (nH = 1.05). The pharmacological specificity of this binding site corresponds to that of the neuronal SP-N receptor in guinea pig ileum myenteric plexus, which was determined by a functional bioassay. Among various rat brain regions, the highest binding was observed in the cerebral cortex, olfactory bulb, hypothalamus, and hippocampus. These results suggest the existence and specific distribution of a neurokinin B receptor site of the SP-N type in rat brain. 125I-BH-NH-Senktide is the first selective and potent probe for this receptor and is thus an important tool for further studies of its distribution, regulation, and functional role.

Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model.

PubMed

Quan, Xiaojing; Luo, Hesheng; Fan, Han; Tang, Qincai; Chen, Wei; Cui, Ning; Yu, Guang; Xia, Hong

2015-08-01

Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility.

Telocytes in Crohn's disease.

PubMed

Milia, Anna Franca; Ruffo, Martina; Manetti, Mirko; Rosa, Irene; Conte, Dalila; Fazi, Marilena; Messerini, Luca; Ibba-Manneschi, Lidia

2013-12-01

Crohn's disease (CD) is a relapsing chronic inflammatory disorder that may involve all the gastrointestinal tract with a prevalence of terminal ileum. Intestinal lesions have a characteristic discontinuous and segmental distribution and may affect all layers of the gut wall. Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including gastrointestinal tract of humans and mammals. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility. The aim of our study was to investigate the presence and distribution of TC in disease-affected and -unaffected ileal specimens from CD patients compared with controls. TC were identified by CD34/PDGFRα immunohistochemistry. In affected CD specimens TC disappeared, particularly where fibrosis and architectural derangement of the intestinal wall were observed. In the thickened muscularis mucosae and submucosa, few TC entrapped in the fibrotic extracellular matrix were found. A discontinuous network of TC was present around smooth muscle bundles, ganglia and enteric strands in the altered muscularis propria. At the myenteric plexus, the loss of TC network was paralleled by the loss of interstitial cells of Cajal network. In the unaffected CD specimens, TC were preserved in their distribution. Our results suggest that in CD the loss of TC might have important pathophysiological implications contributing to the architectural derangement of the intestinal wall and gut dysmotility. Further functional studies are necessary to better clarify the role of TC loss in CD pathophysiology. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla).

PubMed

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-02-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. © 2013 Anatomical Society.

A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis

PubMed Central

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Guiducci, Serena; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

2014-01-01

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of the skin and various internal organs. In SSc, telocytes, a peculiar type of stromal (interstitial) cells, display severe ultrastructural damages and are progressively lost from the clinically affected skin. The aim of the present work was to investigate the presence and distribution of telocytes in the internal organs of SSc patients. Archival paraffin-embedded samples of gastric wall, myocardium and lung from SSc patients and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were studied on tissue sections subjected to CD34 immunostaining. CD34/CD31 double immunofluorescence was performed to unequivocally differentiate telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Few telocytes entrapped in the fibrotic extracellular matrix were found in the muscularis mucosae and submucosa of SSc gastric wall. In the muscle layers and myenteric plexus, the network of telocytes was discontinuous or even completely absent around smooth muscle cells and ganglia. Telocytes were almost completely absent in fibrotic areas of SSc myocardium. In SSc fibrotic lung, few or no telocytes were observed in the thickened alveolar septa, around blood vessels and in the interstitial space surrounding terminal and respiratory bronchioles. In SSc, the loss of telocytes is not restricted to the skin, but it is a widespread process affecting multiple organs targeted by the fibrotic process. As telocytes are believed to be key players in the regulation of tissue/organ homoeostasis, our data suggest that telocyte loss might have important pathophysiological implications in SSc. PMID:24467430

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.

PubMed

Lu, Ping; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Tang, Qincai; Yu, Guang; Chen, Wei; Xia, Hong

2016-04-01

The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function. Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome. Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L-type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique. Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP. Increased serum SP level and up-regulated NK1R in colon may contribute to stress-induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla)

PubMed Central

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-01-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. PMID:24433383

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon

PubMed Central

Hockley, James RF; Reed, David E; Smith, Ewan St. John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0–80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies. PMID:28566000

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Ultrasound of the Brachial Plexus.

PubMed

Griffith, James F

2018-07-01

Examination of the brachial plexus with ultrasound is efficient because it allows many parts of the brachial plexus as well as the surrounding soft tissues to be assessed with high spatial resolution. The key to performing good ultrasound of the brachial plexus is being familiar with the anatomy and the common variants. That makes it possible to concentrate solely on the ultrasound appearances free of simultaneously wondering about the anatomy. Ultrasound of the brachial plexus is particularly good for assessing nerve sheath tumor, perineural fibrosis, metastases, some inflammatory neuropathies, neuralgic amyotrophy, and posttraumatic sequalae. It is limited in the assessment of thoracic outlet syndrome and in the acute/subacute trauma setting. This review addresses the anatomy, ultrasound technique, as well as pathology of the brachial plexus from the cervical foramina to the axilla. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High resolution neurography of the brachial plexus by 3 Tesla magnetic resonance imaging.

PubMed

Cejas, C; Rollán, C; Michelin, G; Nogués, M

2016-01-01

The study of the structures that make up the brachial plexus has benefited particularly from the high resolution images provided by 3T magnetic resonance scanners. The brachial plexus can have mononeuropathies or polyneuropathies. The mononeuropathies include traumatic injuries and trapping, such as occurs in thoracic outlet syndrome due to cervical ribs, prominent transverse apophyses, or tumors. The polyneuropathies include inflammatory processes, in particular chronic inflammatory demyelinating polyneuropathy, Parsonage-Turner syndrome, granulomatous diseases, and radiation neuropathy. Vascular processes affecting the brachial plexus include diabetic polyneuropathy and the vasculitides. This article reviews the anatomy of the brachial plexus and describes the technique for magnetic resonance neurography and the most common pathologic conditions that can affect the brachial plexus. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Clearance of amyloid-β peptide across the choroid plexus in Alzheimer's disease.

PubMed

Alvira-Botero, Ximena; Carro, Eva M

2010-12-01

Aging and several neurodegenerative diseases bring about changes in the anatomy and physiology of the choroid plexus. The identification of specific membrane receptors that bind and internalize extracellular ligands has revolutionized the traditional roles of this tissue. Amyloid beta peptide (Aβ), the major constituent of the amyloid core of senile plaques in patients with Alzheimer's disease (AD) is known to contribute to disease neuropathology and progression. Recent emphasis on comorbidity of AD and a deficient clearance of Aβ across the blood-brain barrier and blood-cerebrospinal fluid barrier have highlighted the importance of brain Aβ clearance in AD. The megalin receptor has also been implicated in the pathogenesis of AD. Faulty Aβ clearance from the brain across the choroid plexus epithelium by megalin appears to mediate focal Aβ accumulation in AD. Patients with AD have reduced levels of megalin at the choroid plexus, which in turn seem to increase brain levels of Aβ through a decreased efflux of brain Aβ. Therapies that increase megalin expression at the choroid plexus could potentially control accumulation of brain Aβ. This review covers in depth the anatomy and function of the choroid plexus, focusing on the brain barrier at the choroid plexus, as it actively participates in Aβ clearance. In addition, we describe the role of the choroid plexus in brain functions, aging and AD, as well as the role of megalin in the process of Aβ clearance. Finally, we present current data on the use of choroid plexus cells to repair the damaged brain.

Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

PubMed

Safaee, Michael; Oh, Michael C; Bloch, Orin; Sun, Matthew Z; Kaur, Gurvinder; Auguste, Kurtis I; Tihan, Tarik; Parsa, Andrew T

2013-03-01

Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

Alimentary tract innervation deficits and dysfunction in mice lacking GDNF family receptor alpha2.

PubMed

Rossi, Jari; Herzig, Karl-Heinz; Võikar, Vootele; Hiltunen, Païvi H; Segerstråle, Mikael; Airaksinen, Matti S

2003-09-01

Subsets of parasympathetic and enteric neurons require neurturin signaling via glial cell line-derived neurotrophic factor family receptor alpha2 (GFRalpha2) for development and target innervation. Why GFRalpha2-deficient (Gfra2-/-) mice grow poorly has remained unclear. Here, we analyzed several factors that could contribute to the growth retardation. Neurturin mRNA was localized in the gut circular muscle. GFRalpha2 protein was expressed in most substance P-containing myenteric neurons, in most intrapancreatic neurons, and in surrounding glial cells. In the Gfra2-/- mice, density of substance P-containing myenteric ganglion cells and nerve bundles in the myenteric ganglion cell layer was significantly reduced, and transit of test material through small intestine was 25% slower compared to wild-type mice. Importantly, the knockout mice had approximately 80% fewer intrapancreatic neurons, severely impaired cholinergic innervation of the exocrine but not the endocrine pancreas, and increased fecal fat content. Vagally mediated stimulation of pancreatic secretion by 2-deoxy-glucose in vivo was virtually abolished. Retarded growth of the Gfra2-/- mice was accompanied by reduced fat mass and elevated basal metabolic rate. Moreover, the knockout mice drank more water than wild-type controls, and wet-mash feeding resulted in partial growth rescue. Taken together, the results suggest that the growth retardation in mice lacking GFRalpha2 is largely due to impaired salivary and pancreatic secretion and intestinal dysmotility.

Effects of early nerve repair on experimental brachial plexus injury in neonatal rats.

PubMed

Bourke, Gráinne; McGrath, Aleksandra M; Wiberg, Mikael; Novikov, Lev N

2018-03-01

Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

Real-time mapping of the corneal sub-basal nerve plexus by in vivo laser scanning confocal microscopy

NASA Astrophysics Data System (ADS)

Guthoff, Rudolf F.; Zhivov, Andrey; Stachs, Oliver

2010-02-01

The aim of the study was to produce two-dimensional reconstruction maps of the living corneal sub-basal nerve plexus by in vivo laser scanning confocal microscopy in real time. CLSM source data (frame rate 30Hz, 384x384 pixel) were used to create large-scale maps of the scanned area by selecting the Automatic Real Time (ART) composite mode. The mapping algorithm is based on an affine transformation. Microscopy of the sub-basal nerve plexus was performed on normal and LASIK eyes as well as on rabbit eyes. Real-time mapping of the sub-basal nerve plexus was performed in large-scale up to a size of 3.2mm x 3.2mm. The developed method enables a real-time in vivo mapping of the sub-basal nerve plexus which is stringently necessary for statistically firmed conclusions about morphometric plexus alterations.

Psammoma bodies - friends or foes of the aging choroid plexus.

PubMed

Jovanović, Ivan; Ugrenović, Sladjana; Vasović, Ljiljana; Petrović, Dragan; Cekić, Sonja

2010-06-01

Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma bodies formation in both tumors and choroid plexus and, that they might have harmful effect on choroid plexus structure and function during the aging process. Significantly higher degree of choroidal epithelial cells atrophy, in cases with present psammoma bodies proves that partially. Further researches should be focused on detection of osteopontin and nanobacteria, already detected in tumors psammoma bodies, in choroid plexus ones. Discovery of choroidal psammoma bodies mechanisms formation can be important for elucidation of some aspects in pathogenesis of some tumors, too. Application of choroid plexus epithelial cells functional markers in cases with psammoma bodies should show their functional status.

The choroid plexus: a comprehensive review of its history, anatomy, function, histology, embryology, and surgical considerations.

PubMed

Mortazavi, Martin M; Griessenauer, Christoph J; Adeeb, Nimer; Deep, Aman; Bavarsad Shahripour, Reza; Shahripour, Reza Bavarsad; Loukas, Marios; Tubbs, Richard Isaiah; Tubbs, R Shane

2014-02-01

The role of the choroid plexus in cerebrospinal fluid production has been identified for more than a century. Over the years, more intensive studies of this structure has lead to a better understanding of the functions, including brain immunity, protection, absorption, and many others. Here, we review the macro- and microanatomical structure of the choroid plexus in addition to its function and embryology. The literature was searched for articles and textbooks for data related to the history, anatomy, physiology, histology, embryology, potential functions, and surgical implications of the choroid plexus. All were gathered and summarized comprehensively. We summarize the literature regarding the choroid plexus and its surgical implications.

Primary benign brachial plexus tumors: an experience of 115 operated cases.

PubMed

Desai, Ketan I

2012-01-01

Primary benign brachial plexus tumors are rare. They pose a great challenge to the neurosurgeon, because the majority of patients present with minimal or no neurological deficits. Radical to complete excision of the tumor with preservation of neurological function of the involved nerve is an ideal surgical treatment option with benign primary brachial plexus tumor surgery. We present a review article of our 10-year experience with primary benign brachial plexus tumors surgically treated at King Edward Memorial Hospital and P.D. Hinduja National Hospital from 2000 to 2009. The clinical presentations, radiological features, surgical strategies, and the eventual outcome following surgery are analyzed, discussed, and compared with available series in the world literature. Various difficulties and problems faced in the management of primary benign brachial plexus tumors are analyzed. Irrespective of the tumor size, the indications for surgical intervention are also discussed. The goal of our study was to optimize the treatment of patients with benign brachial plexus tumors with minimal neurological deficits. It is of paramount importance that brachial plexus tumors be managed by a peripheral nerve surgeon with expertise and experience in this field to minimize the neurological insult following surgery.

Risk factors for clavicle fracture concurrent with brachial plexus injury.

PubMed

Karahanoglu, Ertugrul; Kasapoglu, Taner; Ozdemirci, Safak; Fadıloglu, Erdem; Akyol, Aysegul; Demirdag, Erhan; Yalvac, E Serdar; Kandemir, N Omer

2016-04-01

The aim of this study was to evaluate the risk factors for clavicle fracture concurrent with brachial plexus injuries. A retrospective study was conducted at a tertiary centre. The hospital records of 62,288 vaginal deliveries were evaluated retrospectively. There were 35 cases of brachial plexus injury. Of these patients, nine had brachial plexus injuries with clavicle fracture and 26 without clavicle fracture. The analysed risk factors for clavicle fracture concurrent with brachial plexus injury were gestational diabetes, labour induction and augmentation, prolonged second stage of labour, estimated foetal weight above 4000 g, birth weight above 4000 g, risky working hours, and the requirement of manoeuvres to free the impacted shoulder from behind the symphysis pubis. Labour augmentation with oxytocin increased the risk of clavicle fracture in cases of brachial plexus injury (OR 6.67; 95% CI 1.26-35.03). A birth weight higher than 4000 g also increased the risk of clavicle fracture. Risky working hours, gestational diabetes, estimated foetal weight higher than 4000 g, and requirement of shoulder dystocia manoeuvres did not increase the risk of clavicle fracture. Labour augmentation and actual birth weight higher than 4000 g were identified as risk factors for clavicle fracture in cases of brachial plexus injury.

Choroid plexus papilloma in a beluga whale (Delphinapterus leucas).

PubMed

Thomas, Christian; Mergl, June; Gehring, Erica; Paulus, Werner; Martineau, Daniel; Hasselblatt, Martin

2016-07-01

We report herein a choroid plexus papilloma in a beluga whale (Delphinapterus leucas). This case was positive for choroid plexus tumor marker Kir7.1 on immunohistochemistry. These results and the high conservation of Kir7.1 across species at the amino acid sequence level strongly suggest that antibodies directed against Kir7.1 not only can be employed for the diagnosis of choroid plexus tumors in cetaceans, but are also likely to be diagnostically useful in other animal species. © 2016 The Author(s).

Hand Sensorimotor Function in Older Children With Neonatal Brachial Plexus Palsy.

PubMed

Brown, Susan H; Wernimont, Cory W; Phillips, Lauren; Kern, Kathy L; Nelson, Virginia S; Yang, Lynda J-S

2016-03-01

Routine sensory assessments in neonatal brachial plexus palsy are infrequently performed because it is generally assumed that sensory recovery exceeds motor recovery. However, studies examining sensory function in neonatal brachial plexus palsy have produced equivocal findings. The purpose of this study was to examine hand sensorimotor function in older children with neonatal brachial plexus palsy using standard clinical and research-based measures of tactile sensibility. Seventeen children with neonatal brachial plexus palsy (mean age: 11.6 years) and 19 age-matched controls participated in the study. Functional assessments included grip force, monofilament testing, and hand dexterity (Nine-Hole Peg, Jebsen-Taylor Hand Function). Tactile spatial perception involving the discrimination of pin patterns and movement-enhanced object recognition (stereognosis) were also assessed. In the neonatal brachial plexus palsy group, significant deficits in the affected hand motor function were observed compared with the unaffected hand. Median monofilament scores were considered normal for both hands. In contrast, tactile spatial perception was impaired in the neonatal brachial plexus palsy group. This impairment was seen as deficits in both pin pattern and object recognition accuracy as well as the amount of time required to identify patterns and objects. Tactile pattern discrimination time significantly correlated with performance on both functional assessment tests (P < 0.01). This study provides evidence that tactile perception deficits may accompany motor deficits in neonatal brachial plexus palsy even when measures of tactile registration (i.e., monofilament testing) are normal. These results may reflect impaired processing of somatosensory feedback associated with reductions in goal-directed upper limb use and illustrate the importance of including a broader range of sensory assessments in neonatal brachial plexus palsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: amchen@mednet.ucla.edu; Wang, Pin-Chieh; Daly, Megan E.

2014-03-15

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%)more » underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.« less

Expression of regulatory proteins in choroid plexus changes in early stages of Alzheimer disease.

PubMed

Krzyzanowska, Agnieszka; García-Consuegra, Inés; Pascual, Consuelo; Antequera, Desiree; Ferrer, Isidro; Carro, Eva

2015-04-01

Recent studies indicate that the choroid plexus has important physiologic and pathologic roles in Alzheimer disease (AD). To obtain additional insight on choroid plexus function, we performed a proteomic analysis of choroid plexus samples from patients with AD stages I to II (n = 16), III to IV (n = 16), and V to VI (n = 11) and 7 age-matched control subjects. We used 2-dimensional differential gel electrophoresis coupled with mass spectrometry to generate a complete picture of changes in choroid plexus protein expression occurring in AD patients. We identified 6 proteins: 14-3-3 β/α, 14-3-3 ε, moesin, proteasome activator complex subunit 1, annexin V, and aldehyde dehydrogenase, which were significantly regulated in AD patient samples (p < 0.05, >1.5-fold variation in expression vs control samples). These proteins are implicated in major physiologic functions including mitochondrial dysfunction and apoptosis regulation. These findings contribute additional significance to the emerging importance of molecular and functional changes of choroid plexus function in the pathophysiology of AD.

Concepts of nerve regeneration and repair applied to brachial plexus reconstruction.

PubMed

Bertelli, Jayme Augusto; Ghizoni, Marcos Flávio

2006-01-01

Brachial plexus injury is a serious condition that usually affects young adults. Progress in brachial plexus repair is intimately related to peripheral nerve surgery, and depends on clinical and experimental studies. We review the rat brachial plexus as an experimental model, together with its behavioral evaluation. Techniques to repair nerves, such as neurolysis, nerve coaptation, nerve grafting, nerve transfer, fascicular transfer, direct muscle neurotization, and end-to-side neurorraphy, are discussed in light of the authors' experimental studies. Intradural repair of the brachial plexus by graft implants into the spinal cord and motor rootlet transfer offer new possibilities in brachial plexus reconstruction. The clinical experience of intradural repair is presented. Surgical planning in root rupture or avulsion is proposed. In total avulsion, the authors are in favor of the reconstruction of thoraco-brachial and abdomino-antebrachial grasping, and on the transfer of the brachialis muscle to the wrist extensors if it is reinnervated. Surgical treatment of painful conditions and new drugs are also discussed.

[Choroid plexus tumours in childhood: Experience in Sant Joan de Déu hospital].

PubMed

Del Río-Pérez, Clara Maria; Suñol-Capella, Mariona; Cruz-Martinez, Ofelia; Garcia-Fructuoso, Gemma

2016-01-01

Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Anatomy of the nerves and ganglia of the aortic plexus in males

PubMed Central

Beveridge, Tyler S; Johnson, Marjorie; Power, Adam; Power, Nicholas E; Allman, Brian L

2015-01-01

It is well accepted that the aortic plexus is a network of pre- and post-ganglionic nerves overlying the abdominal aorta, which is primarily involved with the sympathetic innervation to the mesenteric, pelvic and urogenital organs. Because a comprehensive anatomical description of the aortic plexus and its connections with adjacent plexuses are lacking, these delicate structures are prone to unintended damage during abdominal surgeries. Through dissection of fresh, frozen human cadavers (n = 7), the present study aimed to provide the first complete mapping of the nerves and ganglia of the aortic plexus in males. Using standard histochemical procedures, ganglia of the aortic plexus were verified through microscopic analysis using haematoxylin & eosin (H&E) and anti-tyrosine hydroxylase stains. All specimens exhibited four distinct sympathetic ganglia within the aortic plexus: the right and left spermatic ganglia, the inferior mesenteric ganglion and one previously unidentified ganglion, which has been named the prehypogastric ganglion by the authors. The spermatic ganglia were consistently supplied by the L1 lumbar splanchnic nerves and the inferior mesenteric ganglion and the newly characterized prehypogastric ganglion were supplied by the left and right L2 lumbar splanchnic nerves, respectively. Additionally, our examination revealed the aortic plexus does have potential for variation, primarily in the possibility of exhibiting accessory splanchnic nerves. Clinically, our results could have significant implications for preserving fertility in men as well as sympathetic function to the hindgut and pelvis during retroperitoneal surgeries. PMID:25382240

The p75 neurotrophin receptor localization in blood-CSF barrier: expression in choroid plexus epithelium.

PubMed

Spuch, Carlos; Carro, Eva

2011-05-11

The presence of neurotrophins and their receptors Trk family has been reported in the choroid plexus. High levels of Nerve Growth Factor (NGF), Neurotrophin-4 (NT-4) and TrkB receptor were detected, while nothing was know about p75 neurotrophin receptor (p75NTR) in the choroid plexus epithelial cells. In neurons, p75NTR receptor has a dual function: promoting survival together with TrkA in response to NGF, and inducing apoptotic signaling through p75NTR. We postulated that p75NTR may also affect the survival pathways in the choroid plexus and also undergoes regulated proteolysis with metalloproteases. Here, we demonstrated the presence of p75NTR receptor in the choroid plexus epithelial cells. The p75NTR receptor would be involved in cell death mechanisms and in the damaged induced by amyloid beta (Aβ) in the choroid plexus and finally, we propose an essential role of p75NTR in the Aβ transcytosis through out choroid plexus barrier. The presence analysis reveals the new localization of p75NTR in the choroid plexus and, the distribution mainly in the cytoplasm and cerebrospinal fluid (CSF) side of the epithelial cells. We propose that p75NTR receptor plays a role in the survival pathways and Aβ-induced cell death. These data suggest that p75NTR dysfunction play an important role in the pathogenesis of brain diseases. The importance and novelty of this expression expands a new role of p75NTR.

Correlation between ultrasound imaging, cross-sectional anatomy, and histology of the brachial plexus: a review.

PubMed

van Geffen, Geert J; Moayeri, Nizar; Bruhn, Jörgen; Scheffer, Gert J; Chan, Vincent W; Groen, Gerbrand J

2009-01-01

The anatomy of the brachial plexus is complex. To facilitate the understanding of the ultrasound appearance of the brachial plexus, we present a review of important anatomic considerations. A detailed correlation of reconstructed, cross-sectional gross anatomy and histology with ultrasound sonoanatomy is provided.

Types and severity of operated supraclavicular brachial plexus injuries caused by traffic accidents.

PubMed

Kaiser, Radek; Waldauf, Petr; Haninec, Pavel

2012-07-01

Brachial plexus injuries occur in up to 5% of polytrauma cases involving motorcycle accidents and in approximately 4% of severe winter sports injuries. One of the criteria for a successful operative therapy is the type of lesion. Upper plexus palsy has the best prognosis, whereas lower plexus palsy is surgically untreatable. The aim of this study was to evaluate a group of patients with brachial plexus injury caused by traffic accidents, categorize the injuries according to type of accident, and look for correlations between type of palsy (injury) and specific accidents. A total of 441 brachial plexus reconstruction patients from our department were evaluated retrospectively(1993 to 2011). Sex, age, neurological status, and the type and cause of injury were recorded for each case. Patients with BPI caused by a traffic accident were assessed in detail. Traffic accidents were the cause of brachial plexus injury in most cases (80.7%). The most common type of injury was avulsion of upper root(s) (45.7%) followed by rupture (28.2%), complete avulsion (16.9%) and avulsion of lower root(s) (9.2%). Of the patients, 73.9% had an upper,22.7% had a complete and only 3.4% had a lower brachial plexus palsy. The main cause was motorcycle accidents(63.2%) followed by car accidents (23.5%), bicycle accidents(10.7%) and pedestrian collisions (3.1%) (p<0.001).Patients involved in car accidents had a higher percentage of lower avulsion (22.7%) and a lower percentage of upper avulsion (29.3%), whereas cyclists had a higher percentage of upper avulsion (68.6%) based on the data from the entire group of patients (p<0.001). Lower plexus palsy was significantly increased in patients after car accidents (9.3%,p<0.05). In the two main groups (car and motorcycle accidents),significantly more upper and fewer lower palsies were present. In the bicycle accident group, upper palsy was the most common (89%). Study results indicate that the most common injury was an upper plexus palsy. It was characteristic of bicycle accidents, and significantly more common in car and motorcycle accidents. The results also indicate that it is important to consider the potential of a brachial plexus injury after serious traffic accidents and to examine both upper extremities in detail even if some motor function is preserved.

Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity

PubMed Central

2013-01-01

Background The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Results Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood–brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Conclusions Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes. PMID:23497014

Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity.

PubMed

Bowyer, John F; Patterson, Tucker A; Saini, Upasana T; Hanig, Joseph P; Thomas, Monzy; Camacho, Luísa; George, Nysia I; Chen, James J

2013-03-05

The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood-brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes.

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

PubMed Central

Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS. PMID:19032979

Topsy-turvy: Turning the counter-current heat exchange of leatherback turtles upside down

USGS Publications Warehouse

Davenport, John; Jones, T. Todd; Work, Thierry M.; Balazs, George H.

2015-01-01

Counter-current heat exchangers associated with appendages of endotherms feature bundles of closely applied arteriovenous vessels. The accepted paradigm is that heat from warm arterial blood travelling into the appendage crosses into cool venous blood returning to the body. High core temperature is maintained, but the appendage functions at low temperature. Leatherback turtles have elevated core temperatures in cold seawater and arteriovenous plexuses at the roots of all four limbs. We demonstrate that plexuses of the hindlimbs are situated wholly within the hip musculature, and that, at the distal ends of the plexuses, most blood vessels supply or drain the hip muscles, with little distal vascular supply to, or drainage from the limb blades. Venous blood entering a plexus will therefore be drained from active locomotory muscles that are overlaid by thick blubber when the adults are foraging in cold temperate waters. Plexuses maintain high limb muscle temperature and avoid excessive loss of heat to the core, the reverse of the accepted paradigm. Plexuses protect the core from overheating generated by muscular thermogenesis during nesting.

Topsy-turvy: turning the counter-current heat exchange of leatherback turtles upside down.

PubMed

Davenport, John; Jones, T Todd; Work, Thierry M; Balazs, George H

2015-10-01

Counter-current heat exchangers associated with appendages of endotherms feature bundles of closely applied arteriovenous vessels. The accepted paradigm is that heat from warm arterial blood travelling into the appendage crosses into cool venous blood returning to the body. High core temperature is maintained, but the appendage functions at low temperature. Leatherback turtles have elevated core temperatures in cold seawater and arteriovenous plexuses at the roots of all four limbs. We demonstrate that plexuses of the hindlimbs are situated wholly within the hip musculature, and that, at the distal ends of the plexuses, most blood vessels supply or drain the hip muscles, with little distal vascular supply to, or drainage from the limb blades. Venous blood entering a plexus will therefore be drained from active locomotory muscles that are overlaid by thick blubber when the adults are foraging in cold temperate waters. Plexuses maintain high limb muscle temperature and avoid excessive loss of heat to the core, the reverse of the accepted paradigm. Plexuses protect the core from overheating generated by muscular thermogenesis during nesting. © 2015 The Author(s).

The prognostic value of concurrent phrenic nerve palsy in newborn babies with neonatal brachial plexus palsy.

PubMed

Yoshida, Kiyoshi; Kawabata, Hidehiko

2015-06-01

To investigate the prognostic value of concurrent phrenic nerve palsy for predicting spontaneous motor recovery in neonatal brachial plexus palsy. We reviewed the records of 366 neonates with brachial plexus palsy. The clinical and follow-up data of patients with and without phrenic nerve palsy were compared. Of 366 newborn babies with neonatal brachial plexus palsy, 21 (6%) had concurrent phrenic nerve palsy. Sixteen of these neonates had upper-type palsy and 5 had total-type palsy. Poor spontaneous motor recovery was observed in 13 neonates with concurrent phrenic nerve palsy (62%) and in 129 without concurrent phrenic nerve palsy (39%). Among neonates born via vertex delivery, poor motor recovery was observed in 7 of 9 (78%) neonates with concurrent phrenic nerve palsy and 115 of 296 (39%) without concurrent phrenic nerve palsy. Concurrent phrenic nerve palsy in neonates with brachial plexus palsy has prognostic value in predicting poor spontaneous motor recovery of the brachial plexus, particularly after vertex delivery. Therapeutic IV. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Avulsion of the brachial plexus in a great horned owl (Bubo virginaus)

USGS Publications Warehouse

Moore, M.P.; Stauber, E.; Thomas, N.J.

1989-01-01

Avulsion of the brachial plexus was documented in a Great Horned Owl (Bubo virginianus). A fractured scapula was also present. Cause of these injuries was not known but was thought to be due to trauma. Differentiation of musculoskeletal injury from peripheral nerve damage can be difficult in raptors. Use of electromyography and motor nerve conduction velocity was helpful in demonstrating peripheral nerve involvement. A brachial plexus avulsion was suspected on the basis of clinical signs, presence of electromyographic abnormalities in all muscles supplied by the nerves of the brachial plexus and absence of median-ulnar motor nerve conduction velocities.

Management of birth brachial plexus palsy.

PubMed

O'Brien, Donncha F; Park, T S; Noetzel, Michael J; Weatherly, Trisha

2006-02-01

The indications for surgical repair of congenital brachial plexus palsy are controversial. Our objective was to determine the results of early brachial plexus surgery following obstetric-induced brachial plexus palsy. We performed a retrospective analysis of the outcome of 58 cases of brachial plexus surgery. The indication for operation consisted of the presence of less than antigravity strength in the biceps, triceps, and deltoid muscle groups at 6 months of age. Data gathered prospectively, previously, showed the likelihood of improvement with less than antigravity strength in these cases to be poor. Follow-up data were obtained on 52 of the 58 cases. Overall mean follow-up was 2 years. Twelve patients had more than 3 years follow-up (mean 5.5 years, range 3-11.5 years). Significant improvement was seen in all injury patterns i.e., C5-C6, C5-C7, and C5-C8, T1. Greater than antigravity strength in the biceps, triceps, and deltoid muscle groups was seen in the majority of cases at follow-up. Repair of obstetrical brachial plexus palsy in children at 6 months of age that is based on less than antigravity strength in the biceps, triceps, and deltoid muscle groups produces improvement in functional capabilities. Children with obstetrical brachial plexus palsy should be referred soon after birth to a center that specializes in the treatment of this type of palsy.

Prevalence of brachial plexus injuries in patients with scapular fractures: A National Trauma Data Bank review

PubMed Central

Chamata, Edward; Mahabir, Raman; Jupiter, Daniel; Weber, Robert A

2014-01-01

BACKGROUND: Studies investigating the prevalence of brachial plexus injuries associated with scapular fractures are sparse, and are frequently limited by small sample sizes and often restricted to single-centre experience. OBJECTIVE: To determine the prevalence of brachial plexus injuries associated with scapular fractures; to determine how the prevalence varies with the region of the scapula injured; and to assess which specific nerves of the brachial plexus were involved. METHODS: The present study was a retrospective review of data from the National Trauma Data Bank over a five-year period (2007 to 2011). RESULTS: Of 68,118 patients with scapular fractures, brachial plexus injury was present in 1173 (1.72%). In patients with multiple scapular fractures, the prevalence of brachial plexus injury was 3.12%, and ranged from 1.52% to 2.22% in patients with single scapular fractures depending on the specific anatomical location of the fracture. Of the 426 injuries with detailed information on nerve injury, 208 (49%) involved the radial nerve, 113 (26.5%) the ulnar nerve, 65 (15%) the median nerve, 36 (8.5%) the axillary nerve and four (1%) the musculocutaneous nerve. CONCLUSION: The prevalence of brachial plexus injuries in patients with scapular fractures was 1.72%. The prevalence was similar across anatomical regions for single scapular fracture and was higher with multiple fractures. The largest percentage of nerve injuries were to the radial nerve. PMID:25535462

Constraint-Induced Movement Therapy for Children with Obstetric Brachial Plexus Palsy: Two Single-Case Series

ERIC Educational Resources Information Center

Buesch, Francisca Eugster

2010-01-01

The objective of this pilot study was to investigate the feasibility of constraint-induced movement therapy (CIMT) in children with obstetric brachial plexus palsy and receive preliminary information about functional improvements. Two patients (age 12 years) with obstetric brachial plexus palsy were included for a 126-h home-based CIMT…

Frontal slab composite magnetic resonance neurography of the brachial plexus: implications for infraclavicular block approaches.

PubMed

Raphael, David T; McIntee, Diane; Tsuruda, Jay S; Colletti, Patrick; Tatevossian, Ray

2005-12-01

Magnetic resonance neurography (MRN) is an imaging method by which nerves can be selectively highlighted. Using commercial software, the authors explored a variety of approaches to develop a three-dimensional volume-rendered MRN image of the entire brachial plexus and used it to evaluate the accuracy of infraclavicular block approaches. With institutional review board approval, MRN of the brachial plexus was performed in 10 volunteer subjects. MRN imaging was performed on a GE 1.5-tesla magnetic resonance scanner (General Electric Healthcare Technologies, Waukesha, WI) using a phased array torso coil. Coronal STIR and T1 oblique sagittal sequences of the brachial plexus were obtained. Multiple software programs were explored for enhanced display and manipulation of the composite magnetic resonance images. The authors developed a frontal slab composite approach that allows single-frame reconstruction of a three-dimensional volume-rendered image of the entire brachial plexus. Automatic segmentation was supplemented by manual segmentation in nearly all cases. For each of three infraclavicular approaches (posteriorly directed needle below midclavicle, infracoracoid, or caudomedial to coracoid), the targeting error was measured as the distance from the MRN plexus midpoint to the approach-targeted site. Composite frontal slabs (coronal views), which are single-frame three-dimensional volume renderings from image-enhanced two-dimensional frontal view projections of the underlying coronal slices, were created. The targeting errors (mean +/- SD) for the approaches-midclavicle, infracoracoid, caudomedial to coracoid-were 0.43 +/- 0.67, 0.99 +/- 1.22, and 0.65 +/- 1.14 cm, respectively. Image-processed three-dimensional volume-rendered MNR scans, which allow visualization of the entire brachial plexus within a single composite image, have educational value in illustrating the complexity and individual variation of the plexus. Suggestions for improved guidance during infraclavicular block procedures are presented.

Thermoablation of Liver Metastases: Efficacy of Temporary Celiac Plexus Block

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beck, A.N., E-mail: alexander.beck@charite.de; Schaefer, M.; Werk, M.

Purpose. To determine the efficacy of celiac plexus block during thermoablation of liver metastases. Methods. Fifty-five consecutive patients underwent thermoablation therapy of liver tumors by laser-induced thermotherapy. Twenty-nine patients received a temporary celiac plexus block, 26 patients acted as control group. In both groups fentanyl and midazolam were administered intravenously upon request of the patient. The duration of the intervention, consumption of opiates, and individual pain sensations were documented. Results. No complications resulting from the celiac plexus block were recorded. Celiac plexus block significantly reduced the amount of pain medication used during thermoablation therapy of liver tumors (with block, 2.45more » {mu}g fentanyl per kg body weight; without block, 3.58 {mu}g fentanyl per kg body weight, p < 0.05; midazolam consumption was not reduced) in patients with metastases {<=}5 mm from the liver capsule. For metastases farther away from the capsule no significant differences in opiate consumption were seen. Celiac plexus block reduced the time for thermoablation significantly (178 min versus 147 min, p < 0.05) no matter how far the metastases were from the liver capsule. Average time needed to set the block was 12 min (range 9-15 min); additional costs for the block were marginal. As expected (as pain medications were given according to individual patients' needs) pain indices did not differ significantly between the two groups. Conclusion. In patients with liver metastases {<=}5 mm from the liver capsule, celiac plexus block reduces the amount of opiates necessary, simplifying patient monitoring. In addition celiac plexus block reduces intervention time, with positive effects on overall workflow for all patients.« less

Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

PubMed Central

Vargas, Teo; Antequera, Desiree; Ugalde, Cristina; Spuch, Carlos; Carro, Eva

2010-01-01

Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β (Aβ) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβ accumulation at the choroid plexus epithelium remain unclear. Aβ clearance, from the brain to the blood, involves Aβ carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD. PMID:20369065

Syringomyelia with intramedullary ectopic choroid plexus: Case report.

PubMed

Duan, Hongzhou; Zhang, Jiayong; Xu, Feifan; Zhang, Zongqiang; Zhao, Xiaowen

2018-06-01

Intramedullary ectopic choroid plexus is rarely reported, here, we reported a rare case of symptomatic syringomyelia resulted of intramedullary ectopic choroid plexus. The patient was a 30-year-old female who presented with a 2-month history of progressive pain of upper back and bilateral ankle joint and progressive loss of upper-extremity function. MRI examination showed an intramedullary cystic lesion at T2-T4 without enhancement. Operative exploration was indicated. A reddish vascular villus-like lesion was found being located in the left dorsal part of the cyst, which was enblock removed and was confirmed as an ectopic choroid plexus tissue by pathological examination. The patient recovered uneventful and the symptom resolved during follow-up. Although ectopic choroid plexus is extremely rare, it should be taken into acount in the differential diagnosis of pathogenesis in syringomyelia or intramedullary cyst, aggressive surgical exploration should be considered when necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

First bite syndrome: our experience of laser tympanic plexus ablation.

PubMed

Amin, N; Pelser, A; Weighill, J

2014-02-01

First bite syndrome is a condition characterised by severe facial pain brought on by the first bite of each meal. This can severely affect the patient's ability to eat. We present a 70-year-old woman for whom we performed a laser ablation of the left ear tympanic plexus, as treatment of first bite syndrome. A permeatal approach was used to raise a tympanomeatal flap. The tympanic plexus was identified on the promontory and a 4 mm2 area of the plexus was ablated using CO2 laser. The flap was repositioned and a dressing was placed with topical antibiotics. At two-month follow up, there was full resolution of the patient's symptoms. First bite syndrome carries a high morbidity; treatment options are variable, and often unsuccessful. We describe the first documented case of laser tympanic plexus ablation, with a very effective initial response. This procedure represents a useful therapeutic option for first bite syndrome.

Brachial Plexus Injuries in Adults: Evaluation and Diagnostic Approach

PubMed Central

Sakellariou, Vasileios I.; Badilas, Nikolaos K.; Mazis, George A.; Stavropoulos, Nikolaos A.; Kotoulas, Helias K.; Kyriakopoulos, Stamatios; Tagkalegkas, Ioannis; Sofianos, Ioannis P.

2014-01-01

The increased incidence of motor vehicle accidents during the past century has been associated with a significant increase in brachial plexus injuries. New imaging studies are currently available for the evaluation of brachial plexus injuries. Myelography, CT myelography, and magnetic resonance imaging (MRI) are indicated in the evaluation of brachial plexus. Moreover, a series of specialized electrodiagnostic and nerve conduction studies in association with the clinical findings during the neurologic examination can provide information regarding the location of the lesion, the severity of trauma, and expected clinical outcome. Improvements in diagnostic approaches and microsurgical techniques have dramatically changed the prognosis and functional outcome of these types of injuries. PMID:24967130

Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins.

PubMed

Rouault, Tracey A; Zhang, De-Liang; Jeong, Suh Young

2009-12-01

Maintenance of appropriate iron homeostasis in the brain is important, but the mechanisms involved in brain iron uptake are incompletely understood. Here, we have analyzed where messenger RNAs that encode iron transport proteins are expressed in the brain, using the Allen Brain atlas, and we conclude that several important iron transporters are highly expressed in the choroid plexus. Based on recent estimates of the surface area of the choroid plexus and on MRI imaging studies of manganese uptake in the brain, we propose that the choroid plexus may have a much greater role than has been previously appreciated in brain iron transport.

Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens.

PubMed Central

Chen, J D; Van Dyke, T

1991-01-01

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis. Images PMID:1658622

[Surgical treatment of children with brachial plexus paralysis].

PubMed

Grossman, J A; Ramos, L E; Tidwell, M; Price, A; Papazian, O; Alfonso, I

1998-08-01

A variety of surgical procedures exist for early repair of the nerve injury in obstetrical brachial plexus palsy, including neuroma excision and nerve grafting, neurolysis and neurotization. Secondary deformities of the shoulder, forearm, and hand can similarly be reconstructed using soft tissue and skeletal procedures. This review describes our surgical approach to maximize the ultimate functional outcome in infants and children with obstetrical brachial plexus palsy.

Pathological alteration in the choroid plexus of Alzheimer's disease: implication for new therapy approaches.

PubMed

Krzyzanowska, Agnieszka; Carro, Eva

2012-01-01

Morphological alterations of choroid plexus in Alzheimer's disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide. Here, we review new evidences for AD-related changes in the choroid plexus. The data suggest that the significantly altered functions of the choroid plexus contribute to the multiparametric pathogenesis of late-onset AD.

The natural history and management of brachial plexus birth palsy.

PubMed

Buterbaugh, Kristin L; Shah, Apurva S

2016-12-01

Brachial plexus birth palsy (BPBP) is an upper extremity paralysis that occurs due to traction injury of the brachial plexus during childbirth. Approximately 20 % of children with brachial plexus birth palsy will have residual neurologic deficits. These permanent and significant impacts on upper limb function continue to spur interest in optimizing the management of a problem with a highly variable natural history. BPBP is generally diagnosed on clinical examination and does not typically require cross-sectional imaging. Physical examination is also the best modality to determine candidates for microsurgical reconstruction of the brachial plexus. The key finding on physical examination that determines need for microsurgery is recovery of antigravity elbow flexion by 3-6 months of age. When indicated, both microsurgery and secondary shoulder and elbow procedures are effective and can substantially improve functional outcomes. These procedures include nerve transfers and nerve grafting in infants and secondary procedures in children, such as botulinum toxin injection, shoulder tendon transfers, and humeral derotational osteotomy.

The diagnostic accuracy of 1.5T magnetic resonance imaging for detecting root avulsions in traumatic adult brachial plexus injuries.

PubMed

Wade, Ryckie G; Itte, Vinay; Rankine, James J; Ridgway, John P; Bourke, Grainne

2018-03-01

Identification of root avulsions is of critical importance in traumatic brachial plexus injuries because it alters the reconstruction and prognosis. Pre-operative magnetic resonance imaging is gaining popularity, but there is limited and conflicting data on its diagnostic accuracy for root avulsion. This cohort study describes consecutive patients requiring brachial plexus exploration following trauma between 2008 and 2016. The index test was magnetic resonance imaging at 1.5 Tesla and the reference test was operative exploration of the supraclavicular plexus. Complete data from 29 males was available. The diagnostic accuracy of magnetic resonance imaging for root avulsion(s) of C5-T1 was 79%. The diagnostic accuracy of a pseudomeningocoele as a surrogate marker of root avulsion(s) of C5-T1 was 68%. We conclude that pseudomeningocoles were not a reliable sign of root avulsion and magnetic resonance imaging has modest diagnostic accuracy for root avulsions in the context of adult traumatic brachial plexus injuries. III.

Hand Function in Children with an Upper Brachial Plexus Birth Injury: Results of the Nine-Hole Peg Test

ERIC Educational Resources Information Center

Immerman, Igor; Alfonso, Daniel T.; Ramos, Lorna E.; Grossman, Leslie A.; Alfonso, Israel; Ditaranto, Patricia; Grossman, John A. I.

2012-01-01

Aim: The aim of this study was to evaluate hand function in children with Erb upper brachial plexus palsy. Method: Hand function was evaluated in 25 children (eight males; 17 females) with a diagnosed upper (C5/C6) brachial plexus birth injury. Of these children, 22 had undergone primary nerve reconstruction and 13 of the 25 had undergone…

MULTILEVEL ISCHEMIA IN DISORGANIZATION OF THE RETINAL INNER LAYERS ON PROJECTION-RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Onishi, Alex C; Ashraf, Mohammed; Soetikno, Brian T; Fawzi, Amani A

2018-04-10

To examine the relationship between ischemia and disorganization of the retinal inner layers (DRIL). Cross-sectional retrospective study of 20 patients (22 eyes) with diabetic retinopathy presenting to a tertiary academic referral center, who had DRIL on structural optical coherence tomography (OCT) using Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) and OCT angiography with XR Avanti (Optovue Inc, Fremont, CA) on the same day. Optical coherence tomography angiography images were further processed to remove flow signal projection artifacts using a software algorithm adapted from recent studies. Retinal capillary perfusion in the superficial capillary plexuses, middle capillary plexuses, and deep capillary plexuses, as well as integrity of the photoreceptor lines on OCT was compared in areas with DRIL to control areas without DRIL in the same eye. Qualitative assessment of projection-resolved OCT angiography of eyes with DRIL on structural OCT demonstrated significant perfusion deficits compared with adjacent control areas (P < 0.001). Most lesions (85.7%) showed superimposed superficial capillary plexus and/or middle capillary plexus nonperfusion in addition to deep capillary plexus nonflow. Areas of DRIL were significantly associated with photoreceptor disruption (P = 0.035) compared with adjacent DRIL-free areas. We found that DRIL is associated with multilevel retinal capillary nonperfusion, suggesting an important role for ischemia in this OCT phenotype.

Region-specific expression and hormonal regulation of the first exon variants of rat prolactin receptor mRNA in rat brain and anterior pituitary gland.

PubMed

Nogami, H; Hoshino, R; Ogasawara, K; Miyamoto, S; Hisano, S

2007-08-01

Recent studies have revealed the occurrence of five first exon variants of the rat prolactin receptor mRNA, suggesting that multiple promoters direct prolactin receptor transcription in response to different regulatory factors. In the present study, regional expression of these first exon variants, as well as two prolactin receptor subtypes generated by alternative splicing, was examined in the brains and anterior pituitary glands of female rats. Expression of the long-form was detected in the choroid plexus, hypothalamus, hippocampus, cerebral cortex and anterior pituitary gland, whereas the short form was detected only in the choroid plexus. E1-3 mRNA, a first exon variant, was detected in the choroid plexus, hypothalamus, and anterior pituitary gland, whereas E1-4 was detected only in the choroid plexus. Other variants were not detectable by the polymerase chain reaction protocol employed in this study. Ovariectomy increased the short form in the choroid plexus and the E1-3 expression in the choroid plexus and pituitary gland, but changes in the long-form and E1-4 expression were minimal. Replacement of oestrogens and prolactin suggest that oestrogens down-regulate E1-3 expression in the choroid plexus and pituitary gland, and that the negative effect of oestrogen is mediated by prolactin in the pituitary gland. The present results revealed the region-specific promoter usage in prolactin receptor mRNA transcription, as well as the involvement of oestrogens in the regulation of E1-3 mRNA expression in the brain and pituitary gland.

Injury to the Lumbar Plexus and its Branches After Lateral Fusion Procedures: A Cadaver Study.

PubMed

Grunert, Peter; Drazin, Doniel; Iwanaga, Joe; Schmidt, Cameron; Alonso, Fernando; Moisi, Marc; Chapman, Jens R; Oskouian, Rod J; Tubbs, Richard Shane

2017-09-01

Neurologic deficits from lumbar plexus nerve injuries commonly occur in patients undergoing lateral approaches. However, it is not yet clear what types of injury occur, where anatomically they are located, or what mechanism causes them. We aimed to study 1) the topographic anatomy of lumbar plexus nerves and their injuries in human cadavers after lateral transpsoas approaches to the lumbar spine, 2) the structural morphology of those injuries, and 3) the topographic anatomy of the lumbar plexus throughout the mediolateral approach corridor. Fifteen adult fresh frozen cadaveric torsos (26 sides) underwent lateral approaches (L1-L5) by experienced lateral spine surgeons. The cadavers were subsequently opened and the entire plexus dissected and examined for nerve injuries. The topographic anatomy of the lumbar plexus and its branches, their injuries, and the morphology of these injuries were documented. Fifteen injuries were found with complete or partial nerve transections (Sunderland IV and V). Injuries were found throughout the mediolateral approach corridor. At L1/2, the iliohypogastric, ilioinguinal, and subcostal nerves were injured within the psoas major muscle, the retroperitoneal space, or the outer abdominal muscles and subcutaneous tissues. Genitofemoral nerve injuries were found in the retroperitoneal space. Nerve root injuries occurred within the retroperitoneal space and psoas muscle. Femoral nerve injuries were found only within the psoas major muscle. No obturator nerve injuries occurred. Lateral approaches can lead to structural nerve damage. Knowledge of the complex plexus anatomy, specifically its mediolateral course, is critical to avoid approach-related injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Postfixed brachial plexus radiculopathy due to thoracic disc herniation in a collegiate wrestler: a case report.

PubMed

Kuzma, Scott A; Doberstein, Scott T; Rushlow, David R

2013-01-01

To present the unique case of a collegiate wrestler with C7 neurologic symptoms due to T1-T2 disc herniation. A 23-year-old male collegiate wrestler injured his neck in a wrestling tournament match and experienced pain, weakness, and numbness in his left upper extremity. He completed that match and 1 additional match that day with mild symptoms. Evaluation by a certified athletic trainer 6 days postinjury showed radiculopathy in the C7 distribution of his left upper extremity. He was evaluated further by the team physician, a primary care physician, and a neurosurgeon. Cervical spine injury, stinger/burner, peripheral nerve injury, spinal cord injury, thoracic outlet syndrome, brachial plexus radiculopathy. The patient initially underwent nonoperative management with ice, heat, massage, electrical stimulation, shortwave diathermy, and nonsteroidal anti-inflammatory drugs without symptom resolution. Cervical spine radiographs were negative for bony pathologic conditions. Magnetic resonance imaging showed evidence of T1-T2 disc herniation. The patient underwent surgery to resolve the symptoms and enable him to participate for the remainder of the wrestling season. Whereas brachial plexus radiculopathy commonly is seen in collision sports, a postfixed brachial plexus in which the T2 nerve root has substantial contribution to the innervation of the upper extremity is a rare anatomic variation with which many health care providers are unfamiliar. The injury sustained by the wrestler appeared to be C7 radiculopathy due to a brachial plexus traction injury. However, it ultimately was diagnosed as radiculopathy due to a T1-T2 thoracic intervertebral disc herniation causing impingement of a postfixed brachial plexus and required surgical intervention. Athletic trainers and physicians need to be aware of the anatomic variations of the brachial plexus when evaluating and caring for patients with suspected brachial plexus radiculopathies.

Comparisons Between Histology and Optical Coherence Tomography Angiography of the Periarterial Capillary-Free Zone.

PubMed

Balaratnasingam, Chandrakumar; An, Dong; Sakurada, Yoichi; Lee, Cecilia S; Lee, Aaron Y; McAllister, Ian L; Freund, K Bailey; Sarunic, Marinko; Yu, Dao-Yi

2018-05-01

To use the capillary-free zone along retinal arteries, a physiologic area of superficial avascularization, as an anatomic paradigm to investigate the reliability of optical coherence tomography angiography (OCTA) for visualizing the deep retinal circulation. Validity analysis and laboratory investigation. Five normal human donor eyes (mean age 69.8 years) were perfusion-labeled with endothelial antibodies and the capillary networks of the perifovea were visualized using confocal scanning laser microscopy. Regions of the capillary-free zone along the retinal artery were imaged using OCTA in 16 normal subjects (age range 24-51 years). Then, 3 × 3-mm scans were acquired using the RTVue XR Avanti (ver. 2016.1.0.26; Optovue, Inc, Fremont, California, USA), PLEX Elite 9000 (ver. 1.5.0.15909; Zeiss Meditec, Inc, Dublin, California, USA), Heidelberg Spectralis OCT2 (Family acquisition module 6.7.21.0; Heidelberg Engineering, Heidelberg, Germany), and DRI-OCT Triton (Ver. 1.1.1; Topcon Corp, Tokyo, Japan). Images of the superficial plexus, deep vascular plexus, and a slab containing all vascular plexuses were generated using manufacturer-recommended default settings. Comparisons between histology and OCTA were performed. Histologic analysis revealed that the capillary-free zone along the retinal artery was confined to the plane of the superficial capillary plexus and did not include the intermediate and deep capillary plexuses. Images derived from OCTA instruments demonstrated a prominent capillary-free zone along the retinal artery in slabs of the superficial plexus, deep plexus, and all capillary plexuses. The number of deep retinal capillaries seen in the capillary-free zone was significantly greater on histology than on OCTA (P < .001). Using the capillary-free zone as an anatomic paradigm, we show that the deep vascular beds of the retina are not completely visualized using OCTA. This may be a limitation of current OCTA techniques. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunoreactivity for GABA, GAD65, GAD67 and Bestrophin-1 in the meninges and the choroid plexus: implications for non-neuronal sources for GABA in the developing mouse brain.

PubMed

Tochitani, Shiro; Kondo, Shigeaki

2013-01-01

Neural progenitors in the developing neocortex, neuroepithelial cells and radial glial cells, have a bipolar shape with a basal process contacting the basal membrane of the meninge and an apical plasma membrane facing the lateral ventricle, which the cerebrospinal fluid is filled with. Recent studies revealed that the meninges and the cerebrospinal fluid have certain roles to regulate brain development. γ-aminobutyric acid (GABA) is a neurotransmitter which appears first during development and works as a diffusible factor to regulate the properties of neural progenitors. In this study, we examined whether GABA can be released from the meninges and the choroid plexus in the developing mouse brain. Immunohistochemical analyses showed that glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67), both of which are GABA-synthesizing enzymes, are expressed in the meninges. The epithelial cells in the choroid plexus express GAD65. GABA immunoreactivity could be observed beneath the basal membrane of the meninge and in the epithelial cells of the choroid plexus. Expression analyses on Bestrophin-1, which is known as a GABA-permeable channel in differentiated glial cells, suggested that the cells in the meninges and the epithelial cells in the choroid plexus have the channels able to permeate non-synaptic GABA into the extracellular space. Further studies showed that GAD65/67-expressing meningeal cells appear in a manner with rostral to caudal and lateral to dorsal gradient to cover the entire neocortex by E14.5 during development, while the cells in the choroid plexus in the lateral ventricle start to express GAD65 on E11-E12, the time when the choroid plexus starts to develop in the developing brain. These results totally suggest that the meninges and the choroid plexus can work as non-neuronal sources for ambient GABA which can modulate the properties of neural progenitors during neocortical development.

Immunoreactivity for GABA, GAD65, GAD67 and Bestrophin-1 in the Meninges and the Choroid Plexus: Implications for Non-Neuronal Sources for GABA in the Developing Mouse Brain

PubMed Central

Tochitani, Shiro; Kondo, Shigeaki

2013-01-01

Neural progenitors in the developing neocortex, neuroepithelial cells and radial glial cells, have a bipolar shape with a basal process contacting the basal membrane of the meninge and an apical plasma membrane facing the lateral ventricle, which the cerebrospinal fluid is filled with. Recent studies revealed that the meninges and the cerebrospinal fluid have certain roles to regulate brain development. γ-aminobutyric acid (GABA) is a neurotransmitter which appears first during development and works as a diffusible factor to regulate the properties of neural progenitors. In this study, we examined whether GABA can be released from the meninges and the choroid plexus in the developing mouse brain. Immunohistochemical analyses showed that glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67), both of which are GABA-synthesizing enzymes, are expressed in the meninges. The epithelial cells in the choroid plexus express GAD65. GABA immunoreactivity could be observed beneath the basal membrane of the meninge and in the epithelial cells of the choroid plexus. Expression analyses on Bestrophin-1, which is known as a GABA-permeable channel in differentiated glial cells, suggested that the cells in the meninges and the epithelial cells in the choroid plexus have the channels able to permeate non-synaptic GABA into the extracellular space. Further studies showed that GAD65/67-expressing meningeal cells appear in a manner with rostral to caudal and lateral to dorsal gradient to cover the entire neocortex by E14.5 during development, while the cells in the choroid plexus in the lateral ventricle start to express GAD65 on E11–E12, the time when the choroid plexus starts to develop in the developing brain. These results totally suggest that the meninges and the choroid plexus can work as non-neuronal sources for ambient GABA which can modulate the properties of neural progenitors during neocortical development. PMID:23437266

Evaluation of macular and peripapillary vessel flow density in eyes with no known pathology using optical coherence tomography angiography.

PubMed

Hassan, Muhammad; Sadiq, Mohammad Ali; Halim, Muhammad Sohail; Afridi, Rubbia; Soliman, Mohamed K; Sarwar, Salman; Agarwal, Aniruddha; Do, Diana V; Nguyen, Quan Dong; Sepah, Yasir Jamal

2017-01-01

To assess normal vessel flow density (VFD) in macular and peripapillary regions of eyes with no known ocular pathology using optical coherence tomography angiography (OCTA). AngioVue (Optovue, Fremont, CA, USA) was used to capture OCTA images. A 3 × 3 mm grid and a 4.5 × 4.5 mm grid was used to scan parafoveal and peripapillary regions, respectively. ReVue software was utilized to measure VFD in five sectors within the inner two circles of ETDRS grid in macular region and correlated to retinal thickness of same sectors. At optic disc, VFD was calculated in six sectors based on Garway-Heath map. Area and morphology of foveal avascular zone (FAZ) was correlated with VFD in central 1 mm. The influence of myopia on mean VFD was also assessed. Twenty-four eyes (mean age: 30 years) were analyzed. Mean VFD in macular sectors was 43.5 (±4.5) and 45.8 (±5.0) % in superficial and deep retinal plexuses, respectively. Mean VFD was significantly higher in deep retinal plexus compared to superficial retinal plexus in all sectors except central 1 mm (p < 0.05). Mean VFD in central 1 mm increases with an increase in central retinal thickness in both superficial and deep retinal plexuses (p < 0.001). Mean parafoveal VFD at level of both superficial and deep retinal plexuses decrease with an increase in spherical equivalent in myopics (p < 0.05). Mean VFD in myopics was found to be significantly lower in parafoveal region of deep retinal plexus (p < 0.05). Mean area of FAZ was 0.33 (±0.15) and 0.47 mm 2 (±0.15) in superficial and deep retinal plexuses, respectively. Area of FAZ decreases with an increase in central 1 mm thickness and foveal VFD (p < 0.001). OCTA may be used to measure VFD in macular and peripapillary regions. Vessels in the parafoveal region are more densely packed in the deep retinal plexus leading to higher VFD compared to superficial plexus. Thicker retina in fovea translates into higher foveal VFD due to more compact arrangement of retinal layers and continuity of inner nuclear layer (INL). Myopia is associated with lower VFD in parafoveal region at level of deep retinal plexuses which may explain thinning of INL in myopics.

Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muccioli, G.; Guardabassi, A.; Pattono, P.

1990-03-01

The occurrence of prolactin binding sites in some brain structures (telencephalon, ventral hypothalamus, myelencephalon, hypophysis, and choroid plexus) from Xenopus laevis (anuran amphibian) was studied by the in vitro biochemical technique. The higher binding values were obtained at the level of the choroid plexus and above all of the hypothalamus. On the bases of hormonal specificity and high affinity, these binding sites are very similar to those of prolactin receptors of classical target tissues as well as of those described by us in other structures from Xenopus. To our knowledge, the present results provide the first demonstration of the occurrencemore » of prolactin specific binding sites in Xenopus laevis choroid plexus cells.« less

Pathological Alteration in the Choroid Plexus of Alzheimer’s Disease: Implication for New Therapy Approaches

PubMed Central

Krzyzanowska, Agnieszka; Carro, Eva

2012-01-01

Morphological alterations of choroid plexus in Alzheimer’s disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide. Here, we review new evidences for AD-related changes in the choroid plexus. The data suggest that the significantly altered functions of the choroid plexus contribute to the multiparametric pathogenesis of late-onset AD. PMID:22563316

Choroid Plexus Papilloma Expansion Over 7 Years in Aicardi Syndrome

PubMed Central

Frye, Richard E.; Polling, Jon S.; Ma, Louis C. K.

2008-01-01

Choroid plexus papillomas have been reported in Aicardi syndrome. Management of these tumors is controversial because their natural progression in Aicardi syndrome has only been rarely documented. This report describes the progression of such a tumor over 7 years in a girl with Aicardi syndrome. A magnetic resonance imaging study at 2 months of age demonstrated a right ventricular mass that was consistent with a unilateral choroid plexus papilloma. The mass enlarged over the next 7 years without causing any clinically apparent symptoms, ventricular enlargement, hydrocephalus, or mass effect. The tumor was removed without change in behavior or development. The know cases of Aicardi syndrome associated with choroid plexus papillomas are reviewed. The heterogeneous nature of this lesion is highlighted. PMID:17621535

Atypical choroid plexus papilloma: spontaneous resolution of diffuse leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric cases.

PubMed

Scala, Marcello; Morana, Giovanni; Milanaccio, Claudia; Pavanello, Marco; Nozza, Paolo; Garrè, Maria Luisa

2017-09-01

Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal seeding. Postoperative chemotherapy is the recommended first-line treatment when gross-total removal is not achieved or in cases of disseminated disease. Here the authors report on 2 children with atypical choroid plexus papillomas and MRI findings of diffuse leptomeningeal enhancement at diagnosis, later presenting with spontaneous resolution of the leptomeningeal involvement after removal of the primary lesions. Observations in this report expand our knowledge about the natural history and biological behavior of these tumors and highlight the role of close neuroimaging surveillance in the management of atypical choroid plexus papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at presentation.

Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice with Colitis

PubMed Central

MacEachern, Sarah J.; Patel, Bhavik A.; Keenan, Catherine M.; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C.; Beck, Paul L.; MacNaughton, Wallace K.; Sharkey, Keith A.

2015-01-01

Background & Aims Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in the epithelial hypo-responsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulphonic acid- or dextran sodium sulfate-induced colitis and in Il10−/− mice. Methods Electrically-evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10−/− mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen and blood of mice. Results Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared to mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulphonic acid -induced colitis and associated bacterial translocation. Conclusions Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation. PMID:25865048

Spatial Noise in Coupling Strength and Natural Frequency within a Pacemaker Network; Consequences for Development of Intestinal Motor Patterns According to a Weakly Coupled Phase Oscillator Model

PubMed Central

Parsons, Sean P.; Huizinga, Jan D.

2016-01-01

Pacemaker activities generated by networks of interstitial cells of Cajal (ICC), in conjunction with the enteric nervous system, orchestrate most motor patterns in the gastrointestinal tract. It was our objective to understand the role of network features of ICC associated with the myenteric plexus (ICC-MP) in the shaping of motor patterns of the small intestine. To that end, a model of weakly coupled oscillators (oscillators influence each other's phase but not amplitude) was created with most parameters derived from experimental data. The ICC network is a uniform two dimensional network coupled by gap junctions. All ICC generate pacemaker (slow wave) activity with a frequency gradient in mice from 50/min at the proximal end of the intestine to 40/min at the distal end. Key features of motor patterns, directly related to the underlying pacemaker activity, are frequency steps and dislocations. These were accurately mimicked by reduction of coupling strength at a point in the chain of oscillators. When coupling strength was expressed as a product of gap junction density and conductance, and gap junction density was varied randomly along the chain (i.e., spatial noise) with a long-tailed distribution, plateau steps occurred at pointsof low density. As gap junction conductance was decreased, the number of plateaus increased, mimicking the effect of the gap junction inhibitor carbenoxolone. When spatial noise was added to the natural interval gradient, as gap junction conductance decreased, the number of plateaus increased as before but in addition the phase waves frequently changed direction of apparent propagation, again mimicking the effect of carbenoxolone. In summary, key features of the motor patterns that are governed by pacemaker activity may be a direct consequence of biological noise, specifically spatial noise in gap junction coupling and pacemaker frequency. PMID:26869875

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS.

PubMed

Badawy, Gamal; Reinecke, Manfred

2003-03-01

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.

Effects of cholera toxin on the potential difference and motor responses induced by distension in the rat proximal small intestine in vivo.

PubMed

Kordasti, Shirin; Sapnara, Maria; Thomas, Evan A; Lindstrom, Erik; Forsman, Mikael; Bornstein, Joel C; Sjövall, Henrik

2006-05-01

Cholera toxin (CT) may induce uncontrolled firing in recurrent networks of secretomotor neurons in the submucous plexus. This hypothesis was tested in chloralose-anesthetized rats in vivo. The secretory reflex response to graded intestinal distension was measured with or without prior exposure to luminal CT. The transmural potential difference (PD) was used as a marker for electrogenic chloride secretion. In controls, distension increased PD, and this response was reduced by the neural blocker tetrodotoxin given serosally and the vasoactive intestinal peptide (VIP) receptor antagonist [4Cl-d-Phe(6),Leu(17)]VIP (2 mug.min(-1).kg(-1) iv) but unaffected by the serotonin 5-HT(3) receptor antagonist granisetron, by the nicotinic receptor antagonist hexamethonium, by the muscarinic receptor antagonist atropine, or by the cyclooxygenase inhibitor indomethacin. Basal PD increased significantly with time in CT-exposed segments, an effect blocked by granisetron, by indomethacin, and by [4Cl-d-Phe(6),Leu(17)]VIP but not by hexamethonium or atropine. In contrast, once the increased basal PD produced by CT was established, [4Cl-d-Phe(6),Leu(17)]VIP and indomethacin had no significant effect, whereas granisetron and hexamethonium markedly depressed basal PD. CT significantly reduced the increase in PD produced by distension, an effect reversed by granisetron, indomethacin, and atropine. CT also activated a specific motility response to distension, repeated cluster contractions, but only in animals pretreated with granisetron, indomethacin, or atropine. These data are compatible with the hypothesis that CT induces uncontrolled activity in submucous secretory networks. Development of this state depends on 5-HT(3) receptors, VIP receptors, and prostaglandin synthesis, whereas its maintenance depends on 5-HT(3) and nicotinic receptors but not VIP receptors. The motility effects of CT (probably reflecting myenteric activity) are partially suppressed via a mechanism involving 5-HT(3) and muscarinic receptors and prostaglandin synthesis.

Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype.

PubMed

Kulkarni, Subhash; Zou, Bende; Hanson, Jesse; Micci, Maria-Adelaide; Tiwari, Gunjan; Becker, Laren; Kaiser, Martin; Xie, Xinmin Simon; Pasricha, Pankaj Jay

2011-10-01

Recent studies have explored the potential of central nervous system-derived neural stem cells (CNS-NSC) to repopulate the enteric nervous system. However, the exact phenotypic fate of gut-transplanted CNS-NSC has not been characterized. The aim of this study was to investigate the effect of the gut microenvironment on phenotypic fate of CNS-NSC in vitro. With the use of Transwell culture, differentiation of mouse embryonic CNS-NSC was studied when cocultured without direct contact with mouse intestinal longitudinal muscle-myenteric plexus preparations (LM-MP) compared with control noncocultured cells, in a differentiating medium. Differentiated cells were analyzed by immunocytochemistry and quantitative RT-PCR to assess the expression of specific markers and by whole cell patch-clamp studies for functional characterization of their phenotype. We found that LM-MP cocultured cells had a significant increase in the numbers of cells that were immune reactive against the panneuronal marker β-tubulin, neurotransmitters neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and neuropeptide vasoactive intestinal peptide (VIP) and showed an increase in expression of these genes, compared with control cells. Whole cell patch-clamp analysis showed that coculture with LM-MP decreases cell excitability and reduces voltage-gated Na(+) currents but significantly enhances A-current and late afterhyperpolarization (AHP) and increases the expression of the four AHP-generating Ca(2+)-dependent K(+) channel genes (KCNN), compared with control cells. In a separate experiment, differentiation of LM-MP cocultured CNS-NSC produced a significant increase in the numbers of cells that were immune reactive against the neurotransmitters nNOS, ChAT, and the neuropeptide VIP compared with CNS-NSC differentiated similarly in the presence of neonatal brain tissue. Our results show that the gut microenvironment induces CNS-NSC to produce neurons that share some of the characteristics of classical enteric neurons, further supporting the therapeutic use of these cells for gastrointestinal disorders.

L-689,660, a novel cholinomimetic with functional selectivity for M1 and M3 muscarinic receptors.

PubMed Central

Hargreaves, R. J.; McKnight, A. T.; Scholey, K.; Newberry, N. R.; Street, L. J.; Hutson, P. H.; Semark, J. E.; Harley, E. A.; Patel, S.; Freedman, S. B.

1992-01-01

1. L-689,660, 1-azabicyclo[2.2.2]octane, 3-(6-chloropyrazinyl)maleate, a novel cholinomimetic, demonstrated high affinity binding (pKD (apparent) 7.42) at rat cerebral cortex muscarinic receptors. L-689,660 had a low ratio (34) of pKD (apparent) values for the displacement of binding of the antagonist ([3H]-N-methylscopolamine ([3H]-NMS) compared with the displacement of the agonist [3H]-oxotremorine-M ([3H]-Oxo-M), in rat cerebral cortex. Low NMS/Oxo-M ratios have been shown previously to be a characteristic of compounds that are low efficacy partial agonists with respect to stimulation of phosphatidyl inositol turnover in the cerebral cortex. 2. L-689,660 showed no muscarinic receptor subtype selectivity in radioligand binding assays but showed functional selectivity in pharmacological assays. At M1 muscarinic receptors in the rat superior cervical ganglion, L-689,660 was a potent (pEC50 7.3 +/- 0.2) full agonist in comparison with (+/-)-muscarine. At M3 receptors in the guinea-pig ileum myenteric plexus-longitudinal muscle or in trachea, L-689,660 was again a potent agonist (pEC50 7.5 +/- 0.2 and 7.7 +/- 0.3 respectively) but had a lower maximum response than carbachol. In contrast L-689,660 was an antagonist at M2 receptors in guinea-pig atria (pA2 7.2 (95% confidence limits 7, 7.4)) and at muscarinic autoreceptors in rat hippocampal slices. 3. The putative M1-selective muscarinic agonist, AF102B (cis-2-methylspiro-(1,3-oxathiolane 5,3')-quinuclidine hydrochloride) was found to have a profile similar to L-689,660 but had up to 100 times less affinity in binding and functional assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1422595

FGF2 deficit during development leads to specific neuronal cell loss in the enteric nervous system.

PubMed

Hagl, Cornelia Irene; Wink, Elvira; Scherf, Sabrina; Heumüller-Klug, Sabine; Hausott, Barbara; Schäfer, Karl-Herbert

2013-01-01

The largest part of the peripheral nervous system is the enteric nervous system (ENS). It consists of an intricate network of several enteric neuronal subclasses with distinct phenotypes and functions within the gut wall. The generation of these enteric phenotypes is dependent upon appropriate neurotrophic support during development. Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2) play an important role in the differentiation and function of the ENS. A lack of GDNF or its receptor (Ret) causes intestinal aganglionosis in mice, while fibroblast growth factor receptor signaling antagonist is identified as regulating proteins in the GDNF/Ret signaling in the developing ENS. Primary myenteric plexus cultures and wholemount preparations of wild type (WT) and FGF2-knockout mice were used to analyze distinct enteric subpopulations. Fractal dimension (D) as a measure of self-similarity is an excellent tool to analyze complex geometric shape and was applied to classify the subclasses of enteric neurons concerning their individual morphology. As a consequence of a detailed analysis of subpopulation variations, wholemount preparations were stained for the calcium binding proteins calbindin and calretinin. The fractal analysis showed a reliable consistence of subgroups with different fractal dimensions (D) in each culture investigated. Seven different neuronal subtypes could be differentiated according to a rising D. Within the same D, the neurite length revealed significant differences between wild type and FGF2-knockout cultures, while the subclass distribution was also altered. Depending on the morphological characteristics, the reduced subgroup was supposed to be a secretomotor neuronal type, which could be confirmed by calbindin and calretinin staining of the wholemount preparations. These revealed a reduction up to 40 % of calbindin-positive neurons in the FGF2-knockout mouse. We therefore consider FGF2 playing a more important role in the fine-tuning of the ENS during development as previously assumed.

Clustering of Ca2+ transients in interstitial cells of Cajal defines slow wave duration

PubMed Central

Drumm, Bernard T.; Hennig, Grant W.; Battersby, Matthew J.; Sung, Tae Sik

2017-01-01

Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca2+-activated Cl− channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca2+ regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca2+ transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca2+ sensor, GCaMP3, in ICC. Ca2+ transients in ICC-MY display a complex firing pattern caused by localized Ca2+ release events arising from multiple sites in cell somata and processes. Ca2+ transients are clustered within the time course of slow waves but fire asynchronously during these clusters. The durations of Ca2+ transient clusters (CTCs) correspond to slow wave durations (plateau phase). Simultaneous imaging and intracellular electrical recordings revealed that the upstroke depolarization of slow waves precedes clusters of Ca2+ transients. Summation of CTCs results in relatively uniform Ca2+ responses from one slow wave to another. These Ca2+ transients are caused by Ca2+ release from intracellular stores and depend on ryanodine receptors as well as amplification from IP3 receptors. Reduced extracellular Ca2+ concentrations and T-type Ca2+ channel blockers decreased the number of firing sites and firing probability of Ca2+ transients. In summary, the fundamental electrical events of small intestinal muscles generated by ICC-MY depend on asynchronous firing of Ca2+ transients from multiple intracellular release sites. These events are organized into clusters by Ca2+ influx through T-type Ca2+ channels to sustain activation of ANO1 channels and generate the plateau phase of slow waves. PMID:28592421

Differential expression of GSK3β and pS9GSK3β in normal human tissues: can pS9GSK3β be an epithelial marker?

PubMed

Lee, Hojung; Ro, Jae Y

2015-01-01

Glycogen synthase kinase 3β (GSK3β) and phosphorylated GSK3β at Ser9 (pS9GSK3β) are crucial in cellular proliferation and metabolism. GSK3β and pS9GSK3β are deregulated in many diseases including tumors. Data on altered expression of GSK3β and pS9GSK3β are mainly limited to tumor tissues, thus the expression of GSK3β and pS9GSK3β in normal human tissue has been largely unknown. Thus, we examined the immunohistochemical localization of GSK3β and pS9GSK3β in human fetal and adult tissues, and also compared the expression pattern of GSK3β and pS9GSK3β with that of the CK7 and CK20. We found GSK3β expression in neurons of brain, myenteric plexus in gastrointestinal tract, squamous epithelium of skin, and mammary gland. The expression of pS9GSK3β was restricted to the epithelial cells of breast and pancreaticobiliary duct, distal nephron of kidney, gastrointestinal tract, fallopian tube, epididymis, secretory cell of prostatic gland, and umbrella cell of urinary tract. The staining pattern of pS9GSK3β and CK7 was overlapped in most organs except for gastrointestinal tract where CK7 was negative and CK20 was positive. Our results show that the expression of GSK3β may be associated with differentiation of ectodermal derived tissues and pS9GSK3β with that of epithelial cells of endodermal derived tissues in human. In addition, the expression of pS9GSK3β in the selective epithelial cells may indicate its association with secretory or barrier function of specific cells and may serve as another immunohistochemical marker for epithelial cells.

SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions.

PubMed

Chen, Lei L; Zhu, Jing; Schumacher, Jonathan; Wei, Chongjuan; Ramdas, Latha; Prieto, Victor G; Jimenez, Arnie; Velasco, Marco A; Tripp, Sheryl R; Andtbacka, Robert H I; Gouw, Launce; Rodgers, George M; Zhang, Liansheng; Chan, Benjamin K; Cassidy, Pamela B; Benjamin, Robert S; Leachman, Sancy A; Frazier, Marsha L

2017-01-01

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions

PubMed Central

Zhu, Jing; Schumacher, Jonathan; Wei, Chongjuan; Ramdas, Latha; Prieto, Victor G.; Jimenez, Arnie; Velasco, Marco A.; Tripp, Sheryl R.; Andtbacka, Robert H. I.; Gouw, Launce; Rodgers, George M.; Zhang, Liansheng; Chan, Benjamin K.; Cassidy, Pamela B.; Benjamin, Robert S.; Leachman, Sancy A.; Frazier, Marsha L.

2017-01-01

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation. PMID:28880927

Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve.

PubMed

Uemura, Norihito; Yagi, Hisashi; Uemura, Maiko T; Hatanaka, Yusuke; Yamakado, Hodaka; Takahashi, Ryosuke

2018-05-11

Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc. We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology. The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model. These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.

Facilitation and inhibition by capsaicin of cholinergic neurotransmission in the guinea-pig small intestine.

PubMed

Geber, Christian; Mang, Christian F; Kilbinger, Heinz

2006-01-01

The effects of capsaicin on [3H]acetylcholine release and muscle contraction were studied on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum preincubated with [3H]choline. Capsaicin concentration-dependently increased both basal [3H]acetylcholine release (pEC50 7.0) and muscle tone (pEC50 6.1). The facilitatory effects of capsaicin were antagonized by 1 microM capsazepine (pK (B) 7.0 and 7.6), and by the combined blockade of NK1 and NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 microM). This suggests that stimulation by capsaicin of TRPV1 receptors on primary afferent fibres causes a release of tachykinins which, in turn, mediate via NK1 and NK3 receptors an increase in acetylcholine release. The capsaicin-induced acetylcholine release was significantly enhanced by the NO synthase inhibitor L-NG-nitroarginine (100 microM). This indicates that tachykinins released from sensory neurons also stimulate nitrergic neurons and thus lead, via NO release, to inhibition of acetylcholine release. Capsaicin concentration-dependently reduced the electrically-evoked [3H]acetylcholine release (pEC50 6.4) and twitch contractions (pEC50 5.9). The inhibitory effects were not affected by either capsazepine, NK1 and NK3 receptor antagonists, the cannabinoid CB1 antagonist SR141716A or by L-NG-nitroarginine. Desensitization of TRPV1 receptors by a short exposure to 3 microM capsaicin abolished the facilitatory responses to a subsequent administration, but did not modify the inhibitory effects. In summary, capsaicin has a dual effect on cholinergic neurotransmission. The facilitatory effect is indirect and involves tachykinin release and excitation of NK1 and NK3 receptors on cholinergic neurons. The inhibition of acetylcholine release may be due to a decrease of Ca2+ influx into cholinergic neurons.

Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice With Colitis.

PubMed

MacEachern, Sarah J; Patel, Bhavik A; Keenan, Catherine M; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C; Beck, Paul L; MacNaughton, Wallace K; Sharkey, Keith A

2015-08-01

Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in epithelial hyporesponsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulfonic acid- or dextran sodium sulfate-induced colitis and in Il10(-/-) mice. Electrically evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10(-/-) mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen, and blood of mice. Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared with mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulfonic acid-induced colitis and associated bacterial translocation. Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1 simultaneously to modulate colonic motility and visceral sensation in the mouse: A pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT).

PubMed

Bashashati, M; Fichna, J; Piscitelli, F; Capasso, R; Izzo, A A; Sibaev, A; Timmermans, J-P; Cenac, N; Vergnolle, N; Di Marzo, V; Storr, M

2017-12-01

Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied. The colonic levels of endocannabinoids and fatty acid amides were measured. CB1-positive neurons exhibited TRPV1; only some TRPV1 positive neurons did not express CB1. CB1 and FAAH did not colocalize. AA-5-HT (100 nM-10 μM) decreased colonic contractility by ~60%; this effect was abolished by TRPV1 antagonist 5'-IRTX, but not by CB1 antagonist, SR141716. AA-5-HT (1 μM-10 μM) inhibited EJP by ~30% and IJPs by ~50%. The effects of AA-5-HT on junction potentials were reversed by SR141716 and 5`-IRTX. AA-5-HT (20 mg/kg; i.p.) inhibited colonic propulsion by ~30%; SR141716 but not 5`-IRTX reversed this effect. AA-5-HT decreased VMR by ~50%-60%; these effects were not blocked by SR141716 or 5`-IRTX. AA-5-HT increased AEA in the colon. The effects of AA-5-HT on visceral sensation and colonic motility are differentially mediated by CB1, TRPV1 and non-CB1/TRPV1 mechanisms, possibly reflecting the distinct neuromodulatory roles of endocannabinoid and endovanilloid FAAH substrates in the mouse intestine. © 2017 John Wiley & Sons Ltd.

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

PubMed

Peiris, Madusha; Hockley, James Rf; Reed, David E; Smith, Ewan St John; Bulmer, David C; Blackshaw, L Ashley

2017-01-01

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The K V 7 family (K V 7.1-K V 7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral K V 7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of K V 7 subtypes (K V 7.3 and K V 7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the K V 7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B 2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0-80 mmHg) in a concentration-dependent manner, whereas the K V 7 blocker XE991 potentiated such responses. In human bowel tissues, K V 7.3 and K V 7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that K V 7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted K V 7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

PubMed

Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

2016-10-15

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Food restriction enhances oxidative status in aging rats with neuroprotective effects on myenteric neuron populations in the proximal colon.

PubMed

Schoffen, João Paulo Ferreira; Santi Rampazzo, Ana Paula; Cirilo, Carla Possani; Zapater, Mariana Cristina Umada; Vicentini, Fernando Augusto; Comar, Jurandir Fernando; Bracht, Adelar; Natali, Maria Raquel Marçal

2014-03-01

Food restriction may slow the aging process by increasing the levels of antioxidant defenses and reducing cell death. We evaluated the effects of food restriction on oxidative and nutritional status, myenteric cell populations, and the colonic muscle layer in aging rats. Wistar rats were distributed into control groups (7, 12, and 23months of age) and subjected to food restriction (50% of normal diet) beginning at 7months of age. The animals were sacrificed, and blood was collected to evaluate its components and markers of oxidative status, including thiobarbituric acid-reactive substances, reduced glutathione, catalase, glutathione peroxidase, and total antioxidant capacity. The proximal colon was collected to evaluate HuC/D and neuronal nitric oxide synthase (nNOS)-positive and -negative myenteric neurons, S-100 glial cells, and the muscle layer. Age negatively affected oxidative status in the animals, which also increased the levels of total cholesterol, protein, and globulins and increased the thickness of the muscle layer. Aging also reduced the number and hypertrophied glial cell bodies, HuC/D neurons, and nNOS-negative and -positive neurons. An improvement was observed in oxidative status and the levels of total cholesterol and triglycerides with food restriction, which also provided neuroprotection of the intrinsic innervation. However, food restriction accentuated the loss of enteric glia and caused hypertrophy in the muscle layer at 23months. Food restriction improved oxidative and nutritional status in rats and protected HuC/D neurons and nNOS-negative and -positive neurons against neuronal loss. Nevertheless, food restriction caused morphoquantitative changes in glial cell populations, with possible interference with colonic neuromuscular control. Copyright © 2014 Elsevier Inc. All rights reserved.

The Prevalence, Rate of Progression, and Treatment of Elbow Flexion Contracture in Children with Brachial Plexus Birth Palsy

PubMed Central

Sheffler, Lindsey C.; Lattanza, Lisa; Hagar, Yolanda; Bagley, Anita; James, Michelle A.

2012-01-01

Background: Elbow flexion contracture is a well-known complication of brachial plexus birth palsy that adversely affects upper-extremity function. The prevalence, risk factors, and rate of progression of elbow flexion contracture associated with brachial plexus birth palsy have not been established, and the effectiveness of nonoperative treatment involving nighttime splinting or serial casting has not been well studied. Methods: The medical records of 319 patients with brachial plexus birth palsy who had been seen at our institution between 1992 and 2009 were retrospectively reviewed to identify patients with an elbow flexion contracture (≥10°). The chi-square test for trend and the Kaplan-Meier estimator were used to evaluate risk factors for contracture, including age, sex, and the extent of brachial plexus involvement. Longitudinal models were used to estimate the rate of contracture progression and the effectiveness of nonoperative treatment. Results: An elbow flexion contracture was present in 48% (152) of the patients with brachial plexus birth palsy. The median age of onset was 5.1 years (range, 0.25 to 14.8 years). The contracture was ≥30° in 36% (fifty-four) of these 152 patients and was accompanied by a documented radial head dislocation in 6% (nine). The prevalence of contracture increased with increasing age (p < 0.001) but was not significantly associated with sex or with the extent of brachial plexus involvement. The magnitude of the contracture increased by 4.4% per year before treatment (p < 0.01). The magnitude of the contracture decreased by 31% when casting was performed (p < 0.01) but thereafter increased again at the same rate of 4.4% per year. The magnitude of the contracture did not improve when splinting was performed but the rate of increase thereafter decreased to <0.1% per year (p = 0.04). Conclusions: The prevalence of elbow flexion contracture in children with brachial plexus birth palsy may be greater than clinicians perceive. The prevalence increased with patient age but was not significantly affected by sex or by the extent of brachial plexus involvement. Serial casting may initially improve severe contractures, whereas nighttime splinting may prevent further progression of milder contractures. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:22398733

A Randomized Controlled Trial Examining the Effect of the Addition of the Mandibular Block to Cervical Plexus Block for Carotid Endarterectomy.

PubMed

Kavrut Ozturk, Nilgun; Kavakli, Ali Sait; Sagdic, Kadir; Inanoglu, Kerem; Umot Ayoglu, Raif

2018-04-01

Although the cervical plexus block generally provides adequate analgesia for carotid endarterectomy, pain caused by metal retractors on the inferior surface of the mandible is not prevented by the cervical block. Different pain relief methods can be performed for patients who experience discomfort in these areas. In this study, the authors evaluated the effect of mandibular block in addition to cervical plexus block on pain scores in carotid endarterectomy. A prospective, randomized, controlled trial. Training and research hospital. Patients who underwent a carotid endarterectomy. Patients scheduled for carotid endarterectomy under cervical plexus block were randomized into 2 groups: group 1 (those who did not receive a mandibular block) and group 2 (those who received a mandibular block). The main purpose of the study was to evaluate the mandibular block in addition to cervical plexus block in terms of intraoperative pain scores. Intraoperative visual analog scale scores were significantly higher in group 1 (p = 0.001). The amounts of supplemental 1% lidocaine and intraoperative intravenous analgesic used were significantly higher in group 1 (p = 0.001 and p = 0.035, respectively). Patient satisfaction scores were significantly lower in group 1 (p = 0.044). The amount of postoperative analgesic used, time to first analgesic requirement, postoperative visual analog scale scores, and surgeon satisfaction scores were similar in both groups. There was no significant difference between the groups with respect to complications. No major neurologic deficits or perioperative mortality were observed. Mandibular block in addition to cervical plexus block provides better intraoperative pain control and greater patient satisfaction than cervical plexus block alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Characterisation of Transport Mechanisms at the Developing Mouse Blood–CSF Interface: A Transcriptome Approach

PubMed Central

Liddelow, Shane A.; Temple, Sally; Møllgård, Kjeld; Gehwolf, Renate; Wagner, Andrea; Bauer, Hannelore; Bauer, Hans-Christian; Phoenix, Timothy N.; Dziegielewska, Katarzyna M.; Saunders, Norman R.

2012-01-01

Exchange mechanisms across the blood–cerebrospinal fluid (CSF) barrier in the choroid plexuses within the cerebral ventricles control access of molecules to the central nervous system, especially in early development when the brain is poorly vascularised. However, little is known about their molecular or developmental characteristics. We examined the transcriptome of lateral ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous genes identified in the adult were expressed at similar levels at E15, indicating substantial plexus maturity early in development. Some genes coding for key functions (intercellular/tight junctions, influx/efflux transporters) changed expression during development and their expression patterns are discussed in the context of available physiological/permeability results in the developing brain. Three genes: Secreted protein acidic and rich in cysteine (Sparc), Glycophorin A (Gypa) and C (Gypc), were identified as those whose gene products are candidates to target plasma proteins to choroid plexus cells. These were investigated using quantitative- and single-cell-PCR on plexus epithelial cells that were albumin- or total plasma protein-immunopositive. Results showed a significant degree of concordance between plasma protein/albumin immunoreactivity and expression of the putative transporters. Immunohistochemistry identified SPARC and GYPA in choroid plexus epithelial cells in the embryo with a subcellular distribution that was consistent with transport of albumin from blood to cerebrospinal fluid. In adult plexus this pattern of immunostaining was absent. We propose a model of the cellular mechanism in which SPARC and GYPA, together with identified vesicle-associated membrane proteins (VAMPs) may act as receptors/transporters in developmentally regulated transfer of plasma proteins at the blood–CSF interface. PMID:22457777

SPECTRAL DOMAIN VERSUS SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE RETINAL CAPILLARY PLEXUSES IN SICKLE CELL MACULOPATHY.

PubMed

Jung, Jesse J; Chen, Michael H; Frambach, Caroline R; Rofagha, Soraya; Lee, Scott S

2018-01-01

To compare the spectral domain and swept source optical coherence tomography angiography findings in two cases of sickle cell maculopathy. A 53-year-old man and a 24-year-old man both with sickle cell disease (hemoglobin SS) presented with no visual complaints; Humphrey visual field testing demonstrated asymptomatic paracentral scotomas that extended nasally in the involved eyes. Clinical examination and multimodal imaging including spectral domain and swept source optical coherence tomography, and spectral domain optical coherence tomography angiography and swept source optical coherence tomography angiography (Carl Zeiss Meditec Inc, Dublin, CA) were performed. Fundus examination of both patients revealed subtle thinning of the macula. En-face swept source optical coherence tomography confirmed the extent of the thinning correlating with the functional paracentral scotomas on Humphrey visual field. Swept source optical coherence tomography B-scan revealed multiple confluent areas of inner nuclear thinning and significant temporal retinal atrophy. En-face 6 × 6-mm spectral domain optical coherence tomography angiography of the macula demonstrated greater loss of the deep capillary plexus compared with the superficial capillary plexus. Swept source optical coherence tomography angiography 12 × 12-mm imaging captured the same macular findings and loss of both plexuses temporally outside the macula. In these two cases of sickle cell maculopathy, deep capillary plexus ischemia is more extensive within the macula, whereas both the superficial capillary plexus and deep capillary plexus are involved outside the macula likely due to the greater oxygen demands and watershed nature of these areas. Swept source optical coherence tomography angiography clearly demonstrates the angiographic extent of the disease correlating with the Humphrey visual field scotomas and confluent areas of inner nuclear atrophy.

Relationship of the lumbar plexus branches to the lumbar spine: anatomical study with application to lateral approaches.

PubMed

Tubbs, Richard Isaiah; Gabel, Brandon; Jeyamohan, Shiveindra; Moisi, Marc; Chapman, Jens R; Hanscom, R David; Loukas, Marios; Oskouian, Rod J; Tubbs, Richard Shane

2017-07-01

Injuries to the lumbar plexus during lateral approaches to the spine are not uncommon and may result in permanent deficits. However, the literature contains few studies that provide landmarks for avoiding the branches of the lumbar plexus. The present anatomical study was performed to elucidate the course of these nerves in relation to lateral approaches to the lumbar spine. This is a quantitative anatomical cadaveric study. The lumbar plexus and its branches were dissected on 12 cadaveric sides. Metal wires were laid on the nerves along their paths on the posterior abdominal wall. Fluoroscopy was performed in the anteroposterior and lateral positions. The relationships between regional bony landmarks and the branches of the lumbar plexus were observed. When viewed laterally, the greatest concentration of nerves occurred from the posteroinferior aspect of L4, inferior along the posterior one-third of the body of L5, then at the level of the sacral promontory. On the basis of our study, approaches to the anterior two-thirds of the L4 vertebra and anterior third of L5 will result in the lowest chance of lumbar plexus nerve injury. In addition, lateral muscle dissection through the psoas major should be in a superior to inferior direction in order to minimize nerve injury. Laterally, the widest corridor between branches in the abdominal wall was between the subcostal and iliohypogastric nerves. The findings of our cadaveric study provide surgeons who approach the lateral lumbar spine with data that could decrease injuries to the branches of the lumbar plexus, thus lessening patient morbidity. Copyright © 2017 Elsevier Inc. All rights reserved.

A Monte Carlo model for the internal dosimetry of choroid plexuses in nuclear medicine procedures.

PubMed

Amato, Ernesto; Cicone, Francesco; Auditore, Lucrezia; Baldari, Sergio; Prior, John O; Gnesin, Silvano

2018-05-01

Choroid plexuses are vascular structures located in the brain ventricles, showing specific uptake of some diagnostic and therapeutic radiopharmaceuticals currently under clinical investigation, such as integrin-binding arginine-glycine-aspartic acid (RGD) peptides. No specific geometry for choroid plexuses has been implemented in commercially available software for internal dosimetry. The aims of the present study were to assess the dependence of absorbed dose to the choroid plexuses on the organ geometry implemented in Monte Carlo simulations, and to propose an analytical model for the internal dosimetry of these structures for 18 F, 64 Cu, 67 Cu, 68 Ga, 90 Y, 131 I and 177 Lu nuclides. A GAMOS Monte Carlo simulation based on direct organ segmentation was taken as the gold standard to validate a second simulation based on a simplified geometrical model of the choroid plexuses. Both simulations were compared with the OLINDA/EXM sphere model. The gold standard and the simplified geometrical model gave similar dosimetry results (dose difference < 3.5%), indicating that the latter can be considered as a satisfactory approximation of the real geometry. In contrast, the sphere model systematically overestimated the absorbed dose compared to both Monte Carlo models (range: 4-50% dose difference), depending on the isotope energy and organ mass. Therefore, the simplified geometric model was adopted to introduce an analytical approach for choroid plexuses dosimetry in the mass range 2-16 g. The proposed model enables the estimation of the choroid plexuses dose by a simple bi-parametric function, once the organ mass and the residence time of the radiopharmaceutical under investigation are provided. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Transmigration of macrophages across the choroid plexus epithelium in response to the feline immunodeficiency virus

PubMed Central

Meeker, Rick B.; Bragg, D. C.; Poulton, Winona; Hudson, Lola

2013-01-01

Although lentiviruses such as human, feline and simian immunodeficiency viruses (HIV, FIV, SIV) rapidly gain access to cerebrospinal fluid (CSF), the mechanisms that control this entry are not well understood. One possibility is that the virus may be carried into the brain by immune cells that traffic across the blood–CSF barrier in the choroid plexus. Since few studies have directly examined macrophage trafficking across the blood–CSF barrier, we established transwell and explant cultures of feline choroid plexus epithelium and measured trafficking in the presence or absence of FIV. Macrophages in co-culture with the epithelium showed significant proliferation and robust trafficking that was dependent on the presence of epithelium. Macrophage migration to the apical surface of the epithelium was particularly robust in the choroid plexus explants where 3-fold increases were seen over the first 24 h. Addition of FIV to the cultures greatly increased the number of surface macrophages without influencing replication. The epithelium in the transwell cultures was also permissive to PBMC trafficking, which increased from 17 to 26% of total cells after exposure to FIV. Thus, the choroid plexus epithelium supports trafficking of both macrophages and PBMCs. FIV significantly enhanced translocation of macrophages and T cells indicating that the choroid plexus epithelium is likely to be an active site of immune cell trafficking in response to infection. PMID:22281685

Retinal-specific ATP-binding cassette transporter (ABCR/ABCA4) is expressed at the choroid plexus in rat brain.

PubMed

Bhongsatiern, Jiraganya; Ohtsuki, Sumio; Tachikawa, Masanori; Hori, Satoko; Terasaki, Tetsuya

2005-03-01

ATP-binding cassette (ABC) transporter A4 is a member of the ABC transporter subfamily A which has been reported to be exclusively expressed in the retina. In contrast, a previous report has suggested a possible relationship between ABCA4 and CNS function. The purpose of the present study was to investigate the localization of ABCA4 mRNA and protein in rat brain. In situ hybridization analysis revealed that ABCA4 mRNA was localized in the lateral ventricles. RT-PCR analysis detected ABCA4 mRNA in isolated rat choroid plexus and conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB). Furthermore, ABCA4 protein was also detected in the isolated rat choroid plexus at about 250 kDa by western blot analysis, and its apparent molecular size was reduced by N-glycosidase F treatment. These results suggest that glycosylated ABCA4 protein is expressed in rat choroid plexus epithelial cells. ABCA4 may play a role in the function of the blood-cerebrospinal fluid barrier and affect CSF conditions.

Salt-loading increases vasopressin and vasopressin 1b receptor mRNA in the hypothalamus and choroid plexus.

PubMed

Zemo, D A; McCabe, J T

2001-01-01

The choroid plexus plays a pivotal role in the production of cerebrospinal fluid (CSF). Messenger RNA (mRNA) transcripts encoding arginine vasopressin (AVP) and the vasopressin 1b receptor (V(1b)R) are found in various structures of the central nervous system, including the choroid plexus. The present study measured AVP and V(1b)R mRNA production in response to plasma hyperosmolality. Compared to rats maintained on water, 2% salt-drinking rats had increased levels of AVP and V(1b)R mRNAs in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and in the choroid plexus. The increase in V(1b)R mRNA in the SON and PVN as a result of plasma hyperosmolality may reflect changes in receptor production that, in turn, have a role in AVP autoregulation of hypothalamic magnocellular neurons. The increase of AVP and V(1b)R mRNAs in the choroid plexus further shows the involvement of AVP in the regulation of brain water content and cerebral edema. Copyright 2001 Harcourt Publishers Ltd.

Choroid plexus carcinoma with neuronal and glial differentiation in a 7-week-old male Sprague-Dawley rat.

PubMed

Inohana, Mari; Eguchi, Ayumi; Nakamura, Misato; Nagahara, Rei; Watanabe, Yosuke; Yoshida, Toshinori; Shibutani, Makoto

2018-04-18

We describe a case of choroid plexus carcinoma arising in the cerebrum of a 7-week-old male Sprague-Dawley rat. The tumor mass occupied the right lateral ventricle of the cerebrum. Histological analyses revealed that the epithelial tumor cells had proliferated in tubular, cribriform, papillary and solid growth patterns in the vicinity of the choroid plexus, with slight invasion into the cerebrum parenchyma. We divided the tumor cells into cuboidal, elongated and intermediate cells. Immunohistochemical studies showed that these tumor cells expressed relatively high levels of cytokeratin AE1/AE3, vimentin and glial fibrillary acidic proteins, and low levels of nestin, oligodendrocyte transcription factor and doublecortin proteins. The present case was diagnosed as a choroid plexus carcinoma with neuronal and glial differentiation.

Rhabdomyolysis resulting in concurrent Horner's syndrome and brachial plexopathy: a case report.

PubMed

Lee, Susan C; Geannette, Christian; Wolfe, Scott W; Feinberg, Joseph H; Sneag, Darryl B

2017-08-01

This case report describes a 29-year-old male who presented with immediate onset of Horner's syndrome and ipsilateral brachial plexopathy after sleeping with his arm dangling outside a car window for 8 h. Outside workup and imaging revealed rhabdomyolysis of the left neck musculature. Subsequent electrodiagnostic testing and high-resolution brachial plexus magnetic resonance imaging at the authors' institution attributed the Horner's syndrome and concurrent brachial plexopathy to rhabdomyolysis of the longus colli and scalene musculature, which had compressed-and consequently scar tethered-the cervical sympathetic trunk and brachial plexus. This case of co-existent Horner's syndrome and brachial plexopathy demonstrates the role of high-resolution brachial plexus MRI in diagnosing plexopathy and the importance of being familiar with plexus and paravertebral muscle anatomy.

The phrenic nerve transfer in the treatment of a septuagenarian with brachial plexus avulsion injury: a case report.

PubMed

Jiang, Ye; Lao, Jie

2018-05-01

Phrenic nerve transfer has been a well-established procedure for restoring elbow flexion function in patients with brachial plexus avulsion injury. Concerning about probably detrimental respiratory effects brought by the operation, however, stirred up quite a bit of controversy. We present a case report of the successful application of phrenic nerve as donor to reinnervate the biceps in a septuagenarian with brachial plexus avulsion injury, not accompanied with significant clinical respiratory problem.

Use of brachial plexus blockade and medetomidine-ketamine-isoflurane anaesthesia for repair of radio-ulna fracture in an adult cheetah (Acinonyx jubatus).

PubMed

Kimeli, Peter; Mogoa, Eddy M; Mwangi, Willy E; Kipyegon, Ambrose N; Kirui, Gilbert; Muasya, Daniel W; Mande, John D; Kariuki, Edward; Mijele, Dominic

2014-10-10

Regional anaesthetic techniques have been used in combination with systemic analgesics during small animal surgery to provide multimodal analgesia. Brachial plexus nerves block using local anaesthetics provides analgesia of the thoracic limb through desensitization of the nerves that provide sensory and motor innervation. This has been shown to reduce intra-operative anesthetic requirements and provide postoperative pain relief. Decreasing the doses of general anaesthetics allows more stable cardiopulmonary function during anaesthesia and the development of less side effects. The present case reports a successful use of brachial plexus blockade to supplement medetomidine-ketamine-isoflurane anaesthesia for repair of radio-ulna fracture in an adult cheetah (acinonyx jubatus). An adult male Cheetah weighing about 65 kg was presented with a history of leg carrying lameness of the left forelimb sustained following a car accident a week earlier. Clinical examination under general anaesthesia revealed slight dehydration and a swelling with a wound on the caudo-medial aspect of the left radio-ulna region. Crepitation was present on manipulation and radiography confirmed a complete transverse radio-ulna fracture of the left forelimb, which required open reduction and internal fixation. Brachial plexus blockade using lignocaine hydrochloride was used to supplement medetomidine-ketamine-isoflurane anaesthesia for the surgical procedure. Isoflurane anaesthesia was maintained at 0.5 - 2.0% throughout the surgical procedure, which was uneventful. Temperature and cardio-pulmonary parameters remained stable intra-operatively. Limb paralysis extended for 5 hours post-operatively, suggesting prolonged anaesthesia. To the researchers' knowledge, this is the first reported case of the use of brachial plexus blockade to supplement general anaesthesia to facilitate forelimb surgery in an adult cheetah. The use of brachial plexus block with a light plane of general anaesthesia proved to be successful. Brachial plexus block had a sparing effect on isoflurane anaesthesia as evidenced by the concentration used for maintenance of anaesthesia and the stability of the cardiopulmonary function. Moreover, absence of autonomic cardiopulmonary reactions to the surgical manipulation may be attributed to the efficacy of brachial plexus block. This anaesthesia protocol is therefore recommended for surgeries of the forelimb in wild cats.

Palpation- and ultrasound-guided brachial plexus blockade in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

da Cunha, Anderson F; Strain, George M; Rademacher, Nathalie; Schnellbacher, Rodney; Tully, Thomas N

2013-01-01

To compare palpation-guided with ultrasound-guided brachial plexus blockade in Hispaniolan Amazon parrots. Prospective randomized experimental trial. Eighteen adult Hispaniolan Amazon parrots (Amazona ventralis) weighing 252-295 g. After induction of anesthesia with isoflurane, parrots received an injection of lidocaine (2 mg kg(-1)) in a total volume of 0.3 mL at the axillary region. The birds were randomly assigned to equal groups using either palpation or ultrasound as a guide for the brachial plexus block. Nerve evoked muscle potentials (NEMP) were used to monitor effectiveness of brachial plexus block. The palpation-guided group received the local anesthetic at the space between the pectoral muscle, triceps, and supracoracoideus aticimus muscle, at the insertion of the tendons of the caudal coracobrachial muscle, and the caudal scapulohumeral muscle. For the ultrasound-guided group, the brachial plexus and the adjacent vessels were located with B-mode ultrasonography using a 7-15 MHz linear probe. After location, an 8-5 MHz convex transducer was used to guide injections. General anesthesia was discontinued 20 minutes after lidocaine injection and the birds recovered in a padded cage. Both techniques decreased the amplitude of NEMP. Statistically significant differences in NEMP amplitudes, were observed within the ultrasound-guided group at 5, 10, 15, and 20 minutes after injection and within the palpation-guided group at 10, 15, and 20 minutes after injection. There was no statistically significant difference between the two groups. No effect on motor function, muscle relaxation or wing droop was observed after brachial plexus block. The onset of the brachial plexus block tended to be faster when ultrasonography was used. Brachial plexus injection can be performed in Hispaniolan Amazon parrots and nerve evoked muscle potentials were useful to monitor the effects on nerve conduction in this avian species. Neither technique produced an effective block at the doses of lidocaine used and further study is necessary to develop a useful block for surgical analgesia. © Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Comparison Between Ultrasound-Guided Supraclavicular and Interscalene Brachial Plexus Blocks in Patients Undergoing Arthroscopic Shoulder Surgery: A Prospective, Randomized, Parallel Study.

PubMed

Ryu, Taeha; Kil, Byung Tae; Kim, Jong Hae

2015-10-01

Although supraclavicular brachial plexus block (SCBPB) was repopularized by the introduction of ultrasound, its usefulness in shoulder surgery has not been widely reported. The objective of this study was to compare motor and sensory blockades, the incidence of side effects, and intraoperative opioid analgesic requirements between SCBPB and interscalene brachial plexus block (ISBPB) in patients undergoing arthroscopic shoulder surgery. Patients were randomly assigned to 1 of 2 groups (ISBPB group: n = 47; SCBPB group: n = 46). The side effects of the brachial plexus block (Horner's syndrome, hoarseness, and subjective dyspnea), the sensory block score (graded from 0 [no cold sensation] to 100 [intact sensation] using an alcohol swab) for each of the 5 dermatomes (C5-C8 and T1), and the motor block score (graded from 0 [complete paralysis] to 6 [normal muscle force]) for muscle forces corresponding to the radial, ulnar, median, and musculocutaneous nerves were evaluated 20 min after the brachial plexus block. Fentanyl was administered in 50 μg increments when the patients complained of pain that was not relieved by the brachial plexus block. There were no conversions to general anesthesia due to a failed brachial plexus block. The sensory block scores for the C5 to C8 dermatomes were significantly lower in the ISBPB group. However, the percentage of patients who received fentanyl was comparable between the 2 groups (27.7% [ISBPB group] and 30.4% [SCBPB group], P = 0.77). SCBPB produced significantly lower motor block scores for the radial, ulnar, and median nerves than did ISBPB. A significantly higher incidence of Horner's syndrome was observed in the ISBPB group (59.6% [ISBPB group] and 19.6% [SCBPB group], P < 0.001). No patient complained of subjective dyspnea. Despite the weaker degree of sensory blockade provided by SCBPB in comparison to ISBPB, opioid analgesic requirements are similar during arthroscopic shoulder surgery under both brachial plexus blocks. However, SCBPB produces a better motor blockade and a lower incidence of Horner's syndrome than ISBPB.

Open Anterior Release of the Superior Transverse Scapular Ligament for Decompression of the Suprascapular Nerve During Brachial Plexus Surgery.

PubMed

Elzinga, Kate E; Curran, Matthew W T; Morhart, Michael J; Chan, K Ming; Olson, Jaret L

2016-07-01

Reconstruction of the suprascapular nerve (SSN) after brachial plexus injury often involves nerve grafting or a nerve transfer. To restore shoulder abduction and external rotation, a branch of the spinal accessory nerve is commonly transferred to the SSN. To allow reinnervation of the SSN, any potential compression points should be released to prevent a possible double crush syndrome. For that reason, the authors perform a release of the superior transverse scapular ligament at the suprascapular notch in all patients undergoing reconstruction of the upper trunk of the brachial plexus. Performing the release through a standard anterior open supraclavicular approach to the brachial plexus avoids the need for an additional posterior incision or arthroscopic procedure. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Outcome following nonoperative treatment of brachial plexus birth injuries.

PubMed

DiTaranto, Patricia; Campagna, Liliana; Price, Andrew E; Grossman, John A I

2004-02-01

Ninety-one infants who sustained a brachial plexus birth injury were treated with only physical and occupational therapy. The children were evaluated at 3-month intervals and followed for a minimum of 2 years. Sixty-three children with an upper or upper-middle plexus injury recovered good to excellent shoulder and hand function. In all of these children, critical marker muscles recovered M4 by 6 months of age. Twelve infants sustained a global palsy, with critical marker muscles remaining at M0-M1 at 6 months, resulting in a useless extremity. Sixteen infants with upper and upper-middle plexus injuries failed to recover greater than M1-M2 deltoid and biceps by 6 months, resulting in a very poor final outcome. These data provide useful guidelines for selection of infants for surgical reconstruction to improve ultimate outcome.

The results of supraclavicular brachial plexus neurolysis (without first rib resection) in management of post-traumatic "thoracic outlet syndrome".

PubMed

Dellon, A L

1993-01-01

This study evaluated the effectiveness of a supraclavicular brachial plexus neurolysis, without a first rib resection, in relieving the symptom complex traditionally termed "thoracic outlet syndrome." The hypothesis to be tested was that patients with a history of trauma may sustain stretch-type injury and subsequent scarring in and about the brachial plexus which is left untreated during transaxillary first rib resection. This prospective study included 14 patients who each had a neurolysis of the five roots and three trunks of the brachial plexus, plus an anterior scalenectomy through a supraclavicular approach. The results were determined on 11 patients with a mean follow-up of 26.4 months. The results of surgery were five excellent (45 percent), five good (45 percent) and one who failed to improve (10 percent). It is concluded that, with a history of trauma, the symptom complex commonly referred to as "thoracic outlet syndrome" may be primarily due to entrapment of the brachial plexus at sites proximal to the interval between the first rib and the clavicle. It is suggested that: 1) the term "brachial plexus compression" best describes the syndrome without directing the surgeon to remove any one specific anatomic structure and 2) the supraclavicular approach permits excellent surgical exposure of the compressed neurovascular structures. An unexpected observation was the formation of the lower trunk from C8 and T1 proximal to the first rib in the majority of these patients.

Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics

PubMed Central

Liu, Ying; Xu, Xun-cheng; Zou, Yi; Li, Su-rong; Zhang, Bin; Wang, Yue

2015-01-01

Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering ‘excellent’ and ‘good’ muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery. PMID:25883637

Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics.

PubMed

Liu, Ying; Xu, Xun-Cheng; Zou, Yi; Li, Su-Rong; Zhang, Bin; Wang, Yue

2015-02-01

Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering 'excellent' and 'good' muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery.

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

Brachial plexus assessment with three-dimensional isotropic resolution fast spin echo MRI: comparison with conventional MRI at 3.0 T

PubMed Central

Tagliafico, A; Succio, G; Neumaier, C E; Baio, G; Serafini, G; Ghidara, M; Calabrese, M; Martinoli, C

2012-01-01

Objective The purpose of our study was to determine whether a three-dimensional (3D) isotropic resolution fast spin echo sequence (FSE-cube) has similar image quality and diagnostic performance to a routine MRI protocol for brachial plexus evaluation in volunteers and symptomatic patients at 3.0 T. Institutional review board approval and written informed consent were guaranteed. Methods In this prospective study FSE-cube was added to the standard brachial plexus examination protocol in eight patients (mean age, 50.2 years) with brachial plexus pathologies and in six volunteers (mean age, 54 years). Nerve visibility, tissue contrast, edge sharpness, image blurring, motion artefact and acquisition time were calculated for FSE-cube sequences and for the standard protocol on a standardised five-point scale. The visibility of brachial plexus nerve and surrounding tissues at four levels (roots, interscalene area, costoclavicular space and axillary level) was assessed. Results Image quality and nerve visibility did not significantly differ between FSE-cube and the standard protocol (p>0.05). Acquisition time was statistically and clinically significantly shorter with FSE-cube (p<0.05). Pathological findings were seen equally well with FSE-cube and the standard protocol. Conclusion 3D FSE-cube provided similar image quality in a shorter acquisition time and enabled excellent visualisation of brachial plexus anatomy and pathology in any orientation, regardless of the original scanning plane. PMID:21343321

Biological plasticity in penguin heat-retention structures.

PubMed

Thomas, Daniel B; Fordyce, R Ewan

2012-02-01

Insulation and vascular heat-retention mechanisms allow penguins to forage for a prolonged time in water that is much cooler than core body temperature. Wing-based heat retention involves a plexus of humeral arteries and veins, which redirect heat to the body core rather than to the wing periphery. The humeral arterial plexus is described here for Eudyptes and Megadyptes, the only extant penguin genera for which wing vascular anatomy had not previously been reported. The erect-crested (Eudyptes sclateri) and yellow-eyed (Megadyptes antipodes) penguins both have a plexus of three humeral arteries on the ventral surface of the humerus. The wing vascular system shows little variation between erect-crested and yellow-eyed penguins, and is generally conserved across the six extant genera of penguins, with the exception of the humeral arterial plexus. The number of humeral arteries within the plexus demonstrates substantial variation and correlates well with wing surface area. Little penguins (Eudyptula minor) have two humeral arteries and a wing surface area of ∼ 75 cm(2) , whereas emperor penguins (Aptenodytes forsteri) have up to 15 humeral arteries and a wing surface area of ∼ 203 cm(2) . Further, the number of humeral arteries has a stronger correlation with wing surface area than with sea water temperature. We propose that thermoregulation has placed the humeral arterial plexus under a strong selection pressure, driving penguins with larger wing surface areas to compensate for heat loss by developing additional humeral arteries. Copyright © 2011 Wiley Periodicals, Inc.

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

PubMed Central

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; Howard, Daryl L.; Howland, John G.; Hackett, Mark J.

2016-01-01

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl−, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl− and Fe while K+ levels increase further from the ventricle as Cl− levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl− surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models. PMID:27351594

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE PAGES

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; ...

2016-06-28

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

[Physiology of the urethral sphincteric vesico-prostatic complex].

PubMed

Carmignani, L; Gadda, F; Dell'Orto, P; Ferruti, M; Grisotto, M; Rocco, F

2001-09-01

We propose a review of the literature about innervation and physiology of the urethral sphincteric complex. Parasympathetic innervation of the pelvic viscera comes from ventral branches of the sacral nerves (S2-S4). The orthosympathetic component derives from superior hypogastric plexus and runs down the hypogastric nerves to form the right and left pelvic plexus together with the parasympathetic component. The pelvic plexus is situated inferolaterally with respect to the rectum and runs on the surface of the levator ani muscle down to the prostatic apex. The pelvic plexus gives innervation to the rectum, the bladder, the prostate and the urethral sphincteric complex. The pelvic muscular floor is innervated by the somatic component (pudendal nerve) derived from the sacral branches (S2-S4). Bladder neck and smooth muscle urethral sphincter innervation is given mostly by the orthosympathetic component. The rhabdosphincter innervation comes from the pudendal nerve and from the pelvic plexus; its role in the continence mechanism is probably to give steady tonic urethral compression. Levator ani muscle takes part in the sphincteric complex with its anteromedial pubococcygeal portion. It plays its role strengthening the sphincteric tone during increase of the abdominal pressure or during active quick stop cessation of the urinary stream.

Characteristic features of hereditary neuropathy with liability to pressure palsy (HNPP) presenting with brachial plexopathy in soldiers.

PubMed

Kim, Kyoung-Eun

2014-11-15

A brachial plexus lesion is not common in hereditary neuropathy with liability to pressure palsy (HNPP). We report the clinical and electrodiagnostic features of young soldiers with HNPP presenting with brachial plexopathy. By reviewing 2year medical records from Korean military hospitals, we identified soldiers with brachial plexus lesions. Among them, patients diagnosed with HNPP were determined and clinical and electrophysiological findings were compared between HNPP and non-HNPP patients with a brachial plexus lesion. Thirteen patients (6.8%) were diagnosed with HNPP among 189 patients with a brachial plexus lesion. Push-ups, as either a punishment or an exercise, was the most frequent preceding event in HNPP patients (76.9%), whereas it was rare in non-HNPP patients. The distal motor latency of the median nerve showed the highest sensitivity (90.9%) and specificity (100%) for HNPP in patients with a brachial plexus lesion. In conclusion, HNPP should be suspected in patients with brachial plexopathy if brachial plexopathy develops after push-ups or if the distal motor latency of median nerves is prolonged. Copyright © 2014 Elsevier B.V. All rights reserved.

Brachial plexus injury management through upper extremity amputation with immediate postoperative prostheses.

PubMed

Malone, J M; Leal, J M; Underwood, J; Childers, S J

1982-02-01

Management of patients with brachial plexus injuries requires a team approach so that all aspects of their care are addressed simultaneously. This report examines elective amputation and prosthetic rehabilitation in a patient with brachial plexus avulsion of the left arm. The best possibility for good prosthetic rehabilitation is the early application of prosthetic devices with intensive occupational therapy. Using this type of approach, we have achieved significant improvement in amputation rehabilitation of upper extremity amputees treated with immediate postoperative conventional electric and myoelectric prostheses.

Characterization, solubilization and partial purification of serotonin 5-HT1C receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagaloff, K.A.

1986-01-01

/sup 125/I-Lysergic acid diethylamide (/sup 125/I-LSD) binds with high affinity to a unique serotonergic site on rat choroid plexus. These sites were localized to choroid plexus epithelial cells using a novel high resolution autoradiographic technique. In membrane preparations, the serotonergic site density was 3100 fmol/mg protein, which is 10 fold higher than the density of any other serotonergic site in brain homogenates. The pharmacology of this site, termed the 5-HT1c site, does not match that of 5-Ht1a, 5-HT1b or 5HT2 serotonergic sites. 5-Ht1c sites were solubilized from pig choroid plexus using the zwitterionic detergent, CHAPS. High affinity labelling of themore » solubilized site was obtained using the serotonergic radioligand, N1-methyl-2-(/sup 125/I)lysergic acid diethylamide (/sup 125/I-MIL). Choroid plexus tumors obtained from transgenic mice were examined for the presence of serotonin 5-HT1c receptors. /sup 125/I-LSD binding to choroid plexus tumors displays a pharmacological profile that matches the properties of 5-HT1c receptors in normal choroid plexus. The tumor exhibits the highest site density of serotonin receptors (6600 fmol/mg protein) found in any tissue. /sup 125/I-LSD autoradiography of brain sections from transgenic mice shows high levels of specific labelling over the tumor. The affinities of various indolealkyl, phenlakyl and beta-carboline derivatives for the serotonin 5-HT1c receptor were measured in pig choroid plexus using /sup 125/I-MIL. Serotonin precursors and metabolites were all very weak inhibitors of specific /sup 125/I-MIL binding. Structure-affinity relationships were determined for a number of indolealkylamine analogues. Only serotonin is present in cerebrospinal fluid at concentrations near its 5-HT1c inhibition constant, suggesting that serotonin is the natural 5-HT1c agonist.« less

Three-tesla magnetic resonance neurography of the brachial plexus in cervical radiculopathy.

PubMed

Yoshida, Takeshi; Sueyoshi, Takeshi; Suwazono, Shugo; Suehara, Masahito

2015-09-01

There have been no reports of the use of 3-Tesla magnetic resonance neurography (3T MRN) to characterize cervical radiculopathy. In particular, there are no reports of MRN of brachial plexus involvement in patients with cervical radiculopathy. We reviewed retrospectively 12 consecutive patients with cervical radiculopathy who underwent 3T MRN. The median age was 54.5 years. Eleven of 12 patients were men. The distribution of nerve-root signal abnormality was correlated with intervertebral foraminal stenosis and the presence of muscles that exhibited weakness and/or signs of denervation on electromyography. MRN abnormalities were found to extend into the distal part of the brachial plexus in 10 patients. This study demonstrates that MRN is potentially useful for diagnosis in patients with suspected cervical radiculopathy. Moreover, the finding of brachial plexus involvement on MRN may indicate a possible pathophysiological relationship between cervical radiculopathy and brachial plexopathy. © 2014 Wiley Periodicals, Inc.

Brachial Plexus Injury from CT-Guided RF Ablation Under General Anesthesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shankar, Sridhar, E-mail: shankars@ummhc.org; Sonnenberg, Eric van; Silverman, Stuart G.

2005-06-15

Brachial plexus injury in a patient under general anesthesia (GA) is not uncommon, despite careful positioning and, particularly, awareness of the possibility. The mechanism of injury is stretching and compression of the brachial plexus over a prolonged period. Positioning the patient within the computed tomography (CT) gantry for abdominal or chest procedures can simulate a surgical procedure, particularly when GA is used. The potential for brachial plexus injury is increased if the case is prolonged and the patient's arms are raised above the head to avoid CT image degradation from streak artifacts. We report a case of profound brachial plexusmore » palsy following a CT-guided radiofrequency ablation procedure under GA. Fortunately, the patient recovered completely. We emphasize the mechanism of injury and detail measures to combat this problem, such that radiologists are aware of this potentially serious complication.« less

Subscapularis slide correction of the shoulder internal rotation contracture after brachial plexus birth injury: technique and outcomes.

PubMed

Immerman, Igor; Valencia, Herbert; DiTaranto, Patricia; DelSole, Edward M; Glait, Sergio; Price, Andrew E; Grossman, John A I

2013-03-01

Internal rotation contracture is the most common shoulder deformity in patients with brachial plexus birth injury. The purpose of this investigation is to describe the indications, technique, and results of the subscapularis slide procedure. The technique involves the release of the subscapularis muscle origin off the scapula, with preservation of anterior shoulder structures. A standard postoperative protocol is used in all patients and includes a modified shoulder spica with the shoulder held in 60 degrees of external rotation and 30 degrees of abduction, aggressive occupational and physical therapy, and subsequent shoulder manipulation under anesthesia with botulinum toxin injections as needed. Seventy-one patients at 2 institutions treated with subscapularis slide between 1997 and 2010, with minimum follow-up of 39.2 months, were identified. Patients were divided into 5 groups based on the index procedure performed: subscapularis slide alone (group 1); subscapularis slide with a simultaneous microsurgical reconstruction (group 2); primary microsurgical brachial plexus reconstruction followed later by a subscapularis slide (group 3); primary microsurgical brachial plexus reconstruction followed later by a subscapularis slide combined with tendon transfers for shoulder external rotation (group 4); and subscapularis slide with simultaneous tendon transfers, with no prior brachial plexus surgery (group 5). Full passive external rotation equivalent to the contralateral side was achieved in the operating room in all cases. No cases resulted in anterior instability or internal rotation deficit. Internal rotation contracture of the shoulder after brachial plexus birth injury can be effectively managed with the technique of subscapularis slide.

The "waiting period" of sensory and motor axons in early chick hindlimb: its role in axon pathfinding and neuronal maturation.

PubMed

Wang, G; Scott, S A

2000-07-15

During embryonic development motor axons in the chick hindlimb grow out slightly before sensory axons and wait in the plexus region at the base of the limb for approximately 24 hr before invading the limb itself (Tosney and Landmesser, 1985a). We have investigated the role of this waiting period by asking, Is the arrest of growth cones in the plexus region a general property of both sensory and motor axons? Why do axons wait? Does eliminating the waiting period affect the further development of motor and sensory neurons? Here we show that sensory axons, like motor axons, pause in the plexus region and that neither sensory nor motor axons require cues from the other population to wait in or exit from the plexus region. By transplanting older or younger donor limbs to host embryos, we show that host axons innervate donor limbs on a schedule consistent with the age of the grafted limbs. Thus, axons wait in the plexus region for maturational changes to occur in the limb rather than in the neurons themselves. Both sensory and motor axons innervate their appropriate peripheral targets when the waiting period is eliminated by grafting older donor limbs. Therefore, axons do not require a prolonged period in the plexus region to sort out and project appropriately. Eliminating the waiting period does, however, accelerate the onset of naturally occurring cell death, but it does not enhance the development of central projections or the biochemical maturation of sensory neurons.

Angioarchitecture of the bovine spermatic cord.

PubMed

Polguj, Michał; Jȩdrzejewski, Kazimierz S; Topol, Mirosław

2011-04-01

We described the topography and morphometry of the testicular artery, pampiniform plexus veins, and indirect connections between them in the spermatic cord of the bull. Sixty microcorrosive casts of bovine spermatic cords were analyzed macroscopically, by stereomicroscopy, and by scanning electron microscopy. The average size of the testicles was 94.6 × 49.7 × 54.7 mm. The testicular artery formed a superiorly pointed cone-like structure with its base fixed to the proximal part of the gonad. The artery gave off one or two branches to the head of epididymis and to the deferens duct. The pampiniform plexus originated from intra-tunical veins. Veins of the pampiniform plexus were of smaller diameter but larger number than intra-tunical ones. The density of the veins of the pampiniform plexus was 9.37 ± 1.07 mm(-2) . The testicular vein began 90-121 mm above the superior pole of the testis. In 2.9% of specimens, the testicular vein was doubled. Numerous anastomoses among veins of pampiniform plexus were observed. Additionally, indirect anastomoses between the testicular artery and pampiniform plexus veins formed by the capillary network of the vasa vasorum of the testicular artery were visualized by scanning electron microscopy. In all cases, narrowings in the casts of the precapillary vessel were observed. We also documented the vasa vasorum of the testicular artery in bulls. The density of these vessels was 22.87 ± 11.48 mm(-2) . The indirect arteriovenous connections together with the presence of circular constrictions of the lumen in precapillary vessels may play a role in testicular blood flow regulation. Copyright © 2011 Wiley-Liss, Inc.

Choroid plexus glutathione peroxidases are instrumental in protecting the brain fluid environment from hydroperoxides during postnatal development.

PubMed

Saudrais, Elodie; Strazielle, Nathalie; Ghersi-Egea, Jean-Francois

2018-06-27

Hydrogen peroxide, released at low physiological concentration, is involved in different cell signaling pathways during brain development. When released at supraphysiological concentrations in brain fluids following an inflammatory, hypoxic or toxic stress, it can initiate lipid peroxidation, protein and nucleic acid damage and contribute to long-term neurological impairment associated with perinatal diseases. We found high glutathione peroxidase and glutathione reductase enzymatic activities in both lateral and fourth ventricle choroid plexus tissue isolated from developing rats, in comparison to the cerebral cortex and liver. Consistent with these, a high protein expression of glutathione peroxidases 1 and 4 was observed in choroid plexus epithelial cells, which form the blood-cerebrospinal fluid barrier. Live choroid plexuses isolated from newborn rats were highly efficient in detoxifying H2O2 from mock cerebrospinal fluid, illustrating the capacity of the choroid plexuses to control H2O2 concentration in the ventricular system of the brain. We used a differentiated cellular model of the blood-cerebrospinal fluid barrier coupled to kinetic and inhibition analyses to show that glutathione peroxidases are more potent than catalase to detoxify extracellular H2O2 at concentrations up to 250 µM. The choroidal cells also formed an enzymatic barrier preventing blood-borne hydroperoxides to reach the cerebrospinal fluid. These data point out the choroid plexuses as key structures in the control of hydroperoxide levels in the cerebral fluid environment during development, at a time when the protective glial cell network is still immature. Glutathione peroxidases are the main effectors of this choroidal hydroperoxide inactivation.

Peripheral Nerve Block as a Supplement to Light or Deep General Anesthesia in Elderly Patients Receiving Total Hip Arthroplasty: A Prospective Randomized Study.

PubMed

Mei, Bin; Zha, Hanning; Lu, Xiaolong; Cheng, Xinqi; Chen, Shishou; Liu, Xuesheng; Li, Yuanhai; Gu, Erwei

2017-12-01

Peripheral nerve block combined with general anesthesia is a preferable anesthesia method for elderly patients receiving hip arthroplasty. The depth of sedation may influence patient recovery. Therefore, we investigated the influence of peripheral nerve blockade and different intraoperative sedation levels on the short-term recovery of elderly patients receiving total hip arthroplasty. Patients aged 65 years and older undergoing total hip arthroplasty were randomized into 3 groups: a general anesthesia without lumbosacral plexus block group, and 2 general anesthesia plus lumbosacral plexus block groups, each with a different level of sedation (light or deep). The extubation time and intraoperative consumption of propofol, sufentanil, and vasoactive agent were recorded. Postoperative delirium and early postoperative cognitive dysfunction were assessed using the Confusion Assessment Method and Mini-Mental State Examination, respectively. Postoperative analgesia was assessed by the consumption of patient-controlled analgesics and visual analog scale scores. Discharge time and complications over a 30-day period were also recorded. Lumbosacral plexus block reduced opioid intake. With lumbosacral plexus block, intraoperative deep sedation was associated with greater intake of propofol and vasoactive agent. In contrast, patients with lumbosacral plexus block and intraoperative light sedation had lower incidences of postoperative delirium and postoperative cognitive decline, and earlier discharge readiness times. The 3 groups showed no difference in complications within 30 days of surgery. Lumbosacral plexus block reduced the need for opioids and offered satisfactory postoperative analgesia. It led to better postoperative outcomes in combination with intraoperative light sedation (high bispectral index).

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report.

PubMed

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-02-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block.

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report

PubMed Central

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-01-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block. PMID:29868459

Sup-ER orthosis: an innovative treatment for infants with birth related brachial plexus injury.

PubMed

Durlacher, Kim M; Bellows, Doria; Verchere, Cynthia

2014-01-01

Impairments in active and passive range of upper extremity supination and shoulder external rotation are common sequelae for children with delayed recovery from birth related brachial plexus injury. Orthotic intervention may complement traditional treatment strategies commonly employed in the newborn period. These authors describe their custom fabricated orthosis designed to balance shoulder growth and muscular function, and improve prognosis of long term functional outcomes for children with birth related brachial plexus injury. - Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Neurogenic Thoracic Outlet Syndrome Caused by Vascular Compression of the Brachial Plexus: A Report of Two Cases

PubMed Central

Hanna, Amgad; Bodden, Larry O'Neil; Siebiger, Gabriel R. L.

2018-01-01

Thoracic outlet syndrome (TOS) is caused by compression of the brachial plexus and/or subclavian vessels as they pass through the cervicothoracobrachial region, exiting the chest. There are three main types of TOS: neurogenic TOS, arterial TOS, and venous TOS. Neurogenic TOS accounts for approximately 95% of all cases, and it is usually caused by physical trauma (posttraumatic etiology), chronic repetitive motion (functional etiology), or bone or muscle anomalies (congenital etiology). We present two cases in which neurogenic TOS was elicited by vascular compression of the inferior portion of the brachial plexus. PMID:29497457

Plexus structure imaging with thin slab MR neurography: rotating frames, fly-throughs, and composite projections

NASA Astrophysics Data System (ADS)

Raphael, David T.; McIntee, Diane; Tsuruda, Jay S.; Colletti, Patrick; Tatevossian, Raymond; Frazier, James

2006-03-01

We explored multiple image processing approaches by which to display the segmented adult brachial plexus in a three-dimensional manner. Magnetic resonance neurography (MRN) 1.5-Tesla scans with STIR sequences, which preferentially highlight nerves, were performed in adult volunteers to generate high-resolution raw images. Using multiple software programs, the raw MRN images were then manipulated so as to achieve segmentation of plexus neurovascular structures, which were incorporated into three different visualization schemes: rotating upper thoracic girdle skeletal frames, dynamic fly-throughs parallel to the clavicle, and thin slab volume-rendered composite projections.

Perineural Spread of Nonmelanoma Skin Cancer to the Brachial Plexus: Identifying Anatomic Pathway(s).

PubMed

Marek, Tomas; Howe, B Matthew; Amrami, Kimberly K; Spinner, Robert J

2018-06-01

Perineural spread leading to brachial plexopathy has recently been described in cases of melanoma. The occurrence and mechanism for nonmelanoma skin cancer spread to the brachial plexus is poorly understood. A retrospective chart review of the Mayo Clinic database was conducted to identify patients with nonmelanoma skin cancer and brachial plexopathy between 2000 and 2017. Inclusion criteria were a history of nonmelanoma skin cancer, a clinical diagnosis of brachial plexopathy, imaging features of perineural spread, and a positive result of examination of a biopsy specimen showing tumor in a skin nerve. Thirty-seven patients with a history of nonmelanoma skin cancer and brachial plexopathy were identified. Inclusion criteria were fulfilled in 2 cases of cutaneous squamous cell carcinoma. One case of recurrent basal cell carcinoma with perineural spread confirmed in the brachial plexus by pathologic examination was excluded because confirmatory evidence of perineural spread from the skin to the brachial plexus was not available. Perineural spread of nonmelanoma skin cancer leading to brachial plexopathy is rare. Our 2 cases and the cases found in the literature demonstrate different entry points to the neural highway resulting in neurologic deficits. The cervical plexus serves as a hub for further spread in certain cases of perineural spread of skin cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Cost analysis of brachial plexus injuries: variability of compensation by insurance companies before and after surgery.

PubMed

Felici, N; Zaami, S; Ciancolini, G; Marinelli, E; Tagliente, D; Cannatà, C

2014-04-01

Traumatic paralysis of the brachial plexus is an extremely disabling pathology. The type of trauma most frequently suffered by this group of patients is due to motorcycle injuries. It therefore affects a population of young patients. In the majority of cases, these patients receive compensation for permanent damage from insurance companies. Surgery of the brachial plexus enables various forms of functional recovery, depending on the number of roots of the brachial plexus involved in the injury. The aim of this study is to compare the functional deficit and the extent of the related compensation before and after surgical intervention, and to evaluate the saving in economic terms (understood as the cost of compensation paid by insurance companies) obtainable through surgical intervention. The authors analysed the functional recovery obtained through surgery in 134 patients divided into 4 groups on the basis of the number of injured roots. The levels of compensation payable to the patient before surgical intervention, and 3 years after, were then compared. The results showed that the saving obtainable through surgical treatment of brachial plexus injuries may exceed 65% of the economic value of the compensation that would have been attributable to the same patients if they had not undergone surgical treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Intraoperative brachial plexus injury during emergence following movement with arms restrained: a preventable complication?

PubMed Central

Chandler, Mark H; DiMatteo, Laura; Hasenboehler, Erik A; Temple, Michael

2007-01-01

Background Despite considerable analysis and preventive strategies, brachial plexus injuries remain fairly common in the perioperative setting. These injuries range from brief periods of numbness or discomfort in the immediate postoperative period to, in rare cases, profound, prolonged losses of sensation and function. We present a case of an orthopedic surgery patient who suffered a brachial plexus injury while under anesthesia after trying to sit upright with his arms restrained. Case presentation After the uneventful placement of an intramedullary tibial nail, an 18 year old patient tried to sit upright with his arms restrained while still under the influence of anesthesia. In the immediate postoperative period, the patient complained of a profound loss of sensation in his left arm and an inability to flex his left elbow, suppinate his arm, or abduct and rotate his shoulder. Neurological examination and subsequent studies revealed a C5-6 brachial plexus injury. The patient underwent range of motion physical therapy and, over the next three months, regained the full function and sensation of his left arm. Conclusion Restraining arms during general anesthesia to prevent injury remains a wise practice. However, to avoid injuring the brachial plexus while the arms are restrained, extra caution must be used to prevent unexpected patient movement and to ensure gentle emergence. PMID:18271944

A novel technique for teaching the brachial plexus.

PubMed

Lefroy, Henrietta; Burdon-Bailey, Victoria; Bhangu, Aneel; Abrahams, Peter

2011-09-01

The brachial plexus has posed problems for both students and teachers throughout generations of medical education. The anatomy is intricate, and traditional pictorial representations can be difficult to understand and learn. Few innovative teaching methods have been reported. The basic anatomy of the brachial plexus is core knowledge required by medical students to aid clinical examination and diagnosis. A more detailed understanding is necessary for a variety of specialists, including surgeons, anaesthetists and radiologists. Here, we present a novel, cheap and interactive method of teaching the brachial plexus. Using coloured pipe cleaners, teachers and students can construct three-dimensional models using different colours to denote the origin and outflow of each nerve. The three-dimensional nature of the model also allows for a better understanding of certain intricacies of the plexus. Students may use these models as adjuncts for self study, didactic lectures and tutorials. Compared with traditional textbooks and whiteboards, the pipe-cleaner model was preferred by medical students, and provided a higher level of student satisfaction. This was demonstrated and analysed using student feedback forms. Our model could be incorporated into current curricula to provide an effective and enjoyable way of rapidly teaching a difficult concept. Other such novel methods for teaching complex anatomical principles should be encouraged and explored. © Blackwell Publishing Ltd 2011.

A cadaveric study to determine the minimum volume of methylene blue to completely color the nerves of brachial plexus in cats. An update in forelimb and shoulder surgeries.

PubMed

Mencalha, Rodrigo; Fernandes, Neide; Sousa, Carlos Augusto dos Santos; Abidu-Figueiredo, Marcelo

2014-06-01

To determine the minimum volume of methylene blue (MB) to completely color the brachial plexus (BP) nerves, simulating an effective anesthetic block in cats. Fifteen adult male cat cadavers were injected through subscapular approach with volumes of 2, 3, 4, 5 and 6 ml in both forelimbs, for a total of 30 brachial plexus blocks (BPB). After infusions, the specimens were carefully dissected preserving each nervous branch. The measurement of the effective area was indicated by the impregnation of MB. Nerves were divided into four segments from the origin at the spinal level until the insertion into the thoracic limb muscles. The blocks were considered effective only when all the nerves were strongly or totally colored. Volumes of 2, 3 and 4 ml were considered insufficient suggesting a failed block, however, volumes of 5 and 6 ml were associated with a successful block. The injection of methylene blue, in a volume of 6 ml, completely colored the brachial plexus. At volumes of 5 and 6 ml the brachial plexus blocks were considered a successful regional block, however, volumes of 2, 3 and 4 ml were considered a failed regional block.

Comparison between isotropic linear-elastic law and isotropic hyperelastic law in the finite element modeling of the brachial plexus.

PubMed

Perruisseau-Carrier, A; Bahlouli, N; Bierry, G; Vernet, P; Facca, S; Liverneaux, P

2017-12-01

Augmented reality could help the identification of nerve structures in brachial plexus surgery. The goal of this study was to determine which law of mechanical behavior was more adapted by comparing the results of Hooke's isotropic linear elastic law to those of Ogden's isotropic hyperelastic law, applied to a biomechanical model of the brachial plexus. A model of finite elements was created using the ABAQUS ® from a 3D model of the brachial plexus acquired by segmentation and meshing of MRI images at 0°, 45° and 135° of shoulder abduction of a healthy subject. The offset between the reconstructed model and the deformed model was evaluated quantitatively by the Hausdorff distance and qualitatively by the identification of 3 anatomical landmarks. In every case the Hausdorff distance was shorter with Ogden's law compared to Hooke's law. On a qualitative aspect, the model deformed by Ogden's law followed the concavity of the reconstructed model whereas the model deformed by Hooke's law remained convex. In conclusion, the results of this study demonstrate that the behavior of Ogden's isotropic hyperelastic mechanical model was more adapted to the modeling of the deformations of the brachial plexus. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Endothelin-converting enzyme-1 regulates trafficking and signalling of the neurokinin 1 receptor in endosomes of myenteric neurones

PubMed Central

Pelayo, Juan-Carlos; Poole, Daniel P; Steinhoff, Martin; Cottrell, Graeme S; Bunnett, Nigel W

2011-01-01

Abstract Neuropeptide signalling at the plasma membrane is terminated by neuropeptide degradation by cell-surface peptidases, and by β-arrestin-dependent receptor desensitization and endocytosis. However, receptors continue to signal from endosomes by β-arrestin-dependent processes, and endosomal sorting mediates recycling and resensitization of plasma membrane signalling. The mechanisms that control signalling and trafficking of receptors in endosomes are poorly defined. We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling substance P (SP) and the neurokinin 1 receptor (NK1R) in endosomes of myenteric neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and mouse intestine. SP (10 nm, 10 min) induced interaction of NK1R and β-arrestin at the plasma membrane, and the SP–NK1R–β-arrestin signalosome complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early endosomes, where ECE-1 can degrade SP. After 120 min, NK1R recycled from endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the vacuolar H+ATPase inhibitor bafilomycin A1, which prevent endosomal SP degradation, suppressed NK1R recycling by >50%. Preincubation of neurones with SP (10 nm, 5 min) desensitized Ca2+ transients to a second SP challenge after 10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK1R resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced activation of extracellular signal-regulated kinases, consistent with stabilization of the SP–NK1R–β-arrestin signalosome. By degrading SP and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK1R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating β-arrestin-mediated endosomal signalling. PMID:21878523

Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system

PubMed Central

Lieu, TinaMarie; Pelayo, Juan Carlos; Eriksson, Emily M.; Veldhuis, Nicholas A.; Bunnett, Nigel W.

2015-01-01

Activated G protein-coupled receptors traffic to endosomes and are sorted to recycling or degradative pathways. Endosomes are also a site of receptor signaling of sustained and pathophysiologically important processes, including inflammation. However, the mechanisms of endosomal sorting of receptors and the impact of disease on trafficking have not been fully defined. We examined the effects of inflammation on the subcellular distribution and trafficking of the substance P (SP) neurokinin 1 receptor (NK1R) in enteric neurons. We studied NK1R trafficking in enteric neurons of the mouse colon using immunofluorescence and confocal microscopy. The impact of inflammation was studied in IL10−/−-piroxicam and trinitrobenzenesulfonic acid colitis models. NK1R was localized to the plasma membrane of myenteric and submucosal neurons of the uninflamed colon. SP evoked NK1R endocytosis and recycling. Deletion of β-arrestin2, which associates with the activated NK1R, accelerated recycling. Inhibition of endothelin-converting enzyme-1 (ECE-1), which degrades endosomal SP, prevented recycling. Inflammation was associated with NK1R endocytosis in myenteric but not submucosal neurons. Whereas the NK1R in uninflamed neurons recycled within 60 min, NK1R recycling in inflamed neurons was delayed for >120 min, suggesting defective recycling machinery. Inflammation was associated with β-arrestin2 upregulation and ECE-1 downregulation, which may contribute to the defective NK1R recycling. We conclude that inflammation evokes redistribution of NK1R from the plasma membrane to endosomes of myenteric neurons through enhanced SP release and defective NK1R recycling. Defective recycling may be secondary to upregulation of β-arrestin2 and downregulation of ECE-1. Internalized NK1R may generate sustained proinflammatory signals that disrupt normal neuronal functions. PMID:26138465

Patient perceptions and recall of consent for regional anaesthesia compared with consent for surgery.

PubMed

Zarnegar, Roxaneh; Brown, Matthew R D; Henley, Matthew; Tidman, Victoria; Pathmanathan, Ahilan

2015-11-01

In Britain, consent for surgery is documented using a Department of Health form signed by the surgeon and the patient. In contrast, anaesthetic procedures have no formalised consent process. Evidence on the process of consent for regional anaesthesia, and patient perceptions of this, is scarce outside obstetric practice. We aimed to determine patient recall and perceptions of consent for interscalene brachial plexus block and compared this to surgical consent for shoulder arthroplasty. Prospective observational survey. A specialist musculoskeletal centre, UK. Forty-six patients (female:male 30:16, mean age 61 years) undergoing shoulder arthroplasty with interscalene brachial plexus block. Recall and understanding of consent for regional anaesthesia and surgery was examined using a semi-structured questionnaire 1-2 days after arthroplasty. Surgical consent forms and discussions recorded by the anaesthetist were examined in participants' medical notes to compare against the level of recall. Analysis to determine statistical significance was conducted using McNemar's test. Recall of surgical risks was overall significantly better than recall of brachial plexus block risks. Compared to their recollections of surgical risk, patients remembered fewer specific risks for brachial plexus block (p < 0.001). There were more patients unable to recall any risks when questioned about brachial plexus block than about their surgery (p < 0.05). One-third of patients did not regard the consent discussion about regional anaesthesia as important as consent for surgery and over one-quarter had not recognised the preoperative discussion about the brachial plexus block as a consent process similar to that conducted for surgery. Fundamental misunderstandings about the consent process are prevalent. Future work in this area should seek to investigate how documentation of the consent process and patients' understanding of consent for regional anaesthesia can be improved. © The Royal Society of Medicine.

Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium.

PubMed

Young, Robin K; Villalobos, Alice R A

2014-03-01

The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a "sink" for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl₂). At 50-1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [(3)H]choline. However, extended exposure to 250-500 nM cadmium increased [(3)H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase.

Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Hall, William H.; Li, Judy

2012-09-01

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median,more » 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.« less

Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium

PubMed Central

Young, Robin K.

2013-01-01

The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a “sink” for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl2). At 50–1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [3H]choline. However, extended exposure to 250–500 nM cadmium increased [3H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase. PMID:24401988

A Visual Description of the Dissection of the Cerebral Surface Vasculature and Associated Meninges and the Choroid Plexus from Rat Brain

PubMed Central

Bowyer, John F.; Thomas, Monzy; Patterson, Tucker A.; George, Nysia I.; Runnells, Jeffrey A.; Levi, Mark S.

2012-01-01

This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia 1,2. As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley3,4,5,6. The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function. PMID:23183685

A visual description of the dissection of the cerebral surface vasculature and associated meninges and the choroid plexus from rat brain.

PubMed

Bowyer, John F; Thomas, Monzy; Patterson, Tucker A; George, Nysia I; Runnells, Jeffrey A; Levi, Mark S

2012-11-14

This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia. As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley. The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function.

Investigation of brachial plexus traction lesions by peripheral and spinal somatosensory evoked potentials.

PubMed Central

Jones, S J

1979-01-01

Peripheral, spinal and cortical somatosensory evoked potentials were recorded in 26 patients with unilateral traction injuries of the brachial plexus ganglia. Of 10 cases explored surgically the recordings correctly anticipated the major site of the lesion in eight. PMID:422958

Neuro-Myelomatosis of the Brachial Plexus - An Unusual Site of Disease Visualized by FDG-PET/CT: A Case Report.

PubMed

Fukunaga, Hisanori; Mutoh, Tatsushi; Tatewaki, Yasuko; Shimomura, Hideo; Totsune, Tomoko; Terao, Chiaki; Miyazawa, Hidemitsu; Taki, Yasuyuki

2017-05-01

BACKGROUND Peripheral or cranial nerve root dysfunction secondary to invasion of the CNS in multiple myeloma is a rare clinical event that is frequently mistaken for other diagnoses. We describe the clinical utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scanning for diagnosing neuro-myelomatosis. CASE REPORT A 63-year-old woman whose chief complaints were right shoulder and upper extremity pain underwent MRI and 18F-FDG PET/CT scan. MRI revealed a non-specific brachial plexus tumor. 18F-FDG PET/CT demonstrated intense FDG uptake in multiple intramedullary lesions and in the adjacent right brachial plexus, indicating extramedullary neural involvement associated with multiple myeloma, which was confirmed later by a bone marrow biopsy. CONCLUSIONS This is the first reported case of neuro-myelomatosis of the brachial plexus. It highlights the utility of the 18F-FDG PET/CT scan as a valuable diagnostic modality.

Dysmorphic choroid plexuses and hydrocephalus associated with increased nuchal translucency: early ultrasound markers of de novo thanatophoric dysplasia type II with cloverleaf skull (Kleeblattschaedel).

PubMed

Tonni, Gabriele; Palmisano, Marcella; Ginocchi, Vladimiro; Ventura, Alessandro; Baldi, Maurizia; Baffico, Ave Maria

2014-11-01

Prenatal diagnosis of thanatophoric dysplasia (TD) type II presenting in the first trimester with increased nuchal translucency (NT) and cloverleaf skull (Kleeblattschaedel) have been scantly reported in the medical record. Abnormal choroid plexus has been seen in association with fetal anomalies. Here we described a case of increased NT associated with indented choroid plexuses, early onset hydrocephalus and cloverleaf skull in a fetus subsequently diagnosed at early second trimester to carry a de novo mutation encoding for TD type II. The findings of dysmorphic choroid plexus, early onset hydrocephalus and cloverleaf skull at first trimester scan may be early, useful ultrasound markers of TD type II. Molecular analysis to control for possible overlapping syndromes were performed and resulted negative. Postmortem X-ray and 3D-CT scan confirmed the cloverleaf skull, narrow thorax, straight femur with rhizomelic shortening of the limbs and the presence of a communicating hydrocephalus. © 2014 Japanese Teratology Society.

Bipolar Transfer of Latissimus Dorsi Myocutaneous Flap for Restoration of Elbow Flexion in Late Traumatic Brachial Plexus Injury: Evaluation of 13 Cases.

PubMed

Azab, Ahmed Abo-Hashem; Alsabbahi, Mohammad Salah

2017-02-01

Restoration of elbow flexion following traumatic brachial plexus injury represents a great challenge to the reconstructive surgeons. Functional muscle transfers come next to the sophisticated types of nerve surgery in this area. Many transfers are well known for restoration of elbow flexion; bipolar or unipolar latissimus dorsi, triceps brachii, sternocleidomastoid, pectoralis major, and Steindler flexorplasty. Evaluation of the outcome of bipolar transfer of latissimus dorsi myocutaneous flap when used to restore elbow flexion in late traumatic brachial plexus injury. Thirteen patients were included in this case series with careful evaluation both preoperatively and postoperatively both clinically and using electromyography. Almost 84.6% of patients (11 of 13) developed G3-4 on the Medical Research Council grading with relatively minimal both donor-site and recipient-site morbidity. Bipolar transfer of latissimus dorsi myocutaneous flap is a reliable method for restoration of elbow flexion in patients suffering from late sequelae of traumatic brachial plexus injury.

Trajectory of the main sensory and motor branches of the lumbar plexus outside the psoas muscle related to the lateral retroperitoneal transpsoas approach.

PubMed

Dakwar, Elias; Vale, Fernando L; Uribe, Juan S

2011-02-01

The minimally invasive lateral retroperitoneal transpsoas approach is increasingly used to treat various spinal disorders. Accessing the retroperitoneal space and traversing the abdominal wall poses a risk of injury to the major nervous structures and adds significant morbidity to the procedure. Most of the current literature focuses on the anatomy of the lumbar plexus within the substance of the psoas muscle. However, there is sparse knowledge regarding the trajectory of the lumbar plexus nerves that travel along the retroperitoneum and abdominal wall muscles in relation to the lateral approach to the spine. The objective of this study is to define the anatomical trajectories of the major motor and sensory branches of the lumbar plexus that are located outside the psoas muscle. Six adult fresh frozen cadaveric specimens were dissected and studied (12 sides). The relationship between the retroperitoneum, abdominal wall muscles, and the lumbar plexus nerves was analyzed in reference to the minimally invasive lateral retroperitoneal approach. Special attention was given to the lumbar plexus nerves that run outside of psoas muscle in the retroperitoneal cavity and within the abdominal muscle wall. The skin and muscles of the abdominal wall and the retroperitoneal cavity were dissected and analyzed with respect to the major motor and sensory branches of the lumbar plexus. The authors identified 4 nerves at risk during the lateral approach to the spine: subcostal, iliohypogastric, ilioinguinal, and lateral femoral cutaneous nerves. The anatomical trajectory of each of these nerves is described starting from the spinal column until their termination or exit from the pelvic cavity. There is risk of direct injury to the main motor/sensory nerves that supply the anterior abdominal muscles during the early stages of the lateral retroperitoneal transpsoas approach while obtaining access to the retroperitoneum. There is also a risk of injury to the ilioinguinal, iliohypogastric, and lateral femoral cutaneous nerves in the retroperitoneal space where they travel obliquely during the blunt retroperitoneal dissection. Moreover, there is a latent possibility of lesioning these nerves with the retractor blades against the anterior iliac crest.

Comparative study of phrenic nerve transfers with and without nerve graft for elbow flexion after global brachial plexus injury.

PubMed

Liu, Yuzhou; Lao, Jie; Gao, Kaiming; Gu, Yudong; Zhao, Xin

2014-01-01

Nerve transfer is a valuable surgical technique in peripheral nerve reconstruction, especially in brachial plexus injuries. Phrenic nerve transfer for elbow flexion was proved to be one of the optimal procedures in the treatment of brachial plexus injuries in the study of Gu et al. The aim of this study was to compare phrenic nerve transfers with and without nerve graft for elbow flexion after brachial plexus injury. A retrospective review of 33 patients treated with phrenic nerve transfer for elbow flexion in posttraumatic global root avulsion brachial plexus injury was carried out. All the 33 patients were confirmed to have global root avulsion brachial plexus injury by preoperative and intraoperative electromyography (EMG), physical examination and especially by intraoperative exploration. There were two types of phrenic nerve transfers: type1 - the phrenic nerve to anterolateral bundle of anterior division of upper trunk (14 patients); type 2 - the phrenic nerve via nerve graft to anterolateral bundle of musculocutaneous nerve (19 patients). Motor function and EMG evaluation were performed at least 3 years after surgery. The efficiency of motor function in type 1 was 86%, while it was 84% in type 2. The two groups were not statistically different in terms of Medical Research Council (MRC) grade (p=1.000) and EMG results (p=1.000). There were seven patients with more than 4 month's delay of surgery, among whom only three patients regained biceps power to M3 strength or above (43%). A total of 26 patients had reconstruction done within 4 months, among whom 25 patients recovered to M3 strength or above (96%). There was a statistically significant difference of motor function between the delay of surgery within 4 months and more than 4 months (p=0.008). Phrenic nerve transfers with and without nerve graft for elbow flexion after brachial plexus injury had no significant difference for biceps reinnervation according to MRC grading and EMG. A delay of the surgery after the 4 months might imply a bad prognosis for the recovery of the function. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sequential imaging of intraneural sciatic nerve endometriosis provides insight into symptoms of cyclical sciatica.

PubMed

Capek, Stepan; Amrami, Kimberly K; Howe, Benjamin M; Collins, Mark S; Sandroni, Paola; Cheville, John C; Spinner, Robert J

2016-03-01

Endometriosis of the nerve often remains an elusive diagnosis. We report the first case of intraneural lumbosacral plexus endometriosis with sequential imaging at different phases of the menstrual cycle: during the luteal phase and menstruation. Compared to the first examination, the examination performed during the patient's period revealed the lumbosacral plexus larger and hyperintense on T2-weighted imaging. The intraneural endometriosis cyst was also larger and showed recent hemorrhage. Additionally, this case represents another example of perineural spread of endometriosis from the uterus to the lumbosacral plexus along the autonomic nerves and then distally to the sciatic nerve and proximally to the spinal nerves.

Susceptibility of Primary Human Choroid Plexus Epithelial Cells and Meningeal Cells to Infection by JC Virus.

PubMed

O'Hara, Bethany A; Gee, Gretchen V; Atwood, Walter J; Haley, Sheila A

2018-04-15

JC polyomavirus (JCPyV) establishes a lifelong persistence in roughly half the human population worldwide. The cells and tissues that harbor persistent virus in vivo are not known, but renal tubules and other urogenital epithelial cells are likely candidates as virus is shed in the urine of healthy individuals. In an immunosuppressed host, JCPyV can become reactivated and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system. Recent observations indicate that JCPyV may productively interact with cells in the choroid plexus and leptomeninges. To further study JCPyV infection in these cells, primary human choroid plexus epithelial cells and meningeal cells were challenged with virus, and their susceptibility to infection was compared to the human glial cell line, SVG-A. We found that JCPyV productively infects both choroid plexus epithelial cells and meningeal cells in vitro Competition with the soluble receptor fragment LSTc reduced virus infection in these cells. Treatment of cells with neuraminidase also inhibited both viral infection and binding. Treatment with the serotonin receptor antagonist, ritanserin, reduced infection in SVG-A and meningeal cells. We also compared the ability of wild-type and sialic acid-binding mutant pseudoviruses to transduce these cells. Wild-type pseudovirus readily transduced all three cell types, but pseudoviruses harboring mutations in the sialic acid-binding pocket of the virus failed to transduce the cells. These data establish a novel role for choroid plexus and meninges in harboring virus that likely contributes not only to meningoencephalopathies but also to PML. IMPORTANCE JCPyV infects greater than half the human population worldwide and causes central nervous system disease in patients with weakened immune systems. Several recent reports have found JCPyV in the choroid plexus and leptomeninges of patients with encephalitis. Due to their role in forming the blood-cerebrospinal fluid barrier, the choroid plexus and leptomeninges are also poised to play roles in virus invasion of brain parenchyma, where infection of macroglial cells leads to the development of progressive multifocal leukoencephalopathy, a severely debilitating and often fatal infection. In this paper we show for the first time that primary choroid plexus epithelial cells and meningeal cells are infected by JCPyV, lending support to the association of JCPyV with meningoencephalopathies. These data also suggest that JCPyV could use these cells as reservoirs for the subsequent invasion of brain parenchyma. Copyright © 2018 American Society for Microbiology.

Collagen IX is required for the integrity of collagen II fibrils and the regulation of vascular plexus formation in Zebrafish caudal fins

PubMed Central

Huang, Cheng-chen; Wang, Tai-Chuan; Lin, Bo-Hung; Wang, Yi-Wen; Johnson, Stephen L.; Yu, John

2013-01-01

Capillary plexuses form during both vasculogenesis and angiogenesis and are remodeled into mature vessel types and patterns which are delicately orchestrated with the sizes and shapes of other tissues and organs. We isolated a zebrafish mutation named prp (for persistent plexus) that causes persistent formation of vascular plexuses in the caudal fins and consequent mispatterning of bony fin rays and the fin shape. Detailed analyses revealed that the prp mutation causes a significant reduction in the size and dramatic structural defects in collagen II-rich extracellular matrices called actinotrichia of both embryonic finfolds and adult fins. prp was mapped to chromosome 19 and found to encode the zebrafish collagen9α1 (col9α1) gene which is abundantly expressed in developing finfolds. A point mutation resulting in a leucine-to-histidine change was detected in the thrombospondin domain of the col9α1 gene in prp. Morpholino-mediated knockdown of col9α1 phenocopied the prp small-finfold phenotype in wild-type embryos, and an injection of plasmids containing the col9α1 cDNA into prp embryos locally restored the finfold size. Furthermore, we found that osteoblasts in prp mutants were mispatterned apparently following the abnormal vascular plexus pattern, demonstrating that blood vessels play an important role in the patterning of bony rays in zebrafish caudal fins. PMID:19501583

Collagen IX is required for the integrity of collagen II fibrils and the regulation of vascular plexus formation in zebrafish caudal fins.

PubMed

Huang, Cheng-chen; Wang, Tai-Chuan; Lin, Bo-Hung; Wang, Yi-Wen; Johnson, Stephen L; Yu, John

2009-08-15

Capillary plexuses form during both vasculogenesis and angiogenesis and are remodeled into mature vessel types and patterns which are delicately orchestrated with the sizes and shapes of other tissues and organs. We isolated a zebrafish mutation named prp (for persistent plexus) that causes persistent formation of vascular plexuses in the caudal fins and consequent mispatterning of bony fin rays and the fin shape. Detailed analyses revealed that the prp mutation causes a significant reduction in the size and dramatic structural defects in collagen II-rich extracellular matrices called actinotrichia of both embryonic finfolds and adult fins. prp was mapped to chromosome 19 and found to encode the zebrafish collagen9alpha1 (col9alpha1) gene which is abundantly expressed in developing finfolds. A point mutation resulting in a leucine-to-histidine change was detected in the thrombospondin domain of the col9alpha1 gene in prp. Morpholino-mediated knockdown of col9alpha1 phenocopied the prp small-finfold phenotype in wild-type embryos, and an injection of plasmids containing the col9alpha1 cDNA into prp embryos locally restored the finfold size. Furthermore, we found that osteoblasts in prp mutants were mispatterned apparently following the abnormal vascular plexus pattern, demonstrating that blood vessels play an important role in the patterning of bony rays in zebrafish caudal fins.

A comparative study of brachial plexus sonography and magnetic resonance imaging in chronic inflammatory demyelinating neuropathy and multifocal motor neuropathy.

PubMed

Goedee, H S; Jongbloed, B A; van Asseldonk, J-T H; Hendrikse, J; Vrancken, A F J E; Franssen, H; Nikolakopoulos, S; Visser, L H; van der Pol, W L; van den Berg, L H

2017-10-01

To compare the performance of neuroimaging techniques, i.e. high-resolution ultrasound (HRUS) and magnetic resonance imaging (MRI), when applied to the brachial plexus, as part of the diagnostic work-up of chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy (MMN). Fifty-one incident, treatment-naive patients with CIDP (n = 23) or MMN (n = 28) underwent imaging of the brachial plexus using (i) a standardized MRI protocol to assess enlargement or T2 hyperintensity and (ii) bilateral HRUS to determine the extent of nerve (root) enlargement. We found enlargement of the brachial plexus in 19/51 (37%) and T2 hyperintensity in 29/51 (57%) patients with MRI and enlargement in 37/51 (73%) patients with HRUS. Abnormal results were only found in 6/51 (12%) patients with MRI and 12/51 (24%) patients with HRUS. A combination of the two imaging techniques identified 42/51 (83%) patients. We found no association between age, disease duration or Medical Research Council sum-score and sonographic nerve size, MRI enlargement or presence of T2 hyperintensity. Brachial plexus sonography could complement MRI in the diagnostic work-up of patients with suspected CIDP and MMN. Our results indicate that combined imaging studies may add value to the current diagnostic consensus criteria for chronic inflammatory neuropathies. © 2017 EAN.

CAPILLARY NETWORK ALTERATIONS IN X-LINKED RETINOSCHISIS IMAGED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Romano, Francesco; Arrigo, Alessandro; Chʼng, Soon Wai; Battaglia Parodi, Maurizio; Manitto, Maria Pia; Martina, Elisabetta; Bandello, Francesco; Stanga, Paulo E

2018-06-05

To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp). After segmentation and quality review, optical coherence tomography angiography slabs were imported into ImageJ 1.50 (NIH; Bethesda) and digitally binarized. Quantification of vessel density was performed after foveal avascular zone area measurement and exclusion. Patients were additionally divided into "responders" and "nonresponders" to dorzolamide therapy. Foveal avascular zone area resulted markedly enlarged at the deep capillary plexus (P < 0.001), particularly in nonresponders. Moreover, patients disclosed a significant deep capillary plexus rarefaction, when compared with controls (P: 0.04); however, a subanalysis revealed that this damage was limited to the fovea (P: 0.006). Finally, the enlargement of foveal avascular zone area positively correlated with a decline in best-corrected visual acuity (P: 0.01). Prominent foveal vascular impairment is detectable in the deep capillary plexus of patients with X-linked retinoschisis. Our results correlate with functional outcomes, suggesting a possible vascular role in X-linked retinoschisis clinical manifestations.

Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

PubMed

da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

2017-06-01

The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

Current Concept in Adult Peripheral Nerve and Brachial Plexus Surgery.

PubMed

Rasulic, Lukas

2017-01-01

Peripheral nerve injuries and brachial plexus injuries are relatively frequent. Significance of these injuries lies in the fact that the majority of patients with these types of injuries constitute working population. Since these injuries may create disability, they present substantial socioeconomic problem nowadays. This article will present current state-of-the-art achievements of minimal invasive brachial plexus and peripheral nerve surgery. It is considered that the age of the patient, the mechanism of the injury, and the associated vascular and soft-tissue injuries are factors that primarily influence the extent of recovery of the injured nerve. The majority of patients are treated using classical open surgical approach. However, new minimally invasive open and endoscopic approaches are being developed in recent years-endoscopic carpal and cubital tunnel release, targeted minimally invasive approaches in brachial plexus surgery, endoscopic single-incision sural nerve harvesting, and there were even attempts to perform endoscopic brachial plexus surgery. The use of the commercially available nerve conduits for bridging short nerve gap has shown promising results. Multidisciplinary approach individually designed for every patient is of the utmost importance for the successful treatment of these injuries. In the future, integration of biology and nanotechnology may fabricate a new generation of nerve conduits that will allow nerve regeneration over longer nerve gaps and start new chapter in peripheral nerve surgery.

Macrophages and dendritic cells in the rat meninges and choroid plexus: three-dimensional localisation by environmental scanning electron microscopy and confocal microscopy.

PubMed

McMenamin, Paul G; Wealthall, Rosamund J; Deverall, Marie; Cooper, Stephanie J; Griffin, Brendan

2003-09-01

The present investigation provides novel information on the topographical distribution of macrophages and dendritic cells (DCs) in normal meninges and choroid plexus of the rat central nervous system (CNS). Whole-mounts of meninges and choroid plexus of Lewis rats were incubated with various anti-leucocyte monoclonal antibodies and either visualised with gold-conjugated secondary antibody followed by silver enhancement and subsequent examination by environmental scanning electron microscopy or by the use of fluorochromes and confocal microscopy. Large numbers of MHC class II(+) putative DCs were identified on the internal or subarachnoid aspect of dural whole-mounts, on the surface of the cortex (pia/arachnoid) and on the surface of the choroid plexus. Occupation of these sites would allow DCs access to cerebrospinal fluid (CSF) and therefore allow antigens into the subarachnoid space and ventricles. By contrast, macrophages were less evident at sites exposed to CSF and were more frequently located within the connective tissue of the dura/arachnoid and choroid plexus stroma and also in a sub-pial location. The present data suggest that DC may be strategically located within the CNS to sample CSF-borne antigens. Furthermore, the data suggest that CNS tissue samples collected without careful removal of the meninges may inadvertently be contaminated by DCs and meningeal macrophages.

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

PubMed Central

Bankaitis, Eric D.; Bechard, Matthew E.; Wright, Christopher V.E.

2015-01-01

In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the “trunk epithelium.” Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial “plexus state,” which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium. PMID:26494792

Axillary Brachial Plexus Blockade for the Reflex Sympathetic Dystrophy Syndrome.

ERIC Educational Resources Information Center

Ribbers, G. M.; Geurts, A. C. H.; Rijken, R. A. J.; Kerkkamp, H. E. M.

1997-01-01

Reflex sympathetic dystrophy syndrome (RSD) is a neurogenic pain syndrome characterized by pain, vasomotor and dystrophic changes, and often motor impairments. This study evaluated the effectiveness of brachial plexus blockade with local anaesthetic drugs as a treatment for this condition. Three patients responded well; three did not. (DB)

IRRITANT AGONISTS AND AIR POLLUTANTS: NEUROLOGICALLY MEDIATED RESPIRATORY AND CARDIOVASCULAR RESPONSES

EPA Science Inventory

Situated within and just beneath the airway epithelium is a dense plexus of sensory nerves. These sensory (afferent) nerves serve as sentinels at the gateway between the organism and the inhaled air. This airway mucosal nerve plexus is present from the nose to the most peripheral...

Effects of Botulinum Toxin on Reducing the Co-contraction of Antagonists in Birth Brachial Plexus Palsy

PubMed Central

Shin, Yong Beom; Chang, Jae Hyeok; Cha, Young Sun; Ko, Hyun-Yoon

2014-01-01

Birth brachial plexus palsy (BBPP) is usually caused by plexus traction during difficult delivery. Although the possibility of complete recovery is relatively high, 5% to 25% of BBPP cases result in prolonged and persistent disability. In particular, muscle imbalance and co-contraction around the shoulder and elbow cause abnormal motor performance, osseous deformities, and joint contracture. Physical and occupational therapies have most commonly been used, but these conventional therapeutic strategies have often been inadequate, in managing the residual muscle imbalance and muscle co-contraction. Therefore, we attempted to improve the functional movements, by using botulinum toxin type A, to reduce the abnormal co-contraction of the antagonist muscles. PMID:24639937

A Review of Brachial Plexus Birth Palsy: Injury and Rehabilitation.

PubMed

Raducha, Jeremy E; Cohen, Brian; Blood, Travis; Katarincic, Julia

2017-11-01

Brachial plexus injuries during the birthing process can leave infants with upper extremity deficits corresponding to the location of the lesion within the complex plexus anatomy. Manifestations can range from mild injuries with complete resolution to severe and permanent disability. Overall, patients have a high rate of spontaneous recovery (66-92%).1,2 Initially, all lesions are managed with passive range motion and observation. Prevention and/or correction of contractures with occupational therapy and serial splinting/casting along with encouraging normal development are the main goals of non-operative treatment. Surgical intervention may be war- ranted, depending on functional recovery. [Full article available at http://rimed.org/rimedicaljournal-2017-11.asp].

A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

PubMed Central

Lindeman, Geoffrey J.; Dagnino, Lina; Gaubatz, Stefan; Xu, Yuhui; Bronson, Roderick T.; Warren, Henry B.; Livingston, David M.

1998-01-01

Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. PMID:9553039

[Brachial plexus. Anesthesia and analgesia].

PubMed

Schulz-Stübner, S

2003-07-01

This review explains the different approaches to the brachial plexus (posterior cervical, interscalene, supra- and infraclavicular, and axillary) and their advantages and disadvantages (indications, contraindications, and complications) for surgery and postoperative or chronic pain management. One of the focussed areas of this review is the use of continuous catheter techniques. Information about the most commonly used local anesthetics as well as adjuncts suggested in the literature is summarized. As essential components for the success of those techniques, organizational and documentation requirements are described. In summary, regional techniques for single shot or continuous block of the brachial plexus are an efficient and safe way of providing anesthesia and analgesia for surgery or pain in the region of the shoulder, arm, or hand.

Celiac Plexus Block as a Predictor of Surgical Outcome for Sympathetically Mediated Abdominal Pain in a Case of Suspected Median Arcuate Ligament Syndrome: A Case Report.

PubMed

Sun, Zhuo; Fritz, David A; Turner, Suzanne; Hardy, David M; Meiler, Steffen E; Martin, Dan C; Dua, Anterpreet

2018-02-14

Median arcuate ligament syndrome (MALS), also known as celiac artery compression syndrome, is an uncommon condition classically characterized by chronic abdominal pain, weight loss, and abdominal bruit. Chronic mesenteric ischemia caused by intermittent compression of the celiac artery by the MAL provokes upper abdominal pain that is sympathetically mediated via the celiac plexus. Because it is a diagnosis of exclusion, diagnosis of MALS in the clinical setting is typically challenging. We present an atypical case which highlights the utility of celiac plexus block as both an assistant diagnostic tool and a predictor of surgical outcomes for suspected MALS.

Unique Phrenic Nerve-Sparing Regional Anesthetic Technique for Pain Management after Shoulder Surgery

PubMed Central

Olsen, David A.; Amundson, Adam W.

2017-01-01

Background Ipsilateral phrenic nerve blockade is a common adverse event after an interscalene brachial plexus block, which can result in respiratory deterioration in patients with preexisting pulmonary conditions. Diaphragm-sparing nerve block techniques are continuing to evolve, with the intention of providing satisfactory postoperative analgesia while minimizing hemidiaphragmatic paralysis after shoulder surgery. Case Report We report the successful application of a combined ultrasound-guided infraclavicular brachial plexus block and suprascapular nerve block in a patient with a complicated pulmonary history undergoing a total shoulder replacement. Conclusion This case report briefly reviews the important innervations to the shoulder joint and examines the utility of the infraclavicular brachial plexus block for postoperative pain management. PMID:29410922

[Osseontegration of trial implants of carbon fiber reinforced plastics].

PubMed

Schreiner, U; Schwarz, M; Scheller, G; Schroeder-Boersch, H; Jani, L

2000-01-01

To what extent are carbon fibre-reinforced plastics (CFRP) suitable as an osseous integration surface for implants? CFRP test implants having a plexus-structured, rhombus-structured, and plexus-structured, hydroxyapatite surface were implanted in the femura of mini-plgs. Exposure time lasted 12 weeks. The implants were subjected to a macroradiological, a histological-histomorphometrical, and a fluorescence-microscopical evaluation. One half of the uncoated, plexus-structured implants were not osteointegrated, the other half displayed an osteointegration rate of 11.8% in the spongy area and 29.8% in the cortex layer. The HA-coated test implants showed an osteointegration of 29.5% in the spongiosa and 56.8% in the cortex layer. The rhombus-structured test implants had an osteointegration of 29.2% (spongiosa) and 46.2% (cortex layer). Compared to the osteointegration of metallic, especially titanium surfaces the CFRP surfaces tested by us fared worse, especially the uncoated, plexus-structured surfaces. For this reason we view very critically the use of carbon-fibre reinforced plastics together with the surfaces tested by us as osteointegrating surfaces.

Effects of cafeteria diet on the jejunum in sedentary and physically trained rats.

PubMed

Scoaris, Célia Regina; Rizo, Gabriela Vasconcelos; Roldi, Luciana Patrícia; de Moraes, Solange Marta Franzói; de Proença, André Ricardo Gomes; Peralta, Rosane Marina; Natali, Maria Raquel Marçal

2010-03-01

The effects of a cafeteria diet on the small intestine were investigated in adult Wistar rats under sedentary conditions and after physical training. Parameters including morphometry, enzyme activities, and total myenteric populations in the jejunum were evaluated. The cafeteria diet, characterized as hyperlipidic, produced obese rats, corroborated by increases in the Lee index and the weights of the periepididymal and retroperitoneal adipose tissues (P<0.01). Obesity caused increases in the length of the small intestine, villi height, crypt depth, whole-wall thickness (P<0.05), and the enzymatic activities of alkaline phosphatase, lipase, and sucrase (P<0.01), in addition to a reduction in the number of goblet cells (P<0.05). With reference to the jejunal intrinsic innervations, the total number and area of myenteric neurons was unchanged regardless of the group. Physical training promoted 1) a reduction of the weight in the retroperitoneal and periepididymal adipose tissues (P<0.05) and 2) an increase in the thickness of the muscular layer (P<0.05). The cafeteria diet promoted obesity in rodents, leading to alterations in morphometry and enzymatic intestinal parameters, which were partily attenuated by physical training. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Addition of dexmedetomidine to bupivacaine in supraclavicular brachial plexus block.

PubMed

Aksu, Recep; Bicer, Cihangir

2017-06-26

Research is ongoing to determine the lowest dose of local anesthetics in brachial plexus block that provides adequate anesthesia and postoperative analgesia and reduces complications related to local anesthetics. Patients 18-65 years of age who underwent upper limb surgery and who received ultrasound-guided supraclavicular brachial plexus block at the Erciyes University Faculty of Medicine Hospital between February 2014 and January 2015 were included in the study (n=50). Supraclavicular brachial plexus blocks were performed on Group B cases by adding 30 ml 0.33% bupivacaine and on Group BD cases by adding 15 ml 0.33% bupivacaine and 1 µg / kg dexmedetomidine. Block success was evaluated by the onset and block duration of motor and sensory block and the duration of analgesia. The block success of Group B and Group BD was 92.6% and 89.3%, respectively (P = 1.000). Onset time of sensory block, degree of sensory block, duration of sensory block, onset time of motor block, degree of motor block and duration of motor block were similar in both groups in the intergroup comparison (P > 0.05). Duration of analgesia and the operative conditions of groups were similar (P > 0.05). In the implementation of ultrasound-guided supraclavicular brachial plexus block, block success, sensory and motor block and analgesia duration were similar for patients anaesthetized with 30 ml of bupivacaine in comparison with dexmedetomidine+bupivacaine (when the bupivacaine dose was reduced by 50% by the addition of the adjuvant).

Prevalence of Neuropathic Pain in Patients with Traumatic Brachial Plexus Injury: A Multicenter Prospective Hospital-Based Study.

PubMed

Ciaramitaro, Palma; Padua, Luca; Devigili, Grazia; Rota, Eugenia; Tamburin, Stefano; Eleopra, Roberto; Cruccu, Giorgio; Truini, Andrea

2017-12-01

Prevalence and clinical characteristics of neuropathic pain due to traumatic brachial plexus injury. Observational epidemiological study. Hospital-based multicenter study. One hundred seven prospectively enrolled patients with brachial plexus injury. All the patients underwent clinical examination and neurophysiological testing for a definitive diagnosis of the brachial plexus lesion. The DN4 questionnaire was used to identify neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to evaluate the different symptoms of neuropathic pain. The SF36 questionnaire and the Beck Depression Inventory (BDI) were used to assess quality of life and mood disturbances in patients with neuropathic pain. Of the 107 enrolled patients, 74 had pain (69%); neuropathic pain, as assessed by means of the DN4, was identified in 60 (56%) of these patients. According to the NPSI, the most frequent and severe pain type was the spontaneous burning pain. Clinical and neurophysiological findings showed that pain is unrelated to age but is associated with the severity of peripheral nerve damage. The SF36 questionnaire and BDI showed that neuropathic pain impairs quality of life and causes depression. Our study provides information on the prevalence, characteristics, and variables associated with neuropathic pain due to traumatic brachial plexus injuries that might provide a basis for improving the clinical management of this condition. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum. Presence of a single cilium

PubMed Central

Junquera, Concepción; Martínez-Ciriano, Carmen; Castiella, Tomás; Serrano, Pedro; Azanza, María Jesús; Ramón y Cajal Junquera, Santiago

2007-01-01

Abstract Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duo-denum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia. They present triangular or spindle forms and a very voluminous nucleus with scarce per-inuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular con-tacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells. We also observe a population of interstitial cells of stellate morphology in the connective tissue that sur-rounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium show-ing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining c-kit, CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single cilium. Some populations of ICCs in the rabbit duodenum present certain immunohistochemical and ultrastructural characteristics that often are present in progenitor cells. PMID:17760839

Unilateral cervical plexus block for prosthetic laryngoplasty in the standing horse.

PubMed

Campoy, L; Morris, T B; Ducharme, N G; Gleed, R D; Martin-Flores, M

2018-04-20

Locoregional anaesthetic techniques can facilitate certain surgeries being performed under standing procedural sedation. The second and third spinal cervical nerves (C2, C3) are part of the cervical plexus and provide sensory innervation to the peri-laryngeal structures in people; block of these nerves might permit laryngeal lateralisation surgery in horses. To describe the anatomical basis for an ultrasound-guided cervical plexus block in horses. To compare this block with conventional local anaesthetic tissue infiltration in horses undergoing standing prosthetic laryngoplasty. Cadaveric study followed by a double-blinded prospective clinical trial. A fresh equine cadaver was dissected to characterise the distribution of C2 and C3 to the perilaryngeal structures on the left side. A second cadaver was utilised to correlate ultrasound images with the previously identified structures; a tissue marker was injected to confirm the feasibility of an ultrasound-guided approach to the cervical plexus. In the clinical study, horses were assigned to two groups, CP (n = 17; cervical plexus block) and INF (n = 17; conventional tissue infiltration). Data collection and analyses included time to completion of surgical procedure, sedation time, surgical field conditions and surgeon's perception of block quality. We confirmed that C2 and C3 provided innervation to the perilaryngeal structures. The nerve root of C2 was identified ultrasonographically located between the longus capitis and the cleidomastoideus muscles, caudal to the parotid gland. The CP group was deemed to provide better (P<0.0002) surgical conditions with no differences in the other variables measured. Further studies with larger numbers of horses may be necessary to detect smaller differences in surgical procedure completion time based on the improved surgical filed conditions. For standing unilateral laryngeal surgery, a cervical plexus block is a viable alternative to tissue infiltration and it improves the surgical field conditions. © 2018 EVJ Ltd.

Refinement of myotome values in the upper limb: Evidence from brachial plexus injuries.

PubMed

Bell, S W; Brown, M J C; Hems, T J

2017-02-01

We reviewed patients with partial supraclavicular brachial plexus injuries in order to refine the myotome values of the upper limb. Forty-two patients with defined partial injuries to the supraclavicular brachial plexus were reviewed from a prospective database. The injuries patterns covered C5, C5-6, C5-7, C5-8, C7-T1 and C8-T1 roots. Upper plexus injuries were classified on the basis of surgical exploration and intraoperative stimulation and lower plexus injuries from MRI. Flexor Carpi Radialis (FCR) was paralyzed in C5-7 injuries, in addition to paralysis of deltoid, supraspinatus, infraspinatus and biceps, when compared to C5-6 injuries. Complete paralysis of Flexor Digitorum Profundus (FDP) and Flexor Digitorum Superficialis (FDS) to all digits was identified in C7-T1 injuries. In C5-8 injuries weakness was noted in FDP of ulnar digits and intrinsics innervated by the ulnar nerve, while in C8-T1 injuries paralysis was noted in the FDP to the radial digits. All patients with C8-T1 injuries had paralysis of FDS and the thenar muscles. In upper plexus injuries paralysis of FCR indicated involvement of C7 root in addition to C5 and C6 roots. The results provide new detail of innervation of muscles acting on the hand. Flexor muscles and intrinsic muscles of the thumb and radial fingers (median nerve) have an important contribution from T1, while for those acting on the ulnar digits (ulnar nerve) the main contribution is from C8 with some input from C7. T1 also gives consistent innervation to extensor pollicis longus. A revised myotome chart for the upper limb is proposed. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Lycopene mitigates β-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer's disease rats.

PubMed

Liu, Chong-Bin; Wang, Rui; Yi, Yan-Feng; Gao, Zhen; Chen, Yi-Zhu

2018-03-01

The choroid plexus is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, whether lycopene is involved in inflammatory responses at the choroid plexus in the early stages of Alzheimer's disease, and its molecular underpinnings are elusive. In this rat study, lycopene was used to investigate its protective effects on inflammation caused by β-amyloid. We characterized the learning and memory abilities, cytokine profiles of circulating TNF-α, IL-1β and IL-6β in the serum and the expressions of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein at the choroid plexus. The results showed that functional deficits of learning and memory in lycopene treatment groups were significantly improved compared to the control group without lycopene treatment in water maze test. The levels of serum TNF-α, IL-1β and IL-6β were significantly increased, and the expressions of TLR4 and NF-κB p65 mRNA and protein at the choroid plexus were up-regulated, indicating inflammation response was initiated following administration of Aβ 1-42 . After intragastric pretreatment with lycopene, inflammatory cytokines were significantly reduced and lycopene also reversed the Aβ 1-42 induced up-regulation of TLR4 and NF-κB p65 mRNA and protein expressions at the choroid plexus. These results provided a novel evidence that lycopene significantly improved cognitive deficits and were accompanied by the attenuation of inflammatory injury via blocking the activation of NF-κB p65 and TLR4 expressions and production of cytokines, thereby endorsing its usefulness for diminishing β-amyloid deposition in the hippocampus tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence Suggesting that the Buccal and Zygomatic Branches of the Facial Nerve May Contain Parasympathetic Secretomotor Fibers to the Parotid Gland by Means of Communications from the Auriculotemporal Nerve.

PubMed

Tansatit, Tanvaa; Apinuntrum, Prawit; Phetudom, Thavorn

2015-12-01

The auriculotemporal nerve is one of the peripheral nerves that communicates with the facial nerve. However, the function of these communications is poorly understood. Details of how these communications form and connect with each other are still unclear. In addition, a reliable anatomical landmark for locating these communications during surgery has not been sufficiently described. Microdissection was performed on 20 lateral hemifaces of 10 soft-embalmed cadavers to investigate facial-auriculotemporal nerve communications with emphasis on determining their function. The auriculotemporal nerve was identified in the retromandibular space and traced towards its terminations. The communicating branches were followed and the anatomical relationships to surrounding structures observed. The auriculotemporal nerve is suspended above the maxillary artery in the dense retromandibular fascia behind the mandibular ramus. It forms a knot and fans out, providing multiple branches in all directions in the sagittal plane. Inferiorly, it connects the maxillary periarterial plexus, while minute branches supply the temporomandibular joint anteriorly. The larger branches mainly communicate with the branches of the temporofacial division of the facial nerve, and the auricular branches enter the fascia of the auricular cartilage posteriorly. The temporal branches and occasionally the zygomatic branches arise superiorly to distribute within the temporoparietal fascia. The auriculotemporal nerve forms the parotid retromandibular plexus through two types of communication. It sends one to three branches to join the zygomatic and buccal branches of the facial nerve at the branching area of the temporofacial division. It also communicates with the periarterial plexus of the superficial temporal and maxillary arteries. This plexus continues anteriorly along the branches of the facial nerve and the periarterial plexus of the transverse facial artery as the parotid periductal autonomic plexus, supplying the branches of the parotid duct within the loop of the two main divisions of the parotid gland. A single cutaneous zygomatic branch arising from the auriculotemporal nerve in some specimens, the intraparotid communications with the zygomatic and the buccal trunks of the facial nerve, the retromandibular communications with the superficial temporal-maxillary periarterial plexuses, and the periductal autonomic plexus between the loop of the two main facial divisions lead to the suggestion that these communications of the auriculotemporal nerve convey the secretomotor to the zygomatic and buccal branches of the facial nerve. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effectiveness of primary conservative management for infants with obstetric brachial plexus palsy.

PubMed

Bialocerkowski, Andrea; Kurlowicz, Kirsty; Vladusic, Sharon; Grimmer, Karen

Obstetric brachial plexus palsy, a complication of childbirth, occurs in 1-3 per 1000 live births internationally. Traction and/or compression of the brachial plexus is thought to be the primary mechanism of injury and this may occur in utero, during the descent through the birth canal or during delivery. This results in a spectrum of injuries that vary in severity, extent of damage and functional use of the affected upper limb. Most infants receive treatment, such as conservative management (physiotherapy, occupational therapy) or surgery; however, there is controversy regarding the most appropriate form of management. To date, no synthesised evidence is available regarding the effectiveness of primary conservative management for obstetric brachial plexus palsy. The objective of this review was to systematically assess the literature and present the best available evidence that investigated the effectiveness of primary conservative management for infants with obstetric brachial plexus palsy. A systematic literature search was performed using 14 databases: TRIP, MEDLINE, CINAHL, AMED, Web of Science, Proquest 5000, Evidence Based Medicine Reviews, Expanded Academic ASAP, Meditext, Science Direct, Physiotherapy Evidence Database, Proquest Digital Dissertations, Open Archives Initiative Search Engine, Australian Digital Thesis Program. Those studies that were reported in English and published over the last decade (July 1992 to June 2003) were included in this review. Quantitative studies that investigated the effectiveness of primary conservative management for infants with obstetric brachial plexus palsy were eligible for inclusion in this review. This excluded studies that solely investigated the effect of primary surgery for these infants, management of secondary deformities and the investigation of the effects of pharmacological agents, such as botulinum toxin. Two independent reviewers assessed the eligibility of each study for inclusion into the review, the study design used and its methodological quality. Where any disagreement occurred, consensus was reached by discussion. Studies were assessed for clinical homogeneity by considering populations, interventions and outcomes. Where heterogeneity was present, synthesis was undertaken in a narrative format. Eight studies were included in the review. Most were ranked low on the Hierarchy of Evidence (no randomised controlled trials were found), and had only fair methodological quality. Conservative management was variable and could consist of active or passive exercise, splints or traction. All studies lacked a clear description of what constituted conservative management, which would not allow the treatment to be replicated in the clinical setting. A variety of outcome instruments were used, none of which had evidence of validity, reliability or sensitivity to detect change. Furthermore, less severely affected infants were selected to receive conservative management. Therefore, it is difficult to draw conclusions regarding the effectiveness of conservative management for infants with obstetric brachial plexus palsy. There is scant, inconclusive evidence regarding the effectiveness of primary conservative intervention for infants with obstetric brachial plexus palsy. Further research should be directed to develop outcome instruments with sound psychometric properties for infants with obstetric brachial plexus palsy and their families. These outcome instruments should then be used in well-designed comparative studies.

Effectiveness of primary conservative management for infants with obstetric brachial plexus palsy.

PubMed

Bialocerkowski, Andrea; Kurlowicz, Kirsty; Vladusic, Sharon; Grimmer, Karen

2005-03-01

Background  Obstetric brachial plexus palsy, a complication of childbirth, occurs in 1-3 per 1000 live births internationally. Traction and/or compression of the brachial plexus is thought to be the primary mechanism of injury and this may occur in utero, during the descent through the birth canal or during delivery. This results in a spectrum of injuries that vary in severity, extent of damage and functional use of the affected upper limb. Most infants receive treatment, such as conservative management (physiotherapy, occupational therapy) or surgery; however, there is controversy regarding the most appropriate form of management. To date, no synthesised evidence is available regarding the effectiveness of primary conservative management for obstetric brachial plexus palsy. Objectives  The objective of this review was to systematically assess the literature and present the best available evidence that investigated the effectiveness of primary conservative management for infants with obstetric brachial plexus palsy. Search strategy  A systematic literature search was performed using 14 databases: TRIP, MEDLINE, CINAHL, AMED, Web of Science, Proquest 5000, Evidence Based Medicine Reviews, Expanded Academic ASAP, Meditext, Science Direct, Physiotherapy Evidence Database, Proquest Digital Dissertations, Open Archives Initiative Search Engine, Australian Digital Thesis Program. Those studies that were reported in English and published over the last decade (July 1992 to June 2003) were included in this review. Selection criteria  Quantitative studies that investigated the effectiveness of primary conservative management for infants with obstetric brachial plexus palsy were eligible for inclusion in this review. This excluded studies that solely investigated the effect of primary surgery for these infants, management of secondary deformities and the investigation of the effects of pharmacological agents, such as botulinum toxin. Data collection and analysis  Two independent reviewers assessed the eligibility of each study for inclusion into the review, the study design used and its methodological quality. Where any disagreement occurred, consensus was reached by discussion. Studies were assessed for clinical homogeneity by considering populations, interventions and outcomes. Where heterogeneity was present, synthesis was undertaken in a narrative format. Results  Eight studies were included in the review. Most were ranked low on the Hierarchy of Evidence (no randomised controlled trials were found), and had only fair methodological quality. Conservative management was variable and could consist of active or passive exercise, splints or traction. All studies lacked a clear description of what constituted conservative management, which would not allow the treatment to be replicated in the clinical setting. A variety of outcome instruments were used, none of which had evidence of validity, reliability or sensitivity to detect change. Furthermore, less severely affected infants were selected to receive conservative management. Therefore, it is difficult to draw conclusions regarding the effectiveness of conservative management for infants with obstetric brachial plexus palsy. Conclusions  There is scant, inconclusive evidence regarding the effectiveness of primary conservative intervention for infants with obstetric brachial plexus palsy. Further research should be directed to develop outcome instruments with sound psychometric properties for infants with obstetric brachial plexus palsy and their families. These outcome instruments should then be used in well-designed comparative studies.

76 FR 59767 - Plexus Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

..., Financings which Constitute Conflicts of Interest of the Small Business Administration (``SBA'') Rules and Regulations (13 CFR 107.730). Plexus II, L.P., proposes to provide debt security financing to Project Empire... the Small Business Investment Act of 1958, as amended (``the Act''), in connection with the financing...

Changes in Spinal Cord Architecture after Brachial Plexus Injury in the Newborn

ERIC Educational Resources Information Center

Korak, Klaus J.; Tam, Siu Lin; Gordon, Tessa; Frey, Manfred; Aszmann, Oskar C.

2004-01-01

Obstetric brachial plexus palsy is a devastating birth injury. While many children recover spontaneously, 20-25% are left with a permanent impairment of the affected limb. So far, concepts of pathology and recovery have focused on the injury of the peripheral nerve. Proximal nerve injury at birth, however, leads to massive injury-induced…

Acute repair of traumatic pan-brachial plexus injury: technical considerations and approaches.

PubMed

Abou-Al-Shaar, Hussam; Karsy, Michael; Ravindra, Vijay; Joyce, Evan; Mahan, Mark A

2018-01-01

Particularly challenging after complete brachial plexus avulsion is reestablishing effective hand function, due to limited neurological donors to reanimate the arm. Acute repair of avulsion injuries may enable reinnervation strategies for achieving hand function. This patient presented with pan-brachial plexus injury. Given its irreparable nature, the authors recommended multistage reconstruction, including contralateral C-7 transfer for hand function, multiple intercostal nerves for shoulder/triceps function, shoulder fusion, and spinal accessory nerve-to-musculocutaneous nerve transfer for elbow flexion. The video demonstrates distal contraction from electrical stimulation of the avulsed roots. Single neurorrhaphy of the contralateral C-7 transfer was performed along with a retrosternocleidomastoid approach. The video can be found here: https://youtu.be/GMPfno8sK0U .

Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.

PubMed

Yang, Mo; Fukui, Hirokazu; Eda, Hirotsugu; Xu, Xin; Kitayama, Yoshitaka; Hara, Ken; Kodani, Mio; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

2017-04-01

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work. Copyright © 2017 the American Physiological Society.

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

Measuring surgeons' treatment preferences and satisfaction with nerve reconstruction techniques for children with unique brachial plexus birth palsies.

PubMed

Shah, Amee K; Zurakowski, David; Jessel, Rebecca H; Kuo, Anne; Waters, Peter M

2006-09-15

This study surveyed microsurgeons on treatments chosen for infants with brachial plexus birth palsies who have had failure of antigravity biceps and/or triceps function due to nerve surgery or natural history. Questionnaires were sent to surgeons participating in a prospective multicenter brachial plexus birth palsy study. With a response rate of 82 percent, the sample comprised 22 surgeons with extensive experience in treating brachial plexus birth palsy. The survey gathered collective information on two unique clinical groups: (1) infants with no antigravity biceps function but intact antigravity deltoid and radial nerve function and (2) infants with no antigravity radial nerve function (wrist and digital extension, triceps) but intact antigravity biceps and deltoid function. Analysis of data and age-based trends was performed using the Fisher's exact test. With failure of biceps recovery, surgeons preferred microsurgery for children 6 to 18 months old and tendon transfers for children older than 18 months. Both procedures were preferred over observation alone (p < 0.001). With regard to microsurgery techniques, with increasing age, surgeons used nerve transfers more than resected neuroma and grafting. With tendon transfers, regional transfers were performed more than 90 percent of the time at all ages. For patients with no antigravity radial nerve function, most cases at all ages were managed by observation rather than microsurgery or tendon transfers (p < 0.001). The authors' data indicate a general consensus in treatment choices for the two cases of microsurgical failure in infants with brachial plexus birth palsies as well as in satisfaction among experienced surgeons in using these treatments.

[Prophylactic plexus catheter treatment in operations following complex regional pain syndrome (CRPS)].

PubMed

Neubrech, Florian; Pronk, Roderick Franciscus; Bigdeli, Amir Khosrow; Tapking, Christian; Kneser, Ulrich; Harhaus, Leila

2017-08-01

Background  This paper investigates and discusses the effect of perioperative plexus catheter treatment in former CRPS patients. Patients and Methods A retrospective matched-pair analysis was conducted on 10 CRPS patients with comparable injuries, who underwent surgery in the disease-free interval. In 10 cases, the procedure was performed with perioperative plexus catheter treatment (intervention group), whereas 10 patients did not receive perioperative plexus catheter treatment (control group). Results  In the intervention group, after a follow-up time of 105 (20-184) days after the last surgical procedure, pain intensity on the visual analogue scale (VAS; 0 to 10) was 6.4 (4-8), fingertip-to-palm distance averaged 3.2 (0-7.6) cm, active range of wrist motion was 47.5 (0-95), and grip strength was 9.2 (2.1-16.6) kg. In the control group, after a follow-up time of 129 (19-410) days since the last surgical procedure, pain intensity on the visual analogue scale was 6 (3-10), fingertip-to-palm distance averaged 2.7 (0-4.5) cm, active range of wrist-motion was 64 (0-125), and grip strength was 12.4 (0.8-23.8) kg. There was no significant difference between the groups. There was no recurrence of CRPS disease in either group after surgery. Conclusion  There is no evidence so far for perioperative plexus catheter treatment to prevent recurrence in former CRPS patients. Georg Thieme Verlag KG Stuttgart · New York.

Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary symptoms.

PubMed

Lemos, Nucelio; Marques, Renato Moretti; Kamergorodsky, Gil; Ploger, Christine; Schor, Eduardo; Girão, Manoel J B C

2016-02-01

Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves. Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots. After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms. The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.

A novel combination of peripheral nerve blocks for arthroscopic shoulder surgery.

PubMed

Musso, D; Flohr-Madsen, S; Meknas, K; Wilsgaard, T; Ytrebø, L M; Klaastad, Ø

2017-10-01

Interscalene brachial plexus block is currently the gold standard for intra- and post-operative pain management for patients undergoing arthroscopic shoulder surgery. However, it is associated with block related complications, of which effect on the phrenic nerve have been of most interest. Side effects caused by general anesthesia, when this is required, are also a concern. We hypothesized that the combination of superficial cervical plexus block, suprascapular nerve block, and infraclavicular brachial plexus block would provide a good alternative to interscalene block and general anesthesia. Twenty adult patients scheduled for arthroscopic shoulder surgery received a combination of superficial cervical plexus block (5 ml ropivacaine 0.5%), suprascapular nerve block (4 ml ropivacaine 0.5%), and lateral sagittal infraclavicular block (31 ml ropivacaine 0.75%). The primary aim was to find the proportion of patients who could be operated under light propofol sedation, without the need for opioids or artificial airway. Secondary aims were patients' satisfaction and surgeons' judgment of the operating conditions. Nineteen of twenty patients (95% CI: 85-100) underwent arthroscopic shoulder surgery with light propofol sedation, but without opioids or artificial airway. The excluded patient was not comfortable in the beach chair position and therefore received general anesthesia. All patients were satisfied with the treatment on follow-up interviews. The surgeons rated the operating conditions as good for all patients. The novel combination of a superficial cervical plexus block, a suprascapular nerve block, and an infraclavicular nerve block provides an alternative anesthetic modality for arthroscopic shoulder surgery. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Clinical and neuropathological study about the neurotization of the suprascapular nerve in obstetric brachial plexus lesions

PubMed Central

2009-01-01

Background The lack of recovery of active external rotation of the shoulder is an important problem in children suffering from brachial plexus lesions involving the suprascapular nerve. The accessory nerve neurotization to the suprascapular nerve is a standard procedure, performed to improve shoulder motion in patients with brachial plexus palsy. Methods We operated on 65 patients with obstetric brachial plexus palsy (OBPP), aged 5-35 months (average: 19 months). We assessed the recovery of passive and active external rotation with the arm in abduction and in adduction. We also looked at the influence of the restoration of the muscular balance between the internal and the external rotators on the development of a gleno-humeral joint dysplasia. Intraoperatively, suprascapular nerve samples were taken from 13 patients and were analyzed histologically. Results Most patients (71.5%) showed good recovery of the active external rotation in abduction (60°-90°). Better results were obtained for the external rotation with the arm in abduction compared to adduction, and for patients having only undergone the neurotization procedure compared to patients having had complete plexus reconstruction. The neurotization operation has a positive influence on the glenohumeral joint: 7 patients with clinical signs of dysplasia before the reconstructive operation did not show any sign of dysplasia in the postoperative follow-up. Conclusion The neurotization procedure helps to recover the active external rotation in the shoulder joint and has a good prevention influence on the dysplasia in our sample. The nerve quality measured using histopathology also seems to have a positive impact on the clinical results. PMID:19744351

Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rates of replenishment in bone marrow chimeric mice.

PubMed

Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

2010-09-01

The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx3cr1 knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX3CR1 on their number and tissue distribution. Iba-1 major histocompatibility complex (MHC) Class II CD169 CD68 macrophages and CD11c putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx3cr1 mice did not reveal CX3CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx3cr1/-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX3CR1-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.

Lumbar plexus block using high-pressure injection leads to contralateral and epidural spread.

PubMed

Gadsden, Jeff C; Lindenmuth, Danielle M; Hadzic, Admir; Xu, Daquan; Somasundarum, Lakshmanasamy; Flisinski, Kamil A

2008-10-01

The main advantage of lumbar plexus block over neuraxial anesthesia is unilateral blockade; however, the relatively common occurrence of bilateral spread (up to 27%) makes this advantage unpredictable. The authors hypothesized that high injection pressures during lumbar plexus block carry a higher risk of bilateral or neuraxial anesthesia. Eighty patients undergoing knee arthroscopy (age 18-65 yr; American Society of Anesthesiologists physical status I or II) during a standard, nerve stimulator-guided lumbar plexus block using 35 ml mepivacaine, 1.5%, were scheduled to be studied. Patients were randomly assigned to receive either a low-pressure (< 15 psi) or a high-pressure (> 20 psi) injection, as assessed by an inline injection pressure monitor (BSmart; Concert Medical LLC, Norwell, MA). The block success rate and the presence of bilateral sensory and/or motor blockade were assessed. An interim analysis was performed at n = 20 after an unexpectedly high number of patients had neuraxial spread, necessitating early termination of the study. Five of 10 patients (50%) in the high-pressure group had a neuraxial block with a dermatomal sensory level T10 or higher. In contrast, no patient in the low-pressure group (n = 10) had evidence of neuraxial spread. Moreover, 6 patients (60%) in the high-pressure group demonstrated bilateral sensory blockade in the femoral distribution, whereas no patient in the low-pressure group had evidence of a bilateral femoral block. Injection of local anesthetic with high injection pressure (> 20 psi) during lumbar plexus block commonly results in unwanted bilateral blockade and is associated with high risk of neuraxial blockade.

Three-dimensional venous anatomy of the dermis observed using stereography

PubMed Central

Imanishi, Nobuaki; Kishi, Kazuo; Chang, Hak; Nakajima, Hideo; Aiso, Sadakazu

2008-01-01

Veins of the dermis have been investigated mainly by histological methods in the fields of anatomy and histology, and a large number of schemata of the veins have been depicted in a variety of textbooks. However, the schemata are usually two-dimensional and it is therefore difficult to envisage the actual vasculature of the dermal veins. In this study, we performed a stereographic study of the skin of three fresh cadavers that had been injected with radio-opaque dye, which was dispersed throughout the entire body. A venous network consisting of venous polygons of various sizes existed just under the dermis or in the deep zone of the dermis, which is generally called the subdermal venous plexus. There were many small vessels towards the inside of each venous polygon, and most of them ascended, branching off stereoscopically. Those branches anastomosed with each other, and they formed the dermal and subpapillary venous plexuses. However, there was little vascular connection between dermal venous plexuses of different venous polygons. The characteristic structure of the dermal venous plexus has been considered to bring about venous congestion of the skin in various clinical situations. PMID:18422525

Intracranial distribution of the sympathetic system in mice: DiI tracing and immunocytochemical labeling

NASA Technical Reports Server (NTRS)

Maklad, A.; Quinn, T.; Fritzsch, B.

2001-01-01

The intracranial distribution of the cephalic branches of the superior cervical ganglion (scg) was studied in mice using indocarbocyanine dye (DiI) anterograde tracing. Two main branches were traced from the scg. The first branch joined the nerve of the pterygoid canal (the vidian nerve), npc, from which several intracranial sympathetic branches passed to the branches of the trigeminal nerve (tgn), abducent nerve (abn), trochlear nerve (trn), and oculomotor nerve (ocn). Most of the second branch joined the abn, from which sympathetic fibers dispersed in the distal region of the trigeminal ganglion (tgg) to form a plexus close to the ganglion's branches. Branches from this plexus joined the branches of the tgn, trn, and ocn. Several minor branches arising from the second branch of the scg were also observed. One formed a sympathetic plexus around the internal carotid artery (ica); a second formed a sympathetic plexus in the proximal region of tgg, close to its root; and a third branch coursed laterally to reach the ear by passing along the greater petrosal nerve (gpn). All of the intracranial trajectories traced from scg were found to be catecholaminergic, and likely sympathetic, using tyrosine hydroxylase (TH) immunocytochemistry.

Obstetric brachial plexus injury

PubMed Central

Thatte, Mukund R.; Mehta, Rujuta

2011-01-01

Obstetric brachial plexus injury (OBPI), also known as birth brachial plexus injury (BBPI), is unfortunately a rather common injury in newborn children. Incidence varies between 0.15 and 3 per 1000 live births in various series and countries. Although spontaneous recovery is known, there is a large subset which does not recover and needs primary or secondary surgical intervention. An extensive review of peer-reviewed publications has been done in this study, including clinical papers, review articles and systematic review of the subject. In addition, the authors’ experience of several hundred cases over the last 15 years has been added and has influenced the ultimate text. Causes of OBPI, indications of primary nerve surgery and secondary reconstruction of shoulder, etc. are discussed in detail. Although all affected children do not require surgery in infancy, a substantial proportion of them, however, require it and are better off for it. Secondary surgery is needed for shoulder elbow and hand problems. Results of nerve surgery are very encouraging. Children with OBPI should be seen early by a hand surgeon dealing with brachial plexus injuries. Good results are possible with early and appropriate intervention even in severe cases. PMID:22279269

[Complications in brachial plexus surgery].

PubMed

Martínez, Fernando; Pinazzo, Samantha; Moragues, Rodrigo; Suarez, Elizabeth

2015-01-01

Although traumatic brachial plexus injuries are relatively rare in trauma patients, their effects on the functionality of the upper limb can be very disabling. The authors' objective was to assess the complications in a series of patients operated for brachial plexus injuries. This was a retrospective evaluation of patients operated on by the authors between August 2009 and March 2013. We performed 36 surgeries on 33 patients. The incidence of complications was 27.7%. Of these, only 1 (2.7%) was considered serious and associated with the procedure (iatrogenic injury of brachial artery). There was another serious complication (hypoxia in patients with airway injury) but it was not directly related to the surgical procedure. All other complications were considered minor (wound dehiscence, hematoma, infection). There was no mortality in our series. The complications in our series are similar to those reported in the literature. Serious complications (vascular, neural) are rare and represent less than 5% in all the different series. Given the rate of surgical complications and the poor functional perspective for a brachial plexus injury without surgery, we believe that surgery should be the treatment of choice. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Retrieval of optical properties of skin from measurement and modeling the diffuse reflectance

NASA Astrophysics Data System (ADS)

Douven, Lucien F. A.; Lucassen, Gerald W.

2000-06-01

We present results on the retrieval of skin optical properties obtained by fitting of measurements of the diffuse reflectance of human skin. Reflectance spectra are simulated using an analytical model based on the diffusion approximation. This model is implemented in a simplex fit routine. The skin optical model used consists of five layers representing epidermis, capillary blood plexus, dermis, deep blood plexus and hypodermis. The optical properties of each layer are assumed homogeneously distributed. The main optical absorbers included are melanin in epidermis and blood. The experimental setup consists of a HP photospectrometer equipped with a remote fiber head. Total reflectance spectra were measured in the 400 - 820 nm wavelength range on the volar underarm of 19 volunteers under various conditions influencing the blood content and oxygenation degree. Changes in the reflectance spectra were observed. Using the fit routine changes in blood content in the capillary blood plexus and in the deep blood plexus could be quantified. These showed different influences on the total reflectance. The method can be helpful to quantitatively assess changes in skin color appearance such as occurs in the treatment of port wine stains, blanching, skin irritation and tanning.

Variations of the origin of collateral branches emerging from the posterior aspect of the brachial plexus

PubMed Central

2007-01-01

Background The frequency of variation found in the arrangement and distribution of the branches in the brachial plexus, make this anatomical region extremely complicated. The medical concerns involved with these variations include anesthetic blocks, surgical approaches, interpreting tumor or traumatic nervous compressions having unexplained clinical symptoms (sensory loss, pain, wakefulness and paresis), and the possibility of these structures becoming compromised. The clinical importance of these variations is discussed in the light of their differential origins. Methods The anatomy of brachial plexus structures from 46 male and 11 female cadaverous specimens were studied. The 40–80 year-old specimens were obtained from the Universidad Industrial de Santander's Medical Faculty's Anatomy Department (dissection laboratory). Parametric measures were used for calculating results. Results Almost half (47.1%) of the evaluated plexuses had collateral variations. Subscapular nerves were the most varied structure, including the presence of a novel accessory nerve. Long thoracic nerve variations were present, as were the absence of C5 or C7 involvement, and late C7 union with C5–C6. Conclusion Further studies are needed to confirm the existence of these variations in a larger sample of cadaver specimens. PMID:17587464

Neurotization of elements of the brachial plexus.

PubMed

Friedman, A H

1991-01-01

Satisfactory therapy for an avulsion injury of the brachial plexus has yet to be described. Dorsal root entry zone lesions will usually mitigate the searing pain which is so disabling in some of these patients. Neurotization procedures are effective in restoring limited function to these patients. The most useful isolated movement of the upper extremity is elbow flexion, which is thus the primary target of neurotization procedures. Intercostal nerves and elements of the cervical plexus are the most commonly used donor nerves for neurotization procedures. From our experience and from a review of the literature, it appears that these procedures will be successful in approximately 50% of cases. It must be stressed that before performing a nerve transfer, the surgeon must be certain that the patient is not a candidate for a simple nerve graft.

Association Between Vessel Density and Visual Acuity in Patients With Diabetic Retinopathy and Poorly Controlled Type 1 Diabetes.

PubMed

Dupas, Bénédicte; Minvielle, Wilfried; Bonnin, Sophie; Couturier, Aude; Erginay, Ali; Massin, Pascale; Gaudric, Alain; Tadayoni, Ramin

2018-05-10

Capillary dropout is a hallmark of diabetic retinopathy, but its role in visual loss remains unclear. To examine how macular vessel density is correlated with visual acuity (VA) in patients younger than 40 years who have type 1 diabetes without macular edema but who have diabetic retinopathy requiring panretinal photocoagulation. Retrospective cohort study of VA and optical coherence tomography angiography data collected from consecutive patients during a single visit to Lariboisière Hospital, a tertiary referral center in Paris, France. The cohort included 22 eyes of 22 patients with type 1 diabetes without macular edema but with bilateral rapidly progressive diabetic retinopathy that was treated with panretinal photocoagulation between August 15, 2015, and December 30, 2016. Eyes were classified into 2 groups by VA: normal (logMAR, 0; Snellen equivalent, 20/20) and decreased (logMAR, >0; Snellen equivalent, <20/20). The control group included 12 eyes from age-matched healthy participants with normal vision. Visual acuity and mean vessel density in 4 retinal vascular plexuses: the superficial vascular plexus and the deep capillary complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Of the 22 participants, 11 (50%) were men, mean (SD) age was 30 (6) years, and mean (SD) hemoglobin A1c level was 8.9% (1.6%). Of the 22 eyes with diabetic retinopathy, 13 (59%) had normal VA and 9 (41%) had decreased VA (mean [SD]: logMAR, 0.12 [0.04]; Snellen equivalent, 20/25). Mean [SE] vessel density was lower for eyes with diabetic retinopathy and normal VA compared with the control group in the superficial vascular plexus (44.1% [0.9%] vs 49.1% [0.9%]; difference, -5.0% [1.3%]; 95% CI, -7.5% to -2.4%; P < .001), in the deep capillary complex (44.3% [1.2%] vs 50.6% [1.3%]; difference, -6.3% [1.8%]; 95% CI, -9.9% to -2.7%; P = .001), in the intermediate capillary plexus (43.8% [1.2%] vs 49.3% [1.2%]; difference, -5.5% [1.7%]; 95% CI, -9.0% to -2.0%; P = .003), and in the deep capillary plexus (24.5% [1.0%] vs 30.5% [1.0%]; difference, -6.1% [1.4%]; 95% CI, -8.9% to -3.2%; P < .001). Mean vessel density was lower in eyes with diabetic retinopathy and decreased VA compared with eyes with diabetic retinopathy and normal VA; the mean (SE) loss was more pronounced in the deep capillary complex (34.6% [1.5%] vs 44.3% [1.2%]; difference, -9.6% [1.9%]; 95% CI, -13.6% to -5.7%; P < .001), especially in the deep capillary plexus (15.2% [1.2%] vs 24.5% [1.0%]; difference, -9.3% [1.5%]; 95% CI, -12.4% to -6.1%; P < .001), than in the superficial vascular plexus (39.6% [1.1%] vs 44.1% [0.9%]; difference, -4.5% [1.4%]; 95% CI, -7.3% to -1.7%; P = .002). These data suggest that in patients with type 1 diabetes without macular edema but with severe nonproliferative or proliferative diabetic retinopathy, decreased VA may be associated with the degree of capillary loss in the deep capillary complex.

Defining the safe working zones using the minimally invasive lateral retroperitoneal transpsoas approach: an anatomical study.

PubMed

Uribe, Juan S; Arredondo, Nicolas; Dakwar, Elias; Vale, Fernando L

2010-08-01

The lateral retroperitoneal transpsoas approach is being increasingly employed to treat various spinal disorders. The minimally invasive blunt retroperitoneal and transpsoas dissection poses a risk of injury to major nervous structures. The addition of electrophysiological monitoring potentially decreases the risk of injury to the lumbar plexus. With respect to the use of the direct transpsoas approach, however, there is sparse knowledge regarding the relationship between the retroperitoneum/psoas muscle and the lumbar plexus at each lumbar segment. The authors undertook this anatomical cadaveric dissection study to define the anatomical safe zones relative to the disc spaces for prevention of nerve injuries during the lateral retroperitoneal transpsoas approach. Twenty lumbar segments were dissected and studied. The relationship between the retroperitoneum, psoas muscle, and the lumbar plexus was analyzed. The area between the anterior and posterior edges of the vertebral body (VB) was divided into 4 equal zones. Radiopaque markers were placed in each disc space at the midpoint of Zone III (middle posterior quarter). At each segment, the psoas muscle, lumbar plexus, and nerve roots were dissected. The distribution of the lumbar plexus with reference to the markers at each lumbar segment was analyzed. All parts of the lumbar plexus, including nerve roots, were found within the substance of the psoas muscle dorsal to the posterior fourth of the VB (Zone IV). No Zone III marker was posterior to any part of the lumbar plexus with the exception of the genitofemoral nerve. The genitofemoral nerve travels obliquely in the substance of the psoas muscle from its origin to its innervations. It emerges superficially and anterior from the medial border of the psoas at the L3-4 level and courses along the anterior medial fourth of the L-4 and L-5 VBs (Zone I). The nerves of the plexus that originate at the upper lumbar segments emerge from the lateral border of the psoas major and cross obliquely into the retroperitoneum in front of the quadratus lumborum and the iliacus muscles to the iliac crest. With respect to prevention of direct nerve injury, the safe anatomical zones at the disc spaces from L1-2 to L3-4 are at the middle posterior quarter of the VB (midpoint of Zone III) and the safe anatomical zone at the L4-5 disc space is at the midpoint of the VB (Zone II-Zone III demarcation). There is risk of direct injury to the genitofemoral nerve in Zone II at the L2-3 space and in Zone I at the lower lumbar levels L3-4 and L4-5. There is also a potential risk of injury to the ilioinguinal, iliohypogastric, and lateral femoral cutaneous nerves in the retroperitoneal space where they travel obliquely, inferiorly, and anteriorly to the reach the iliac crest and the abdominal wall.

Vascular endothelial growth factor gene therapy improves nerve regeneration in a model of obstetric brachial plexus palsy.

PubMed

Hillenbrand, Matthias; Holzbach, Thomas; Matiasek, Kaspar; Schlegel, Jürgen; Giunta, Riccardo E

2015-03-01

The treatment of obstetric brachial plexus palsy has been limited to conservative therapies and surgical reconstruction of peripheral nerves. In addition to the damage of the brachial plexus itself, it also leads to a loss of the corresponding motoneurons in the spinal cord, which raises the need for supportive strategies that take the participation of the central nervous system into account. Based on the protective and regenerative effects of VEGF on neural tissue, our aim was to analyse the effect on nerve regeneration by adenoviral gene transfer of vascular endothelial growth factor (VEGF) in postpartum nerve injury of the brachial plexus in rats. In the present study, we induced a selective crush injury to the left spinal roots C5 and C6 in 18 rats within 24 hours after birth and examined the effect of VEGF-gene therapy on nerve regeneration. For gene transduction an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) was used. In a period of 11 weeks, starting 3 weeks post-operatively, functional regeneration was assessed weekly by behavioural analysis and force measurement of the upper limb. Morphometric evaluation was carried out 8 months post-operatively and consisted of a histological examination of the deltoid muscle and the brachial plexus according to defined criteria of degeneration. In addition, atrophy of the deltoid muscle was evaluated by weight determination comparing the left with the right side. VEGF expression in the brachial plexus was quantified by an enzyme-linked immunosorbent assay (ELISA). Furthermore the motoneurons of the spinal cord segment C5 were counted comparing the left with the right side. On the functional level, VEGF-treated animals showed faster nerve regeneration. It was found less degeneration and smaller mass reduction of the deltoid muscle in VEGF-treated animals. We observed significantly less degeneration of the brachial plexus and a greater number of surviving motoneurons (P < 0·05) in the VEGF group. The results of this study confirmed the positive effect of VEGF-gene therapy on regeneration and survival of nerve cells. We could demonstrate a significant improvement on the motor-functional as well as on the histomorphological level. However, increased vascularization of the nerve tissue caused by VEGF does not seem to be the major reason for these effects. The clinical use of adenoviral VEGF-gene therapy in the newborn cannot be justified so far.

The heritability of vessel size of the pampiniform plexus as a means to assess the genetic component of varicocele

USDA-ARS?s Scientific Manuscript database

Ultrasonography of each testicle was used to capture a coronal-saggital image of the veins of the pampiniform plexus (PP) and the testicular artery of 239 boars at approximately 6 months of age. Three to 10 vessels of the PP were used to derive the average area of right PP vessels (AAR) and the aver...

Psoas compartment and sacral plexus block via electrostimulation for pelvic limb amputation in dogs.

PubMed

Congdon, Jonathon M; Boscan, Pedro; Goh, Clara S S; Rezende, Marlis

2017-07-01

To assess the efficacy of psoas compartment and sacral plexus block for pelvic limb amputation in dogs. Prospective clinical study. A total of 16 dogs aged 8±3 years and weighing 35±14 kg (mean±standard deviation). Dogs were administered morphine (0.5 mg kg -1 ) and atropine (0.02 mg kg -1 ); anesthesia was induced with propofol and maintained with isoflurane. Regional blocks were performed before surgery in eight dogs with bupivacaine (2.2 mg kg -1 ) and eight dogs were administered an equivalent volume of saline. The lumbar plexus within the psoas compartment was identified using electrolocation lateral to the lumbar vertebrae at the fourth-fifth, fifth-sixth and sixth-seventh vertebral interspaces. The sacral plexus, ventrolateral to the sacrum, was identified using electrolocation. Anesthesia was monitored using heart rate (HR), invasive blood pressure, electrocardiography, expired gases, respiratory frequency and esophageal temperature by an investigator unaware of the group allocation. Pelvic limb amputation by coxofemoral disarticulation was performed. Dogs that responded to surgical stimulation (>10% increase in HR or arterial pressure) were administered fentanyl (2 μg kg -1 ) intravenously for rescue analgesia. Postoperative pain was assessed at extubation; 30, 60 and 120 minutes; and the morning after surgery using a visual analog scale (VAS). The number of intraoperative fentanyl doses was fewer in the bupivacaine group (2.7±1.1 versus 6.0±2.2; p<0.01). Differences in physiologic variables were not clinically significant. VAS scores were lower in bupivacaine dogs at extubation (0.8±1.9 versus 3.8±2.5) and at 30 minutes (1.0±1.4 versus 4.3±2.1; p<0.05). Psoas compartment (lumbar plexus) and sacral plexus block provided analgesia during pelvic limb amputation in dogs. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Perinatal brachial plexus palsy

PubMed Central

Andersen, John; Watt, Joe; Olson, Jaret; Van Aerde, John

2006-01-01

BACKGROUND Perinatal brachial plexus palsy (PBPP) is a flaccid paralysis of the arm at birth that affects different nerves of the brachial plexus supplied by C5 to T1 in 0.42 to 5.1 infants per 1000 live births. OBJECTIVES To identify antenatal factors associated with PBPP and possible preventive measures, and to review the natural history as compared with the outcome after primary or secondary surgical interventions. METHODS A literature search on randomized controlled trials, systematic reviews and meta-analyses on the prevention and treatment of PBPP was performed. EMBASE, Medline, CINAHL and the Cochrane Library were searched until June 2005. Key words for searches included ‘brachial plexus’, ‘brachial plexus neuropathy’, ‘brachial plexus injury’, ‘birth injury’ and ‘paralysis, obstetric’. RESULTS There were no prospective studies on the cause or prevention of PBPP. Whereas birth trauma is said to be the most common cause, there is some evidence that PBPP may occur before delivery. Shoulder dystocia and PBPP are largely unpredictable, although associations of PBPP with shoulder dystocia, infants who are large for gestational age, maternal diabetes and instrumental delivery have been reported. The various forms of PBPP, clinical findings and diagnostic measures are described. Recent evidence suggests that the natural history of PBPP is not all favourable, and residual deficits are estimated at 20% to 30%, in contrast with the previous optimistic view of full recovery in greater than 90% of affected children. There were no randomized controlled trials on nonoperative management. There was no conclusive evidence that primary surgical exploration of the brachial plexus supercedes conservative management for improved outcome. However, results from nonrandomized studies indicated that children with severe injuries do better with surgical repair. Secondary surgical reconstructions were inferior to primary intervention, but could still improve arm function in children with serious impairments. CONCLUSIONS It is not possible to predict which infants are at risk for PBPP, and therefore amenable to preventive measures. Twenty-five per cent of affected infants will experience permanent impairment and injury. If recovery is incomplete by the end of the first month, referral to a multidisciplinary team is necessary. Further research into prediction, prevention and best mode of treatment needs to be done. PMID:19030261

Systemic Gene Delivery Transduces the Enteric Nervous System of Guinea Pigs and Cynomolgus Macaques

PubMed Central

Gombash, Sara E; Cowley, Christopher J; Fitzgerald, Julie A; Lepak, Christina A; Neides, Mitchell G; Hook, Kathryn; Todd, Levi J; Wang, Guo-Du; Mueller, Christian; Kaspar, Brian K; Bielefeld, Eric C; Fischer, Andrew J; Wood, Jackie D; Foust, Kevin D

2017-01-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9 treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders. PMID:28771235

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

PubMed

Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

2017-10-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

Depression and Anxiety in Traumatic Brachial Plexus Injury Patients Are Associated With Reduced Motor Outcome After Surgical Intervention for Restoration of Elbow Flexion.

PubMed

Wilson, Thomas J; Chang, Kate W C; Yang, Lynda J-S

2016-06-01

Depression has been associated with poor outcomes in neurosurgical patients, including increased pain, poorer functional recovery, delayed return to work, and decreased patient satisfaction. No reports exist regarding an association of psychiatric diagnoses with outcomes after brachial plexus reconstruction. As outcomes and patient satisfaction become increasingly important to payers and physician reimbursement, assessing modifiable preoperative risk factors for their association with poor outcome and patient satisfaction is imperative. To analyze patients undergoing brachial plexus reconstruction to assess the relationship of depression/anxiety with functional outcome. Data were collected retrospectively on all patients who underwent brachial plexus reconstruction to restore elbow flexion between 2005 and 2013. Elbow flexion, graded via the Medical Research Council scale, was assessed at latest follow-up. Multiple variables, including the presence of Axis I psychiatric diagnoses, were assessed for their association with the dichotomous outcome of Medical Research Council scale score ≥3 (antigravity) vs <3 elbow flexion. Standard statistical methods were used. Thirty-seven patients met inclusion criteria. The median postsurgical follow-up time was 21 months. Operations included neurolysis (n = 3), nerve graft repair (n = 6), and nerve transfer (n = 28). Depression was present in 10 of 37 patients (27%). Of variables tested, only depression was associated with poor elbow flexion outcome (odds ratio: 6.038; P = .04). Preoperative depression is common after brachial plexus injury. The presence of depression is associated with reduced elbow flexion recovery after reconstruction. Our data suggest assessment and treatment of preoperative mental health is important in designing a comprehensive postoperative management plan to optimize outcomes and patient satisfaction. MRC, Medical Research CouncilTBI, traumatic brain injury.

Ultrasound-guided approach for axillary brachial plexus, femoral nerve, and sciatic nerve blocks in dogs.

PubMed

Campoy, Luis; Bezuidenhout, Abraham J; Gleed, Robin D; Martin-Flores, Manuel; Raw, Robert M; Santare, Carrie L; Jay, Ariane R; Wang, Annie L

2010-03-01

To describe an ultrasound-guided technique and the anatomical basis for three clinically useful nerve blocks in dogs. Prospective experimental trial. Four hound-cross dogs aged 2 +/- 0 years (mean +/- SD) weighing 30 +/- 5 kg and four Beagles aged 2 +/- 0 years and weighing 8.5 +/- 0.5 kg. Axillary brachial plexus, femoral, and sciatic combined ultrasound/electrolocation-guided nerve blocks were performed sequentially and bilaterally using a lidocaine solution mixed with methylene blue. Sciatic nerve blocks were not performed in the hounds. After the blocks, the dogs were euthanatized and each relevant site dissected. Axillary brachial plexus block Landmark blood vessels and the roots of the brachial plexus were identified by ultrasound in all eight dogs. Anatomical examination confirmed the relationship between the four ventral nerve roots (C6, C7, C8, and T1) and the axillary vessels. Three roots (C7, C8, and T1) were adequately stained bilaterally in all dogs. Femoral nerve block Landmark blood vessels (femoral artery and femoral vein), the femoral and saphenous nerves and the medial portion of the rectus femoris muscle were identified by ultrasound in all dogs. Anatomical examination confirmed the relationship between the femoral vessels, femoral nerve, and the rectus femoris muscle. The femoral nerves were adequately stained bilaterally in all dogs. Sciatic nerve block. Ultrasound landmarks (semimembranosus muscle, the fascia of the biceps femoris muscle and the sciatic nerve) could be identified in all of the dogs. In the four Beagles, anatomical examination confirmed the relationship between the biceps femoris muscle, the semimembranosus muscle, and the sciatic nerve. In the Beagles, all but one of the sciatic nerves were stained adequately. Ultrasound-guided needle insertion is an accurate method for depositing local anesthetic for axillary brachial plexus, femoral, and sciatic nerve blocks.

Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

PubMed

Novotny, A; Xiang, J; Stummer, W; Teuscher, N S; Smith, D E; Keep, R F

2000-07-01

5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[(3)H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na(+)-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an alpha-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na(+) and HCO(3)(-) dependent and appears to be an organic anion transporter, although it is possible that removal of Na(+) and HCO(3)(-) may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na(+)/HCO(3)(-)-dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Retropharyngeal Contralateral C7 Nerve Transfer to the Lower Trunk for Brachial Plexus Birth Injury: Technique and Results.

PubMed

Vu, Anthony T; Sparkman, Darlene M; van Belle, Christopher J; Yakuboff, Kevin P; Schwentker, Ann R

2018-05-01

Brachial plexus birth injuries with multiple nerve root avulsions present a particularly difficult reconstructive challenge because of the limited availability of donor nerves. The contralateral C7 has been described for brachial plexus reconstruction in adults but has not been well-studied in the pediatric population. We present our technique and results for retropharyngeal contralateral C7 nerve transfer to the lower trunk for brachial plexus birth injury. We performed a retrospective review. Any child aged less than 2 years was included. Charts were analyzed for patient demographic data, operative variables, functional outcomes, complications, and length of follow-up. We had a total of 5 patients. Average nerve graft length was 3 cm. All patients had return of hand sensation to the ulnar nerve distribution as evidenced by a pinch test, unprompted use of the recipient limb without mirror movement, and an Active Movement Scale (AMS) of at least 2/7 for finger and thumb flexion; one patient had an AMS of 7/7 for finger and thumb flexion. Only one patient had return of ulnar intrinsic hand function with an AMS of 3/7. Two patients had temporary triceps weakness in the donor limb and one had clinically insignificant temporary phrenic nerve paresis. No complications were related to the retropharyngeal nerve dissection in any patient. Average follow-up was 3.3 years. The retropharyngeal contralateral C7 nerve transfer is a safe way to supply extra axons to the severely injured arm in brachial plexus birth injuries with no permanent donor limb deficits. Early functional recovery in these patients, with regard to hand function and sensation, is promising. Therapeutic V. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Radiation Therapy to the Plexus Brachialis in Breast Cancer Patients: Analysis of Paresthesia in Relation to Dose and Volume.

PubMed

Lundstedt, Dan; Gustafsson, Magnus; Steineck, Gunnar; Sundberg, Agnetha; Wilderäng, Ulrica; Holmberg, Erik; Johansson, Karl-Axel; Karlsson, Per

2015-06-01

To identify volume and dose predictors of paresthesia after irradiation of the brachial plexus among women treated for breast cancer. The women had breast surgery with axillary dissection, followed by radiation therapy with (n=192) or without irradiation (n=509) of the supraclavicular lymph nodes (SCLNs). The breast area was treated to 50 Gy in 2.0-Gy fractions, and 192 of the women also had 46 to 50 Gy to the SCLNs. We delineated the brachial plexus on 3-dimensional dose-planning computerized tomography. Three to eight years after radiation therapy the women answered a questionnaire. Irradiated volumes and doses were calculated and related to the occurrence of paresthesia in the hand. After treatment with axillary dissection with radiation therapy to the SCLNs 20% of the women reported paresthesia, compared with 13% after axillary dissection without radiation therapy, resulting in a relative risk (RR) of 1.47 (95% confidence interval [CI] 1.02-2.11). Paresthesia was reported by 25% after radiation therapy to the SCLNs with a V40 Gy ≥ 13.5 cm(3), compared with 13% without radiation therapy, RR 1.83 (95% CI 1.13-2.95). Women having a maximum dose to the brachial plexus of ≥55.0 Gy had a 25% occurrence of paresthesia, with RR 1.86 (95% CI 0.68-5.07, not significant). Our results indicate that there is a correlation between larger irradiated volumes of the brachial plexus and an increased risk of reported paresthesia among women treated for breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the Lumbosacral Plexus Nerves Formation in Pampas Fox (Pseudalopex gymnocercus) and Crab-Eating Fox (Cerdocyon thous) in Relationship to Plexus Model in Dogs.

PubMed

Lorenzão, Caio José; Zimpel, Aline Veiga; Novakoski, Eduardo; da Silva, Aline Alves; Martinez-Pereira, Malcon Andrei

2016-03-01

In this study, the spinal nerves that constitute the lumbosacral plexus (LSP) were dissected in two species of South American wild canids (pampas fox-Pseudalopex gymnocercus, and crab-eating fox-Cerdocyon thous). The nerves origin and distribution in the pelvic limb were examined and compared with the LSP model of the dog described in the literature. The LSP was formed by whole ventral branches of L5 at L7 and S1, and a contribution of a one branch from S2, divided in three trunks. The trunk formed by union from L5-6 and S1 was divided into the cranial (cutaneus femoris lateralis nerve) medial (femoralis nerve) and lateral branches (obturatorius nerve). At the caudal part of the plexus, a thick branch, the ischiadicus plexus, was formed by contributions from L6-7 and S1-2. This root gives rise to the nerve branches which was disseminated to the pelvic limb (nerves gluteus cranial and gluteus caudal, cutaneus femoris caudalis and ischiadicus). The ischiadicus nerve was divided into fibularis communis and tibialis nerves. The tibialis nerve emits the cutaneus surae caudalis. The fibularis communis emits the cutaneus surae lateralis, fibularis superficialis and fibularis profundus. The pudendus nerve arises from S2 with contributions of one branch L7-S1 and one ramus of the cutaneus femoris lateralis. Still, one branch of S2 joins with S3 to form the rectales caudales nerve. These data provides an important anatomical knowledge of a two canid species of South American fauna, besides providing the effective surgical and clinical care of these animals. © 2016 Wiley Periodicals, Inc.

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum

PubMed Central

Saburkina, Inga; Gukauskiene, Ligita; Rysevaite, Kristina; Brack, Kieran E; Pauza, Audrys G; Pauziene, Neringa; Pauza, Dainius H

2014-01-01

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517–2788; aged) vs. 2118 ± 108 (range 1513–2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans. PMID:24527844

Acute triventricular hydrocephalus caused by choroid plexus cysts: a diagnostic and neurosurgical challenge.

PubMed

Spennato, Pietro; Chiaramonte, Carmela; Cicala, Domenico; Donofrio, Vittoria; Barbarisi, Manlio; Nastro, Anna; Mirone, Giuseppe; Trischitta, Vincenzo; Cinalli, Giuseppe

2016-11-01

OBJECTIVE Intraventricular choroid plexus cysts are unusual causes of acute hydrocephalus in children. Radiological diagnosis of intraventricular choroid plexus cysts is difficult because they have very thin walls and fluid contents similar to CSF and can go undetected on routine CT studies. METHODS This study reports the authors' experience with 5 patients affected by intraventricular cysts originating from the choroid plexus. All patients experienced acute presentation with rapid neurological deterioration, sometimes associated with hypothalamic dysfunction, and required urgent surgery. In 2 cases the symptoms were intermittent, with spontaneous remission and sudden clinical deteriorations, reflecting an intermittent obstruction of the CSF pathway. RESULTS Radiological diagnosis was difficult in these cases because a nonenhanced CT scan revealed only triventricular hydrocephalus, with slight lateral ventricle asymmetry in all cases. MRI with driven-equilibrium sequences and CT ventriculography (in 1 case) allowed the authors to accurately diagnose the intraventricular cysts that typically occupied the posterior part of the third ventricle, occluding the aqueduct and at least 1 foramen of Monro. The patients were managed by urgent implantation of an external ventricular drain in 1 case (followed by endoscopic surgery, after completing a diagnostic workup) and by urgent endoscopic surgery in 4 cases. Endoscopic surgery allowed the shrinkage and near-complete removal of the cysts in all cases. Use of neuronavigation and a laser were indispensable. All procedures were uneventful, resulting in restoration of normal neurological conditions. Long-term follow-up (> 2 years) was available for 2 patients, and no complications or recurrences occurred. CONCLUSIONS This case series emphasizes the necessity of an accurate and precise identification of the possible causes of triventricular hydrocephalus. Endoscopic surgery can be considered the ideal treatment of choroid plexus cysts in children.

Rehabilitation program for children with brachial plexus and peripheral nerve injury.

PubMed

Ramos, L E; Zell, J P

2000-03-01

An aggressive and integrated physical and occupational therapy program is essential in the treatment of congenital brachial plexus injuries and other severe upper extremity nerve injuries. This article addresses the evaluation, identification of needs, establishment of goals, and the approaches to rehabilitation treatment for patients with brachial plexus palsy and other peripheral nerve injuries. Rehabilitative therapy can preserve and build on gains made possible by medical or surgical interventions; however, therapy is vital to these children regardless of whether surgery is indicated. The therapist uses a problem-solving approach to evaluate the patient and select appropriate occupational and physical therapy treatment modalities. Therapy is continually adjusted based on each child's unique needs. An understanding of the therapy principles aids in making appropriate referrals and prescriptions, and helps to coordinate care between the therapist, pediatrician, neurologist, and surgeon.

[Adrenergic innervation of the kidneys in man and various laboratory animals].

PubMed

Shvalev, V N; Chzhao, L Kh

1988-07-01

By means of the neurohistochemical method for slice incubation in 2% solution of glyoxylic acid, innervation of the kidneys of a 57-year-old man after a sudden cardiac death has been investigated, as well as innervation of the kidneys in white rat, rabbit, guinea pig and cat. A rich adrenergic innervation in the organ's blood vessels has been revealed. In particular, adrenergic nervous fibers have been found along the course of afferent glomerular arterioles. Together with innervation of the proximal and distal convoluted tubules, a high density of the terminal adrenergic nervous plexus is revealed along the course of the nephron loops. Adrenergic nervous plexuses of high density are found in the area of the initial part of the urinary excretory pathways and their connection with nervous plexuses of the kidney itself.

Rehabilitation of the Burned Hand

DTIC Science & Technology

2009-01-01

injury in the upper extremity are the shoulder for brachial plexus injuries , the elbow for ulnar nerve lesions, and the wrist for injuries to the ulnar or...median nerves. A brachial plexus injury may result from improper positioning of the shoulder for prolonged periods of time. Shoulder abduction greater...in the early postinjury period as a result of edema, tendon injury , or scar contracture. An immediate consequence of a Rehabilitation Therapies and

Aspergillus osteomyelitis of the lumbar spine complicated with orbital apex syndrome: A potential role of the Batson's plexus in disease propagation.

PubMed

Camargo, Jose F; Seriburi, Vimon; Tenner, Michael; El Khoury, Marc Y

2012-01-01

We report a rare case of orbital apex syndrome following epidural steroid injections of the lumbar spine in an immunocompetent individual with osteomyelitis and discitis caused by Aspergillus fumigatus. We suspect that the craniospinal venous system, also known as the Batson's plexus, was the main route for steroid-facilitated disease propagation from the spine to intracranial structures.

Molecular Targeted Therapies of Childhood Choroid Plexus Carcinoma

DTIC Science & Technology

2013-10-01

Microarray intensities were analyzed in PGS, using the benign human choroid plexus papilloma (CPP) samples as an expression baseline reference. This...additional human and mouse CPC genomic profiles (timeframe: months 1-5). The goal of these studies is to expand our number of genomic profiles (DNA and...mRNA arrays) of both human and mouse CPCs to provide a comprehensive dataset with which to identify key candidate oncogenes, tumor suppressor genes

Molecular Targeted Therapies of Childhood Choroid Plexus Carcinoma

DTIC Science & Technology

2012-10-01

Microarray intensities were analyzed in PGS, using the benign human choroid plexus papilloma (CPP) samples as an expression baseline reference...identify candidate drug targets of CPC. Task 1: Generation of additional human and mouse CPC genomic profiles (timeframe: months 1-5). The goal...of these studies is to expand our number of genomic profiles (DNA and mRNA arrays) of both human and mouse CPCs to provide a comprehensive dataset

Molecular Targeted Therapies of Childhood Choroid Plexus Carcinoma

DTIC Science & Technology

2011-10-01

were analyzed in PGS, using the benign human choroid plexus papilloma (CPP) samples as an expression baseline reference. This analysis highlights...Task 1: Generation of additional human and mouse CPC genomic profiles (timeframe: months 1-5). The goal of these studies is to expand our...number of genomic profiles (DNA and mRNA arrays) of both human and mouse CPCs to provide a comprehensive dataset with which to identify key candidate

Brachial Plexus in the Pampas Fox (Lycalopex gymnocercus): a Descriptive and Comparative Analysis.

PubMed

de Souza Junior, Paulo; da Cruz de Carvalho, Natan; de Mattos, Karine; Abidu Figueiredo, Marcelo; Luiz Quagliatto Santos, André

2017-03-01

Twenty thoracic limbs of ten Lycalopex gymnocercus were dissected to describe origin and distribution of the nerves forming brachial plexuses. The brachial plexus resulted from the connections between the ventral branches of the last three cervical nerves (C6, C7, and C8) and first thoracic nerve (T1). These branches connected the suprascapular, subscapular, axillary, musculocutaneous, radial, median and ulnar nerves to the intrinsic musculature and connected the brachiocephalic, thoracodorsal, lateral thoracic, long thoracic, cranial pectoral and caudal pectoral nerves to the extrinsic musculature. The C7 ventral branches contribute most to the formation of the nerves (62.7%), followed by C8 (58.8%), T1 (40.0%) and C6 (24.6%). Of the 260 nerves dissected, 69.2% resulted from a combination of two or three branches, while only 30.8% originated from a single branch. The origin and innervation area of the pampas fox brachial plexus, in comparison with other domestic and wild species, were most similar to the domestic dog and wild canids from the neotropics. The results of this study can serve as a base for comparative morphofunctional analysis involving this species and development of nerve block techniques. Anat Rec, 300:537-548, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Usefulness of IDEAL T2 imaging for homogeneous fat suppression and reducing susceptibility artefacts in brachial plexus MRI at 3.0 T.

PubMed

Tagliafico, Alberto; Bignotti, Bianca; Tagliafico, Giulio; Martinoli, Carlo

2016-01-01

To quantitatively and qualitatively compare fat-suppressed MR imaging quality using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with that using frequency-selective fat-suppressed (FSFS) T2 images of the brachial plexus at 3.0 T. Prospective MR image analysis was performed in 40 volunteers and 40 patients at a single centre. Oblique-sagittal and coronal IDEAL fat-suppressed T2 images and FSFS T2 images were compared. Visual assessment was performed by two independent musculoskeletal radiologists with respect to: (1) susceptibility artefacts around the neck, (2) homogeneity of fat suppression, (3) image sharpness and (4) tissue resolution contrast of pathologies. The signal-to-noise ratios (SNR) for each image sequence were assessed. Compared to FSFS sequences, IDEAL fat-suppressed T2 images significantly reduced artefacts around the brachial plexus and significantly improved homogeneous fat suppression (p < 0.05). IDEAL significantly improved sharpness and lesion-to-tissue contrast (p < 0.05). The mean SNRs were significantly improved on T2-weighted IDEAL images (p < 0.05). IDEAL technique improved image quality by reducing artefacts around the brachial plexus while maintaining a high SNR and provided superior homogeneous fat suppression than FSFS sequences.

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

PubMed

Gonzalez, Ana Maria; Leadbeater, Wendy; Podvin, Sonia; Borboa, Alexandra; Burg, Michael; Sawada, Ritsuko; Rayner, James; Sims, Karen; Terasaki, Tetsuya; Johanson, Conrad; Stopa, Edward; Eliceiri, Brian; Baird, Andrew

2010-11-04

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Phrenic Nerve Transfer for Reconstruction of Elbow Extension in Severe Brachial Plexus Injuries.

PubMed

Flores, Leandro P; Socolovsky, Mariano

2016-09-01

Background Restoring elbow extension is an important objective to pursue when repairing the brachial plexus in patients with a flail arm. Based upon the good results obtained using the phrenic nerve to restore elbow flexion and shoulder stability, we hypothesized that this nerve could also be employed to reconstruct elbow extension in patients with severe brachial plexus injuries. Methods A retrospective study of 10 patients in which the phrenic nerve targeted the radial nerve (7 patients) or the branch to the long head of the triceps (3 patients) as a surgical strategy for reconstruction of the brachial plexus. Results The mean postoperative follow-up time was 34 months. At final follow-up, elbow extension graded as M4 was measured in three patients, Medical Research Council MRC M3 in five patients, and M2 in one patient, while one patient experienced no measurable recovery (M0). No patient complained or demonstrated any signs of respiratory insufficiency postoperatively. Conclusions The phrenic nerve is a reliable donor for reanimation of elbow extension in such cases, and the branch to the long head of the triceps should be considered as a better target for the nerve transfer. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain

PubMed Central

Anandasabapathy, Niroshana; Victora, Gabriel D.; Meredith, Matthew; Feder, Rachel; Dong, Baojun; Kluger, Courtney; Yao, Kaihui; Dustin, Michael L.; Nussenzweig, Michel C.; Steinman, Ralph M.

2011-01-01

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia. PMID:21788405

Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.

PubMed

Anandasabapathy, Niroshana; Victora, Gabriel D; Meredith, Matthew; Feder, Rachel; Dong, Baojun; Kluger, Courtney; Yao, Kaihui; Dustin, Michael L; Nussenzweig, Michel C; Steinman, Ralph M; Liu, Kang

2011-08-01

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5-7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.

Aspergillus osteomyelitis of the lumbar spine complicated with orbital apex syndrome: A potential role of the Batson's plexus in disease propagation

PubMed Central

Camargo, Jose F.; Seriburi, Vimon; Tenner, Michael; El Khoury, Marc Y.

2012-01-01

We report a rare case of orbital apex syndrome following epidural steroid injections of the lumbar spine in an immunocompetent individual with osteomyelitis and discitis caused by Aspergillus fumigatus. We suspect that the craniospinal venous system, also known as the Batson's plexus, was the main route for steroid-facilitated disease propagation from the spine to intracranial structures. PMID:24371725

Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.

PubMed

Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

2015-01-01

Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD.

Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer’s Disease Patients

PubMed Central

Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

2015-01-01

Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer’s disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood–cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD. PMID:25926771

Diagnosis and treatment of the hemiplegic patient with brachial plexus injury.

PubMed

Meredith, J; Taft, G; Kaplan, P

1981-10-01

Brachial plexus injury was observed as a complication in 5 of 12 hemiplegic patients admitted over a 5-week period to an inpatient unit of the Rehabilitation Institute of Chicago. These patients exhibited unusual patterns of muscle atrophy and return of function in the impaired upper extremity. Occupational therapists may play an important part in the diagnosis and treatment of this complication of hemiplegia by promptly recognizing its subtle clinical signs and instituting appropriate therapy. Electromyography may be recommended to confirm this diagnosis. The treatment of choice is to maintain correct positioning of the limb both day and night, to use facilitation techniques for specific muscles in order to prevent atrophy, and to maintain passive range of motion as much as possible. Prevention of brachial plexus injury depends largely on the education of patient, family, and staff as to the potential hazards to a frail extremity that has no protective responses.

Ultrasound guided therapeutic injections of the cervical spine and brachial plexus.

PubMed

Cormick, Wes

2014-02-01

Introduction : Recent applications in ultrasound imaging include ultrasound assessment and ultrasound guided therapeutic injections of the spine and brachial plexus. Discussion : Ultrasound is an ideal modality for these regions as it allows accurate safe and quick injection of single or multiple sites. It has the added advantages of lack of ionising radiation, and can be done without requiring large expensive radiology equipment. Conclusion : Brachial plexus pathology may be present in patients presenting for shoulder symptoms where very little is found at imaging the shoulder. It is important to understand the anatomy and normal variants that may exist to be able to recognise when pathology is present. When pathology is demonstrated it is easy to do a trial of therapy with ultrasound guided injection of steroid around the nerve lesion. This review will outline the normal anatomy and variants and common pathology, which can be amenable to ultrasound guided injection of steroid.

Noninvasive in vivo optical characterization of blood flow and oxygen consumption in the superficial plexus of skin

NASA Astrophysics Data System (ADS)

Liasi, Faezeh Talebi; Samatham, Ravikant; Jacques, Steven L.

2017-11-01

Assessing the metabolic activity of a tissue, whether normal, damaged, aged, or pathologic, is useful for diagnosis and evaluating the effects of drugs. This report describes a handheld optical fiber probe that contacts the skin, applies pressure to blanch the superficial vascular plexus of the skin, then releases the pressure to allow refill of the plexus. The optical probe uses white light spectroscopy to record the time dynamics of blanching and refilling. The magnitude and dynamics of changes in blood content and hemoglobin oxygen saturation yield an estimate of the oxygen consumption rate (OCR) in units of attomoles per cell per second. The average value of OCR on nine forearm sites on five subjects was 10±5 (amol/cell/s). This low-cost, portable, rapid, noninvasive optical probe can characterize the OCR of a skin site to assess the metabolic activity of the epidermis or a superficial lesion.

Tendon transfer to reconstruct wrist extension in children with obstetric brachial plexus palsy.

PubMed

Al-Qattan, M M

2003-04-01

This study reports on 20 children with obstetric brachial plexus palsy who underwent a tendon transfer to reconstruct wrist extension. The mean age at the time of tendon transfer was 8 years. There were seven patients with Erb's palsy and the remaining 13 had total palsy. The flexor carpi ulnaris was utilized 15 times and the flexor carpi radialis five times. The transferred tendon was sutured to the tendon of the extensor carpi radialis brevis. The result of the transfer was assessed according to a modified Medical Research Council (MRC) muscle grading system. A good result was obtained in 18 patients (modified MRC grade of 4) and a fair result (modified MRC grade of 3) in two. The choice of tendon transfer to reconstruct the wrist drop deformity in various conditions including adult traumatic brachial plexus injuries is discussed.

THE RELATIONSHIP BETWEEN FOVEAL AVASCULAR ZONE AREA, VESSEL DENSITY, AND CYSTOID CHANGES IN DIABETIC RETINOPATHY, AN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY STUDY.

PubMed

Tarassoly, Kia; Miraftabi, Arezoo; Soltan Sanjari, Mostafa; Parvaresh, Mohammad Mehdi

2017-06-29

To measure the foveal avascular zone (FAZ) areas and vessel densities of patients with diabetic retinopathy and to study their relationship with diabetic cystoid changes and retinal thickness. Prospective case series of 51 eyes of 31 patients with diabetic retinopathy. The eyes were grouped based on the presence or absence of cystoid edema and evaluated using optical coherence tomography angiography. The FAZ areas and vessel density were compared. The FAZ area at the superficial capillary plexus level was equal between the eyes with and without cystoid edema. Vessel density did not differ as well. There was no correlation with retinal thickness. In eyes with cystoid changes, FAZ area changes at the deep capillary plexus level were difficult to interpret. The FAZ area and vessel density at the superficial capillary plexus level are reproducible and independent of the presence of cystoid edema.

[Choroid plexus tumors].

PubMed

Pianetti, G; Fonseca, L F

1998-06-01

This analysis comprises 15 children under 16 years of age, with choroid plexus tumors, seen in the Service of Paediatric Neurosurgery, Hospital das Clínicas and Hospital São Francisco de Assis in Belo Horizonte, Brazil, between 1981 and 1996. The patients were aged between 4 months and 16 years (average of 3 years and a half); 10 were less than 2 years, 9 were female; 14 children had clinical evidence of intracranial hypertension. All the children underwent CT scan and the choroid plexus tumors were clearly demonstrated in 14 of then. In 8 children the tumors were located in one lateral ventricle, 5 in the fourth ventricle and 2 had the tumors in more than one ventricle, 11 children required ventriculo-peritoneal shunt; 14 cases were operated on, 13 with total excision; 2 children died, respectively 7 days and one year after the surgery. Pathological examination revealed papillomas in 12 cases and carcinoma in two cases.

Swept-Source Optical Coherence Tomography Angiography in West Nile Virus Chorioretinitis and Associated Occlusive Retinal Vasculitis.

PubMed

Khairallah, Moncef; Kahloun, Rim; Gargouri, Salma; Jelliti, Bechir; Sellami, Dorra; Ben Yahia, Salim; Feki, Jamel

2017-08-01

A 65-year-old man with diabetes and a history of fever of unknown origin 2 weeks earlier complained of sudden decreased vision in the left eye. The patient was diagnosed with bilateral West Nile virus (WNV) chorioretinitis associated with occlusive retinal vasculitis in the left eye. Swept-source optical coherence tomography angiography (SS-OCTA) of the left eye showed extensive, well-delineated, hypointense non-perfusion areas and perifoveal capillary arcade disruption in the superficial capillary plexus, as well as larger non-perfusion areas, capillary rarefaction, and diffuse capillary network attenuation and disorganization in the deep capillary plexus. OCTA may be a valuable tool for noninvasively assessing occlusive retinal vasculitis associated with WNV infection. It allows an accurate detection and precise delineation of areas of retinal capillary nonperfusion in both the superficial and deep capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:672-675.]. Copyright 2017, SLACK Incorporated.

Anatomy and development of the meninges: implications for subdural collections and CSF circulation.

PubMed

Mack, Julie; Squier, Waney; Eastman, James T

2009-03-01

The dura is traditionally viewed as a supportive fibrous covering of the brain containing the dural venous sinuses but otherwise devoid of vessels and lacking any specific function. However, review of the embryology and anatomy reveals the dura to be a complex, vascularized and innervated structure, not a simple fibrous covering. The dura contains an inner vascular plexus that is larger in the infant than in the adult, and this plexus likely plays a role in CSF absorption. This role could be particularly important in the infant whose arachnoid granulations are not completely developed. Although subdural hemorrhage is frequently traumatic, there are nontraumatic conditions associated with subdural hemorrhage, and the inner dural plexus is a likely source of bleeding in these nontraumatic circumstances. This review outlines the development and age-specific vascularity of the dura and offers an alternative perspective on the role of the dura in homeostasis of the central nervous system.

Outcome Following Spinal Accessory to Suprascapular (Spinoscapular) Nerve Transfer in Infants with Brachial Plexus Birth Injuries

PubMed Central

Ruchelsman, David E.; Ramos, Lorna E.; Alfonso, Israel; Price, Andrew E.; Grossman, Agatha

2009-01-01

The purpose of this study is to evaluate the value of distal spinal accessory nerve (SAN) transfer to the suprascapular nerve (SSN) in children with brachial plexus birth injuries in order to better define the application and outcome of this transfer in these infants. Over a 3-year period, 34 infants with brachial plexus injuries underwent transfer of the SAN to the SSN as part of the primary surgical reconstruction. Twenty-five patients (direct repair, n = 20; interposition graft, n = 5) achieved a minimum follow-up of 24 months. Fourteen children underwent plexus reconstruction with SAN-to-SSN transfer at less than 9 months of age, and 11 underwent surgical reconstruction at the age of 9 months or older. Mean age at the time of nerve transfer was 11.6 months (range, 5–30 months). At latest follow-up, active shoulder external rotation was measured in the arm abducted position and confirmed by review of videos. The Gilbert and Miami shoulder classification scores were utilized to report shoulder-specific functional outcomes. The effects of patient age at the time of nerve transfer and the use of interpositional nerve graft were analyzed. Overall mean active external rotation measured 69.6°; mean Gilbert score was 4.1 and the mean Miami score was 7.1, corresponding to overall good shoulder functional outcomes. Similar clinical and shoulder-specific functional outcomes were obtained in patients undergoing early (<9 months of age, n = 14) and late (>9 months of age, n = 11) SAN-to-SSN transfer and primary plexus reconstruction. Nine patients (27%) were lost to follow-up and are not included in the analysis. Optimum results were achieved following direct transfer (n = 20). Results following the use of an interpositional graft (n = 5) were rated satisfactory. No patient required a secondary shoulder procedure during the study period. There were no postoperative complications. Distal SAN-to-SSN (spinoscapular) nerve transfer is a reliable option for shoulder reinnervation in infants with brachial plexus birth injuries. Direct transfer seems to be the optimum method. The age of the patient does not seem to significantly impact on outcome. PMID:19882190

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation.

PubMed

Achariyar, Thiyagaragan M; Li, Baoman; Peng, Weiguo; Verghese, Philip B; Shi, Yang; McConnell, Evan; Benraiss, Abdellatif; Kasper, Tristan; Song, Wei; Takano, Takahiro; Holtzman, David M; Nedergaard, Maiken; Deane, Rashid

2016-12-08

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models.

PubMed

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-10-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes' bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in MATLAB. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the average temperature in the prostate and neurovascular bundles could be cooled down to 25 °C within 30 min. For cases with abundant venous plexus and large prostate, the temperature could not reach 25 °C at the end of 3 h cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models

PubMed Central

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T.; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-01-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes’ bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in Matlab. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the averaged temperature in the prostate and neurovascular bundles could be cooled down to 25°C within 30 minutes. For cases with abundant venous plexus and large prostate, the temperature could not reach 25°C at the end of 3 hours cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. PMID:26198131

Cannabinoid-1 (CB1) receptors regulate colonic propulsion by acting at motor neurons within the ascending motor pathways in mouse colon.

PubMed

Sibaev, Andrei; Yüce, Birol; Kemmer, Markus; Van Nassauw, Luc; Broedl, Ulli; Allescher, Hans D; Göke, Burkhard; Timmermans, Jean-Pierre; Storr, Martin

2009-01-01

Cannabinoid-1 (CB(1)) receptors on myenteric neurons are involved in the regulation of intestinal motility. Our aim was to investigate CB(1) receptor involvement in ascending neurotransmission in mouse colon and to characterize the involved structures by functional and morphological means. Presence of the CB(1) receptor was investigated by RT-PCR, and immunohistochemistry was used for colabeling studies. Myenteric reflex responses were initiated by electrical stimulation (ES) at different distances, and junction potentials (JP) were recorded from circular smooth muscle cells by intracellular recording in an unpartitioned and a partitioned recording chamber. In vivo colonic propulsion was tested in wild-type and CB(1)(-/-) mice. Immunostaining with the cytoskeletal marker peripherin showed CB(1) immunoreactivity both on Dogiel type I and type II neurons. Further neurochemical characterization revealed CB(1) on choline acetyltransferase-, calretinin-, and 5-HT-immunopositive myenteric neurons, but nitrergic neurons appeared immunonegative for CB(1) immunostaining. Solitary spindle-shaped CB(1)-immunoreactive cells in between smooth muscle cells lacked specific markers for interstitial cells of Cajal or glial cells. ES elicited neuronally mediated excitatory JP (EJP) and inhibitory JP. Gradual increases in distance resulted in a wave-like EJP with EJP amplitudes being maximal at the location of stimulating electrode 6 and a maximal EJP projection distance of approximately 18 mm. The CB(1) receptor agonist WIN 55,212-2 reduced the amplitude of EJP and was responsible for shortening the oral spreading of the excitatory impulse. In a partitioned chamber, WIN 55,212-2 reduced EJP at the separated oral sites, proving that CB(1) activation inhibits interneuron-mediated neurotransmission. These effects were absent in the presence of the CB(1) antagonist SR141716A, which, when given alone, had no effect. WIN 55,212-2 inhibited colonic propulsion in wild-type mice but not in SR141716A-pretreated wild-type or CB(1)(-/-) mice. Activation of the CB(1) receptor modulates excitatory cholinergic neurotransmission in mouse colon by reducing amplitude and spatial spreading of the ascending electrophysiological impulses. This effect on electrophysiological spreading involves CB(1)-mediated effects on motor neurons and ascending interneurons and is likely to underlie the here reported in vivo reduction in colonic propulsion.

United States v. Kubrick: Scope and Application

DTIC Science & Technology

1987-04-01

clavicles were broken, the injury to the brachial plexus was a separate injury . The Burgesses did not discover this injury until they were told about...of injury , was not applied. 106 Just as the Stoleson court noted defendants’ occupations should not control when a claim accrues, the presence of...canal. The fracture caused Erb’s Palsy, a paralysis of the muscles of the upper arm, because the fracture injured his right brachial plexus , a nerve

Watson-Jones Lecture, 1976. Some lesions of the brachial plexus.

PubMed Central

Bonney, G.

1977-01-01

Three types of lesion of the brachial plexus are discussed: entrapment syndrome; tumours; and traumatic lesions. In the first the importance of the pathological anatomy is stressed; in the second the rewarding results of accurate diagnosis and careful treatment are noted; and in the third the expanding possibilities of neural reconstruction and of specific treatment for pain are described. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 8 Fig. 9 Fig. 10 PMID:879635

Distinct Retinal Capillary Plexuses in Normal Eyes as Observed in Optical Coherence Tomography Angiography Axial Profile Analysis.

PubMed

Hirano, Takao; Chanwimol, Karntida; Weichsel, Julian; Tepelus, Tudor; Sadda, Srinivas

2018-06-20

Optical coherence tomography angiography (OCTA) allows the retinal microvasculature to be visualized at various retinal depths. Previous studies introduced OCTA axial profile analysis and showed regional variations in the number and location of axially distinct vascular retinal plexuses. OCTA acquisition and processing approaches, however, vary in terms of their resulting transverse and axial resolutions, and especially the latter could potentially influence the profile analysis results. Our study imaged normal eyes using the Spectralis OCT2 with a full-spectrum, probabilistic OCTA algorithm, that, in marked contrast to split-spectrum approaches, preserves the original high OCT axial resolution also within the resulting OCTA signal. En face OCTA images are generally created by averaging flow signals over a finite axial depth window. However, we assessed regional OCTA signal profiles at each depth position at full axial resolution. All regions had two sharp vessel density peaks near the inner and outer boundaries of the inner nuclear layer, indicating separate intermediate and deep capillary plexuses. The superficial vascular plexus (SVP) separated into two distinct peaks within the ganglion cell layer in the parafoveal zone. The nasal, superior, and inferior perifovea had a deeper SVP peak that was shifted anteriorly compared to the parafoveal zone. Axial vascular density analysis with high-resolution, full spectrum OCTA thus allows healthy retinal vasculature to be precisely reconstructed and may be useful for clinically assessing retinal pathology.

Neonatal brachial plexus palsy--management and prognostic factors.

PubMed

Yang, Lynda J-S

2014-06-01

Successful treatment of patients with neonatal brachial plexus palsy (NBPP) begins with a thorough understanding of the anatomy of the brachial plexus and of the pathophysiology of nerve injury via which the brachial plexus nerves stretched in the perinatal period manifest as a weak or paralyzed upper extremity in the newborn. NBPP can be classified by systems that can guide the prognosis and the management as these systems are based on the extent and severity of nerve injury, anatomy of nerve injury, and clinical presentation. Serial physical examinations, supplemented by a thorough maternal and perinatal history, are critical to the formulation of the treatment plan that relies upon occupational/physical therapy and rehabilitation management but may include nerve reconstruction and secondary musculoskeletal surgeries. Adjunctive imaging and electrodiagnostic studies provide additional information to guide prognosis and treatment. As research improves not only the technical aspects of NBPP treatment but also the ability to assess the activity and participation as well as body structure and function of NBPP patients, the functional outcomes for affected infants have an overall optimistic prognosis, with the majority recovering adequate functional use of the affected arm. Of importance are (i) early referral to interdisciplinary specialty clinics that can provide up-to-date advances in clinical care and (ii) increasing research/awareness of the psychosocial and patient-reported quality-of-life issues that surround the chronic disablement of NBPP. Copyright © 2014 Elsevier Inc. All rights reserved.

Serotonergic neuron system in the spinal cord of the gar Lepisosteus oculatus (Lepisosteiformes, Osteichthyes) with special regard to the juxtameningeal serotonergic plexus as a paracrine site.

PubMed

Chiba, Akira

2007-02-08

Immunohistochemical and electron microscopic studies were carried out to elucidate the structure of the serotonergic neuron system in the spinal cord of the spotted gar, Lepisosteus oculatus, a nonteleost actinopterygian. Serotonin-immunoreactive (5HT-IR) cell bodies and fibers were widely distributed in the spinal cord, constituting an intrinsic neuron system. This system comprised three anatomical cell groups in different portions of the spinal cord, i.e., the rostromedial cell group, the paired ventrolateral cell groups, and the ventral superficial cell group. The rostromedial cell group included cerebrospinal fluid-contacting neurons with intraventricular processes. The immunostained fibers projecting from all three of these cell groups ran in various directions, mainly ventrally and ventrolaterally, and partly gave rise to a dense plexus at the ventrolateral surface of the spinal cord. Immunoelectron microscopy of the relevant portion demonstrated many varicose fibers containing 5HT-immunopositive vesicles. Conventional electron microscopy of the plexus showed that the constituent varicose fibers were unmyelinated and frequently made a direct contact with the basement membrane contiguous to the leptomeniges (meninx primitiva). There, exocytotic figures of cytoplasmic vesicles were demonstrated, suggesting that 5HT may be secreted, in a paracrine way, into the extraspinal space. This specialized area in the gar spinal cord may be referred to as the juxtameningeal serotonergic plexus.

Connecting the coronaries: How the coronary plexus develops and is functionalized

PubMed Central

Dyer, Laura; Pi, Xinchun; Patterson, Cam

2015-01-01

The establishment of the coronary circulation is one of the final critical steps during heart development. Despite decades of research, our understanding of how the coronary vasculature develops and connects to the aorta remains limited. This review serves two specific purposes: it addresses recent advances in understanding the origin of the coronary endothelium, and it then focuses on the last crucial step of coronary vasculature development, the connection of the coronary plexus to the aorta. The chick and quail animal models have yielded most of the information for how these connections form, starting with a fine network of vessels that penetrate the aorta and coalesce to form two distinct ostia. Studies in mouse and rat confirm that at least some of these steps are conserved in mammals, but gaps still exist in our understanding of mammalian coronary ostia formation. The signaling cues necessary to guide the coronary plexus to the aorta are also incompletely understood. Hypoxia-inducible transcription factor-1 and its downstream targets are among the few identified genes that promote the formation of the coronary stems. Together, this review summarizes our current knowledge of coronary vascular formation and highlights the significant gaps that remain. In addition, it highlights some of the coronary artery anomalies known to affect human health, demonstrating that even seemingly subtle defects arising from incorrect coronary plexus formation can result in significant health crises. PMID:25173872

Comparing the Efficacy of Triple Nerve Transfers with Nerve Graft Reconstruction in Upper Trunk Obstetric Brachial Plexus Injury.

PubMed

O'Grady, Kathleen M; Power, Hollie A; Olson, Jaret L; Morhart, Michael J; Harrop, A Robertson; Watt, M Joe; Chan, K Ming

2017-10-01

Upper trunk obstetric brachial plexus injury can cause profound shoulder and elbow dysfunction. Although neuroma excision with interpositional sural nerve grafting is the current gold standard, distal nerve transfers have a number of potential advantages. The goal of this study was to compare the clinical outcomes and health care costs between nerve grafting and distal nerve transfers in children with upper trunk obstetric brachial plexus injury. In this prospective cohort study, children who underwent triple nerve transfers were followed with the Active Movement Scale for 2 years. Their outcomes were compared to those of children who underwent nerve graft reconstruction. To assess health care use, a cost analysis was also performed. Twelve patients who underwent nerve grafting were compared to 14 patients who underwent triple nerve transfers. Both groups had similar baseline characteristics and showed improved shoulder and elbow function following surgery. However, the nerve transfer group displayed significantly greater improvement in shoulder external rotation and forearm supination 2 years after surgery (p < 0.05). The operative time and length of hospital stay were significantly lower (p < 0.05), and the overall cost was approximately 50 percent less in the nerve transfer group. Triple nerve transfer for upper trunk obstetric brachial plexus injury is a feasible option, with better functional shoulder external rotation and forearm supination, faster recovery, and lower cost compared with traditional nerve graft reconstruction. Therapeutic, II.

Distal nerve transfer versus supraclavicular nerve grafting: comparison of elbow flexion outcome in neonatal brachial plexus palsy with C5-C7 involvement.

PubMed

Heise, Carlos O; Siqueira, Mario G; Martins, Roberto S; Foroni, Luciano H; Sterman-Neto, Hugo

2017-09-01

Ulnar and median nerve transfers to arm muscles have been used to recover elbow flexion in infants with neonatal brachial plexus palsy, but there is no direct outcome comparison with the classical supraclavicular nerve grafting approach. We retrospectively analyzed patients with C5-C7 neonatal brachial plexus palsy submitted to nerve surgery and recorded elbow flexion recovery using the active movement scale (0-7) at 12 and 24 months after surgery. We compared 13 patients submitted to supraclavicular nerve grafting with 21 patients submitted to distal ulnar or median nerve transfer to biceps motor branch. We considered elbow flexion scores of 6 or 7 as good results. The mean elbow flexion score and the proportion of good results were better using distal nerve transfers than supraclavicular grafting at 12 months (p < 0.01), but not at 24 months. Two patients with failed supraclavicular nerve grafting at 12 months showed good elbow flexion recovery after ulnar nerve transfers. Distal nerve transfers provided faster elbow flexion recovery than supraclavicular nerve grafting, but there was no significant difference in the outcome after 24 months of surgery. Patients with failed supraclavicular grafting operated early can still benefit from late distal nerve transfers. Supraclavicular nerve grafting should remain as the first line surgical treatment for children with neonatal brachial plexus palsy.

[Pattern of paralysis and reconstructive operations after traumatic brachial plexus lesions].

PubMed

Rühmann, O; Schmolke, S; Carls, J; Wirth, C J

2002-12-01

The aim of this study was to evaluate persistent patterns of paralysis after traumatic brachial plexus lesions. As a result, consecutive reconstructive operations according to our differential therapy concept are presented. Between 04/1994 and 12/2000 in 104 patients with brachial plexus palsy, the grade of muscle power of the affected upper extremities was evaluated prospectively. The neuromuscular patterns of defect showed, in most cases, insufficient muscle power grades of 0-2 for the deltoid muscle (90%), supraspinatus muscle (82%), infraspinatus muscle (93%), elbow flexors (67% to 77%), hand and finger extensors (69% to 71%), and the abductor and extensors of the thumb (67% to 70%). In corresponding frequency, the following operations were performed between 04/1994 and 06/2002: shoulder arthrodesis (n 26), trapezius transfer (n 80), rotation osteotomy of humerus (n 10), triceps to biceps transposition (n 11), transposition of forearm flexors or extensors/Steindler operation (n 12), latissimus transfer (n 7), pectoralis transfer (n 1), teres major transfer (n 1), transposition of forearm flexors to the tendons of extensor digitorum (n 19) and of the extensor pollicis longus (n 9), and wrist arthrodesis (n 5). On malfunction of muscles following brachial plexus lesions, taking into account the individual neuromuscular defect, passive joint function, and bony deformities, different procedures such as muscle transposition, arthrodesis, and corrective osteotomy can be performed to improve function of the upper extremity.

Presence of time-dependent diffusion in the brachial plexus.

PubMed

Mahbub, Zaid B; Peters, Andrew M; Gowland, Penny A

2018-02-01

This work describes the development of a method to measure the variation of apparent diffusion coefficient (ADC) with diffusion time (Δ) in the brachial plexus, as a potential method of probing microstructure. Diffusion-weighted MRI with body signal suppression was used to highlight the nerves from surrounding tissues, and sequence parameters were optimized for sensitivity to change with diffusion time. A porous media-restricted diffusion model based on the Latour-Mitra equation was fitted to the diffusion time-dependent ADC data from the brachial plexus nerves and cord. The ADC was observed to reduce at long diffusion times, confirming that diffusion was restricted in the nerves and cord in healthy subjects. T2 of the nerves was measured to be 80 ± 5 ms, the diffusion coefficient was found to vary from (1.5 ± 0.1) × 10 -3 mm 2 /s at a diffusion time of 18.3 ms to (1.0 ± 0.2) × 10 -3 mm 2 /s at a diffusion time of 81.3 ms. A novel method of probing restricted diffusion in the brachial plexus was developed. Resulting parameters were comparable with values obtained previously on biological systems. Magn Reson Med 79:789-795, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Distribution of vesicular glutamate transporter 1 (VGLUT1) in the mouse esophagus.

PubMed

Kraus, T; Neuhuber, W L; Raab, M

2007-08-01

In rat and mouse esophagus, vesicular glutamate transporter 2 (VGLUT2) has been demonstrated to identify vagal intraganglionic laminar endings (IGLEs); this has recently also been shown for VGLUT1 in rat esophagus. In this study, we have investigated the distribution of VGLUT1 in the mouse esophagus and compared these results with the recently published data from the rat esophagus. Unexpectedly, we have discovered that VGLUT1 mostly fails to identify IGLEs in the mouse esophagus. This is surprising, since the distribution of VGLUT2 shows comparable results in both species. Confocal imaging has revealed substantial colocalization of VGLUT1 immunoreactivity (-ir) with cholinergic and nitrergic/peptidergic markers within the myenteric neuropil and in both cholinergic and nitrergic myenteric neuronal cell bodies. VGLUT1 and cholinergic markers have also been colocalized in fibers of the muscularis mucosae, whereas VGLUT1 and nitrergic markers have never been colocalized in fibers of the muscularis mucosae, although this does occur in fibers of the muscularis running to motor endplates. Thus, VGLUT1 is contained in the nitrergic innervation of mouse esophageal motor endplates, another difference from the rat esophagus. VGLUT1-ir is therefore present in extrinsic and intrinsic innervation of the mouse esophagus, but the significant differences from the rat indicate species variations concerning the distribution of VGLUTs in the peripheral nervous system.

A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

PubMed

Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

2017-09-23

Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P < 0.0001), female gender (P = 0.022), increased age (P = 0.048), and increased local anesthetic dose (P = 0.01). In a multivariable model, block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Cellular Specificity of the Blood–CSF Barrier for Albumin Transfer across the Choroid Plexus Epithelium

PubMed Central

Liddelow, Shane A.; Dzięgielewska, Katarzyna M.; Møllgård, Kjeld; Whish, Sophie C.; Noor, Natassya M.; Wheaton, Benjamin J.; Gehwolf, Renate; Wagner, Andrea; Traweger, Andreas; Bauer, Hannelore; Bauer, Hans-Christian; Saunders, Norman R.

2014-01-01

To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood–CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood–CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells. PMID:25211495

Tolerance of the Brachial Plexus to High-Dose Reirradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.

Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculatedmore » by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.« less

Patterns of blood supply to the gastric mucosa. A comparative study revealing an end-artery model.

PubMed Central

Piasecki, C; Wyatt, C

1986-01-01

The form of the gastric arterial supply to the mucosa has been studied in dog, swine, ferret, cat, guinea-pig, rabbit and rhesus monkey. In all these species, the bore of vessels in the submucous plexus diminished from body to pylorus, though this was most marked in the guinea-pig and rabbit. The plexus was also continuous across the pylorus with duodenal vessels. Thus the well known poverty of vascularity in distal parts of the human stomach is shared by other species and is unlikely to be a contributory factor to the initiation of peptic ulcer, a disease limited to man. In dog, swine, ferret and cat, as in man, the primary (largest) and secondary (smaller) components of the plexus lay entirely in the submucosa. In the cat, there was a secondary plexus of much smaller vessels deep to the muscularis mucosae. In the guinea-pig, rat, rabbit and monkey, both plexuses were mostly embedded within the muscularis mucosae. As a result, mucosal arteries had two modes of origin: (a) the first, in which they did not pass through the muscularis mucosae as exemplified in the cat, and (b) the second, where they did pass through muscularis mucosae as exemplified by the dog, ferret and swine; in other species, they passed through part of the muscularis mucosae. Areas of mucosa supplied by a single mucosal artery were measured, and ranged widely from the smallest in the cat to the largest in the dog. These features do not seem to have been reported previously, and may be associated with as yet undiscovered functional mechanisms of the muscularis mucosae. Mucosal arteries of extramural origin were found to occur occasionally in the guinea-pig and rabbit, and hence these may provide an experimental model of the pattern existing in man. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:3693108

Pain and brachial plexus lesions: evaluation of initial outcomes after reconstructive microsurgery and validation of a new pain severity scale.

PubMed

Bonilla, Gonzalo; Di Masi, Gilda; Battaglia, Danilo; Otero, José María; Socolovsky, Mariano

2011-01-01

Peripheral nerve lesions usually are associated with neuropathic pain. In the present paper, we describe a simple scale to quantify pain after brachial plexus injuries and apply this scale to a series of patients to determine initial outcomes after reconstructive surgery. Fifty-one patients with traumatic brachial plexus avulsion injuries were treated over the period of one calendar year at one center by the same surgical team. Of these, 28 patients who were available for follow-up reported some degree of neuropathic pain radiating towards the hand or forearm and underwent reconstructive microsurgery and direct pain management, including trunk and nerve neurolysis and repair. A special pain severity rating scale was developed and used to assess patients' pain before and after surgery, over a minimum follow-up of 6 months. An independent researcher, not part of the surgical team, performed all pre- and postoperative evaluations. Of the 28 patients with brachial plexus traction injuries who met eligibility criteria, 93% were male, and most were young (mean age, 27.6 years). The mean preoperative severity of pain using our scale was 30.9 out of a maximum of 37 (± 0.76 SD), which fell to a mean of 6.9 (± 0.68 SD) 6 months post-procedure. On average, pain declined by 78% across the whole series, a decline that was statistically significant (p < .001). Subset analysis revealed similar improvements across all the different parameters of pain. We have designed and tested a simple and reliable method by which to quantify neuropathic pain after traumatic brachial plexus injuries. Initial surgical treatment of the paralysis--including nerve, trunk and root reconstruction, and neurolysis--comprises an effective means by which to initially treat neuropathic pain. Ablative or neuromodulative procedures, like dorsal root entry zone, should be reserved for refractory cases.

Functional interdependence of neurons in a single canine intrinsic cardiac ganglionated plexus

PubMed Central

Thompson, G W; Collier, K; Ardell, J L; Kember, G; Armour, J A

2000-01-01

To determine the activity characteristics displayed by different subpopulations of neurons in a single intrinsic cardiac ganglionated plexus, the behaviour and co-ordination of activity generated by neurons in two loci of the right atrial ganglionated plexus (RAGP) were evaluated in 16 anaesthetized dogs during basal states as well as in response to increasing inputs from ventricular sensory neurites. These sub-populations of right atrial neurons received afferent inputs from sensory neurites in both ventricles that were responsive to local mechanical stimuli and the nitric oxide donor nitroprusside. Neurons in at least one RAGP locus were activated by epicardial application of veratridine, bradykinin, the β1-adrenoceptor agonist prenaterol or glutamate. Epicardial application of angiotensin II, the selective β2-adrenoceptor agonist terbutaline and selective α-adrenoceptor agonists elicited inconsistent neuronal responses. The activity generated by both populations of atrial neurons studied over 5 min periods during basal states displayed periodic coupled behaviour (cross-correlation coefficients of activities that reached, on average, 0·88 ± 0·03; range 0·71–1) for 15–30 s periods of time. These periods of coupled activity occurred every 30–50 s during basal states, as well as when neuronal activity was enhanced by chemical activation of their ventricular sensory inputs. These results indicate that neurons throughout one intrinsic cardiac ganglionated plexus receive inputs from mechano- and chemosensory neurites located in both ventricles. That such neurons respond to multiple chemical stimuli, including those liberated from adjacent adrenergic efferent nerve terminals, indicates the complexity of the integrative processing of information that occurs within the intrinsic cardiac nervous system. It is proposed that the interdependent activity displayed by populations of neurons in different regions of one intrinsic cardiac ganglionated plexus, responding as they do to multiple cardiac sensory inputs, forms the basis for integrated regional cardiac control. PMID:11060132

A case study from a nursing and occupational therapy perspective - Providing care for a patient with a traumatic brachial plexus injury.

PubMed

Wellington, Beverley; McGeehan, Claire

2015-02-01

This paper presents a case study that demonstrates how collaborative working between professionals enhanced the holistic care for a patient following a traumatic brachial plexus injury. The paper will describe the patient's journey of care from initial presentation, diagnosis and assessment, acute care provision, discharge & rehabilitation to ongoing supportive counselling. The care encompasses input from both a nursing and occupational therapy perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrasound diagnosis of central nervous system anomalies (bifid choroid plexus, ventriculomegaly, Dandy-Walker malformation) associated with multicystic dysplastic kidney disease in a trisomy 9 fetus: case report with literature review.

PubMed

Tonni, Gabriele; Grisolia, Giampaolo

2013-09-01

Trisomy 9 is a lethal chromosomal abnormality that rarely progresses beyond the second trimester of pregnancy. Multiple central nervous system anomalies, including bifid choroid plexus, ventriculomegaly, and Dandy-Walker malformation, associated with multicystic dysplastic kidney disease in a trisomy 9 fetus are reported. The prenatal ultrasound diagnosis has been aided by novel three-dimensional ultrasound software. Copyright © 2012 Wiley Periodicals, Inc.

The Blood Volume of the Guinea Pig: Effects of Epinephrine and Isoproterenol upon the Red Cell and Plasma Volumes, Heart Rate, and Mean Arterial Pressure,

DTIC Science & Technology

1987-09-01

capillaries (4), blood volumes calculated from plasma volume measures must correct for label that has left the system between the time of the injected dose...Splenic sequestration and contraction are mediated by the autonomic nervous system and blood-borne agents (10). Sympathetic nerve fibers from the truncus...sympathlcus and parasympathetic neurons of the nervus vagus (cranial nerve X) innervate the celiac plexus (8, 11). A subdivision of the celiac plexus

Chronic intestinal pseudo-obstruction in a child with Treacher Collins syndrome.

PubMed

Giabicani, E; Lemale, J; Dainese, L; Boudjemaa, S; Coulomb, A; Tounian, P; Dubern, B

2017-10-01

Treacher Collins syndrome (TCS) mainly presents with severe craniofacial developmental abnormalities characterized by a combination of bilateral downward-slanting palpebral fissures, colobomas of the lower eyelids, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. It is due to mutations in Treacher Collins syndrome 1 (TCOF1) (5q32-q33.1) and Polymerase RNA 1 polypeptides D and C (POLR1D [13q12.2], and POLR1C [6p21.1]) genes, which are responsible for increased neuroepithelial apoptosis during embryogenesis resulting in the lack of neural crest cells involved in facial bone and cartilage formation. Altered function of the upper digestive tract has been reported, whereas severe dysmotility disorders have never been reported. We describe here the first case of TCS associated with histologically proven chronic intestinal pseudo-obstruction (CIPO) in humans. Case presentatios A 12-year-old boy with TCS due to TCOF1 gene deletion experienced nutritional difficulties and digestive intolerance from birth. CIPO was suspected during childhood because of severe intestinal dysmotility leading to enteral-jejunal nutrition intolerance and dependence on total parenteral nutrition. Diagnosis of CIPO with nervous abnormalities was histologically confirmed on a surgical rectal biopsy that showed enlarged ganglionic myenteric plexus. At the age of 9 years, an isolated colonic stenosis without dilatation responsible for severe abdominal pain and altered quality of life led to digestive derivation contributing to rapid disappearance of chronic abdominal pain. At the age of 12 years, the patient was still dependent on total home parenteral nutrition 7 days a week to maintain regular growth velocity. Recently, mice studies have pointed out the role played by TCOF1 in ganglionic cell migration in the foregut, suggesting that the synergistic haploinsufficiency of Tcof1 and Pax3, a transcription factor regulating the RET gene involved in disorders of neural crest cell development, probably results in colonic aganglionosis and may explain the association described here between TCS and CIPO. This case may correspond to this possible mechanism in humans. These findings and our clinical report suggest that CIPO may be assessed as unusual digestive manifestations in TCS with TCOF1 deletion. Copyright © 2017. Published by Elsevier SAS.

Muscarinic acetylcholine receptor expression in aganglionic bowel.

PubMed

Oue, T; Yoneda, A; Shima, H; Puri, P

2000-01-01

In Hirschsprung's disease (HD) there exists an overabundance of acetylcholine (ACh), which in turn stimulates excessive production of the enzyme acetylcholinesterase. Muscarinic ACh receptors (mAChRs) play an important role in smooth-muscle contraction. Recent studies have indicated five different subtypes of mAChRs encoded by five different genes, ml to m5. The purpose of this study was to investigate the expression of each mAChR subtype in aganglionic (AG) colon to further understand the pathophysiology of HD. Entire colon resected at the time of pull-through operation for HD was obtained from 14 patients. Specimens obtained at autopsy from 8 age-matched patients without gastrointestinal disease acted as controls. Frozen sections were used for indirect immunohistochemistry as well as in-situ hybridization. Immunohistochemistry was performed using specific antiserum against each mAChR subtype and in-situ hybridization was performed using specific oligonucleotide probes against ml to m5 subtypes. Messenger RNA (mRNA) was extracted from normoganglionic (NG) and AG bowel of HD patients and normal control bowel. Reverse transcription-polymerase chain reaction was performed to evaluate mRNA levels of each mAChR subtype. To adjust the levels of mRNA expression, a housekeeping gene G3PDH, known to be expressed normally, was used as an internal control. Strong m2 and m3 immunoreactivity was observed in the mucosal layer, smooth-muscle layers, and myenteric plexus of NG bowel, whereas ml immunoreactivity was only detected in the mucosal layer. The most striking finding was the abundance of m3-immunoreactive fibers in muscle layers of NG bowel while there was a total lack of m3 fibers in smooth-muscle of AG bowel. Intense mRNA signals encoding m2 and m3 and to a lesser degree ml were detected in NG bowel, and these signals were weak in AG bowel. Immunoreactivity and mRNA expression of m4 and m5 was not detected in NG or AG bowel. The lack of m3-immunoreactive fibers in the smooth-muscle layers of AG bowel and decreased m2 and m3 mRNA expression in AG bowel may be responsible for the motility dysfunction in the aganglionic segment.

Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis.

PubMed

Stavely, Rhian; Robinson, Ainsley M; Miller, Sarah; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

2015-12-30

The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation. MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10(6) cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry. Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro. This study is the first evaluating the functional capacity of guinea pig bone marrow and adipose tissue-derived MSCs and providing evidence of their neuroprotective value in an animal model of colitis. In vitro characteristics of MSCs cannot be extrapolated to their therapeutic efficacy. TGF-β1 released by both types of MSCs might have contributed to the attenuation of enteric neuropathy associated with colitis.

Scapular instability associated with brachial plexus irritation: a proposed causative relationship with treatment implications.

PubMed

Langley, P

1997-01-01

Brachial plexus irritation and other compression neuropathies can be diverse in their presentations and can cause a myriad of signs and symptoms. The purpose of this paper is to review the pertinent anatomy, kinesiology, and neurophysiology and to outline one possible cascade of events that may contribute to more diffuse upper extremity symptoms. Scapular instability and local myofascial trigger points resulting in possible secondary muscle imbalances are described. Their possible relationship to brachial plexus irritation in addition to the implications of the irritation are also discussed. The author postulates that proximal nerve irritation in the region of the thoracic outlet and shoulder may help to account for diffuse or unrelieved symptoms following conventional treatment of distal extremity problems in patients with occupational or cumulative trauma disorders. This paper outlines specific examination procedures for the therapist, which include upper limb tension testing, extensibility testing of the pectoralis minor, and gross manual muscle testing of the lower trapezius.

Nerve compression injuries due to traumatic false aneurysm.

PubMed Central

Robbs, J V; Naidoo, K S

1984-01-01

Experience with 17 patients with delayed onset of compression neuropraxia due to hemorrhage following nonoperative treatment of penetrating arterial injuries is presented. Fifteen cases involved the arteries of the neck shoulder girdle and upper extremity and two the gluteal vessels. This resulted in dysfunction of components of the brachial plexus, median ulnar, and sciatic nerves. Follow-up extended from 3 to 18 months. Of 10 brachial plexus lesions two recovered fully, five partially, and three not at all. Of seven peripheral nerve injuries, full recovery occurred in two patients and none in five. Adverse prognostic factors for neurological recovery are sepsis, involvement of intrinsic hand innervation and the sciatic nerve. An improved prognosis may be expected for upper trunk lesions of the brachial plexus and radial nerve lesions. The complication is essentially avoidable and a careful appraisal of the circulatory status must be made in all patients with penetrating trauma in the neck and shoulder girdle and buttock. PMID:6732331

YAG laser in the treatment of hemorrhoids: a report of 700 cases

NASA Astrophysics Data System (ADS)

Liu, Jian-xun; Zhang, Xinrong

1993-03-01

The results of treating hemorrhoids in 700 cases with a YAG laser knife is reported. Since 1988, the author introduced the YAG laser into the treatment of various kinds of hemorrhoids. The satisfactory results were achieved with 100% cure rate. Some related problems also are discussed in this paper. Hemorrhoid is a kind of common disease. It usually appears in the superior or inferior rectal venous plexus covered with mucosa. The hemorrhoids are divided into internal, external, and mixed types according to their location and origination. The internal hemorrhoid is superior to the dentate line and caused by varicosity of superior rectal venous plexus covered with mucosa, the most common presentation is a bleeding and prolapse mass out of the anus. The external hemorrhoid arises from varicosity of inferior rectal venous plexus, the most important clinical finding is a painful mass covered with skin of the anal canal. The characteristics of mixed type are the combination of the two types as mentioned above.

Combined Sciatic and Lumbar Plexus Nerve Blocks for the Analgesic Management of Hip Arthroscopy Procedures: A Retrospective Review.

PubMed

Jaffe, J Douglas; Morgan, Theodore Ross; Russell, Gregory B

2017-06-01

Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite its minimally invasive nature, there can still be significant reported pain following these procedures. The impact of combined sciatic and lumbar plexus nerve blocks on postoperative pain scores and opioid consumption in patients undergoing hip arthroscopy was investigated. A retrospective analysis of 176 patients revealed that compared with patients with no preoperative peripheral nerve block, significant reductions in pain scores to 24 hours were reported and decreased opioid consumption during the post anesthesia care unit (PACU) stay was recorded; no significant differences in opioid consumption out to 24 hours were discovered. A subgroup analysis comparing two approaches to the sciatic nerve block in patients receiving the additional lumbar plexus nerve block failed to reveal a significant difference for this patient population. We conclude that peripheral nerve blockade can be a useful analgesic modality for patients undergoing hip arthroscopy.

Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach.

PubMed

Yang, Chaoqun; Xu, Jianguang; Chen, Jie; Li, Shulin; Cao, Yu; Zhu, Yi; Xu, Lei

2017-08-01

We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs). The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively. Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals. Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.

Real-time three-dimensional ultrasound-assisted axillary plexus block defines soft tissue planes.

PubMed

Clendenen, Steven R; Riutort, Kevin; Ladlie, Beth L; Robards, Christopher; Franco, Carlo D; Greengrass, Roy A

2009-04-01

Two-dimensional (2D) ultrasound is commonly used for regional block of the axillary brachial plexus. In this technical case report, we described a real-time three-dimensional (3D) ultrasound-guided axillary block. The difference between 2D and 3D ultrasound is similar to the difference between plain radiograph and computer tomography. Unlike 2D ultrasound that captures a planar image, 3D ultrasound technology acquires a 3D volume of information that enables multiple planes of view by manipulating the image without movement of the ultrasound probe. Observation of the brachial plexus in cross-section demonstrated distinct linear hyperechoic tissue structures (loose connective tissue) that initially inhibited the flow of the local anesthesia. After completion of the injection, we were able to visualize the influence of arterial pulsation on the spread of the local anesthesia. Possible advantages of this novel technology over current 2D methods are wider image volume and the capability to manipulate the planes of the image without moving the probe.

Involvement of pterygoid venous plexus in patulous eustachian tube symptoms.

PubMed

Oshima, Takeshi; Ogura, Masaki; Kikuchi, Toshiaki; Hori, Yoko; Mugikura, Shunji; Higano, Shuichi; Takahashi, Shoki; Kawase, Tetsuaki; Kobayashi, Toshimitsu

2007-07-01

The pterygoid venous plexus (PVP) is an important factor in the mechanism of eustachian tube (ET) closure under conditions that can cause increased venous pressure in the head, such as during neck compression and postural change from the sitting/standing to the recumbent position. The symptoms of patulous ET are usually improved by neck compression or postural change (from sitting/standing to recumbent position). Venous congestion around the ET and/or gravitational change may be involved in the changing degree of symptoms, but its mechanism is not understood. This study investigated whether the PVP is involved. The dimensions of soft tissues surrounding ET were measured on magnetic resonance images before and after neck compression. The lateral pterygoid muscle became enlarged after neck compression. Simultaneously, the volume of venous plexus observed between the medial pterygoid muscle and tensor veli palatini muscle was increased. Such enlargement was probably due to blood pooling in the PVP, resulting in protrusion of the ET anterior wall to the luminal side, and decreased ET patency.

Rapid, automated mosaicking of the human corneal subbasal nerve plexus.

PubMed

Vaishnav, Yash J; Rucker, Stuart A; Saharia, Keshav; McNamara, Nancy A

2017-11-27

Corneal confocal microscopy (CCM) is an in vivo technique used to study corneal nerve morphology. The largest proportion of nerves innervating the cornea lie within the subbasal nerve plexus, where their morphology is altered by refractive surgery, diabetes and dry eye. The main limitations to clinical use of CCM as a diagnostic tool are the small field of view of CCM images and the lengthy time needed to quantify nerves in collected images. Here, we present a novel, rapid, fully automated technique to mosaic individual CCM images into wide-field maps of corneal nerves. We implemented an OpenCV image stitcher that accounts for corneal deformation and uses feature detection to stitch CCM images into a montage. The method takes 3-5 min to process and stitch 40-100 frames on an Amazon EC2 Micro instance. The speed, automation and ease of use conferred by this technique is the first step toward point of care evaluation of wide-field subbasal plexus (SBP) maps in a clinical setting.

High-resolution nerve ultrasound and magnetic resonance neurography as complementary neuroimaging tools for chronic inflammatory demyelinating polyneuropathy

PubMed Central

Pitarokoili, Kalliopi; Kronlage, Moritz; Bäumer, Philip; Schwarz, Daniel; Gold, Ralf; Bendszus, Martin; Yoon, Min-Suk

2018-01-01

Background: We present a clinical, electrophysiological, sonographical and magnetic resonance neurography (MRN) study examining the complementary role of two neuroimaging methods of the peripheral nervous system for patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Furthermore, we explore the significance of cross-sectional area (CSA) increase through correlations with MRN markers of nerve integrity. Methods: A total of 108 nerve segments on the median, ulnar, radial, tibial and fibular nerve, as well as the lumbar and cervical plexus of 18 CIDP patients were examined with high-resonance nerve ultrasound (HRUS) and MRN additionally to the nerve conduction studies. Results: We observed a fair degree of correlation of the CSA values for all nerves/nerve segments between the two methods, with a low random error in Bland–Altman analysis (bias = HRUS-CSA − MRN-CSA, −0.61 to −3.26 mm). CSA in HRUS correlated with the nerve T2-weighted (nT2) signal increase as well as with diffusion tensor imaging parameters such as fractional anisotropy, a marker of microstructural integrity. HRUS-CSA of the interscalene brachial plexus correlated significantly with the MRN-CSA and nT2 signal of the L5 and S1 roots of the lumbar plexus. Conclusions: HRUS allows for reliable CSA imaging of all peripheral nerves and the cervical plexus, and CSA correlates with markers of nerve integrity. Imaging of proximal segments as well as the estimation of nerve integrity require MRN as a complementary method. PMID:29552093

Timing of rehabilitation in children with obstetric upper trunk brachial plexus palsy.

PubMed

Yilmaz, Volkan; Umay, Ebru; Tezel, Nihal; Gundogdu, Ibrahim

2018-06-01

The initiation timing of rehabilitation in children with obstetric brachial plexus palsy is controversial. The aim of the present study is to evaluate the effectiveness of rehabilitation timing to the functional outcomes of patients with obstetric upper trunk brachial plexus palsy. Twenty-nine patients, who did not previously received any rehabilitation programme but attended our outpatient clinic, were included for the study. The electrophysiological findings, obstetric characteristics, and demographic features of the patients were recorded. The range of motion (ROM) of shoulders, elbows, and wrists and the strength of the muscles associated with these joints were evaluated. Modified Mallet Scale (MMS) was used for functional evaluation. A 4-week rehabilitation programme was performed twice at 2-month intervals. Patients were divided into three groups according to their ages as follows: 1-3 years old (group 1), 3-5 years old (group 2), and 5-7 years old (group 3). The ROMs, muscle strengths, and MMS scores of the patients were all evaluated. Two out of 29 patients were female (6.9%) and 27 were male (93.1%). All 29 patients had right upper extremity palsy (100%). The MMS scores, ROMs, and muscle strength of the upper extremities had improved in all the groups following the standardized rehabilitation programme. A rehabilitation programme is the best choice of treatment before surgical procedures in patients with mild to moderate obstetric upper trunk brachial plexus palsy regardless of age and the initiation time.

Reconstructive operations for the upper limb after brachial plexus palsy.

PubMed

Rühmann, Oliver; Schmolke, Stephan; Bohnsack, Michael; Carls, Jörg; Flamme, Christian; Wirth, Carl Joachim

2004-07-01

Limited function due to paralysis following brachial plexus lesions can be improved by secondary operations of the bony and soft tissue. Between April 1994 and December 2000, 109 patients suffering from arm-plexus lesions underwent a total of 144 reconstructive operations guided by our concept of integrated therapy. The average age at the time of surgery was 32 years (range: 15-59). The following operations were performed: shoulder arthrodesis (23), trapezius transfer (74), rotation osteotomy of humerus (9), triceps to biceps transposition (9), transposition of forearm flexors or extensors (8), latissimus transfer (7), pectoralis transfer (1), teres major transfer (1), transposition of flexor carpi ulnaris to the tendons of extensor digitorum (10), and wrist arthrodesis (2). Prospectively, in all patients, the grade of muscle power of the affected upper extremity was evaluated prior to surgery. The follow-up period for all 144 operations was, on average, 22 months (range: 6-74). By means of operative measures, almost all patients obtained an improvement of shoulder function (100%) and stability (>90%), elbow flexion (85%), and hand, finger, and thumb (100%). When muscles malfunction after brachial plexus lesions, one should take into account the individual neuromuscular defect, passive joint function, and bony deformities; different procedures such as muscle transpositions, arthrodeses, and corrective osteotomies can then be performed to improve function of the upper extremity. Each form of operative treatment presents patients with certain benefits and all are integrated into a total treatment plan for the affected extremity.

Local infiltration analgesia versus continuous interscalene brachial plexus block for shoulder replacement pain: a randomized clinical trial.

PubMed

Bjørnholdt, Karen T; Jensen, Jan M; Bendtsen, Thomas F; Søballe, Kjeld; Nikolajsen, Lone

2015-12-01

Shoulder replacement involves significant post-operative pain, which is often managed by continuous interscalene brachial plexus block. Catheter displacement and complications limit the beneficial effect of the block. Local infiltration analgesia (LIA) has provided good results in knee replacement. We aimed to assess the effectiveness of LIA for pain after shoulder replacement. Patients scheduled for primary shoulder replacement under general anaesthesia were randomized to receive either local infiltration analgesia (LIA) (150 ml ropivacaine 0.2 % with epinephrine intra-operatively) or interscalene brachial plexus catheter (ISC) (ropivacaine 0.75 %, 7 ml bolus followed by 48-h 5 ml/h infusion). The primary outcome was opioid consumption during the first 24 post-operative hours. Secondary outcomes were pain ratings, supplementary analgesics, and side effects for 3 days, and complications until 3 months after surgery. Data were analysed for 61 patients (LIA 30, ISC 31). Twenty-four-hour opioid consumption was higher in the LIA group compared with the ISC group: median (IQR) 95 mg (70-150 mg) versus 40 mg (8-76 mg) (P = 0.0001). No significant difference in opioid consumption was found between groups during the following 3 days. The LIA group had higher pain scores at 0, 2, 4, and 8 h. Two patients in the ISC group had long-lasting complications. The LIA technique cannot be recommended for shoulder replacement unless substantially modified. Occurrence of inadequate analgesia and complications following interscalene brachial plexus block prompt further studies into pain management after shoulder replacement.

[Group B streptococcus meningitis and infection surrounding the spinal canal caused by bacterial transmission from rectal ulcer via Batson's plexus].

PubMed

Tsutsumi, Ryosuke; Saito, Masaaki; Yoshizawa, Toshihiro

2011-07-01

A 62-year-old man was admitted to our hospital because of fever and disturbed consciousness. He suffered from persistent constipation due to diabetic autonomic neuropathy. On admission, neck stiffness and weakness of the lower extremities were observed. Cerebrospinal fluid (CSF) pleocytosis and decreased CSF glucose concentration showed the presence of meningitis. Bacterial culture of CSF was negative. One week after admission, he suddenly suffered from massive bleeding from the rectum, where a hemorrhagic ulcer caused by severe persistent constipation was observed. Contrast-enhanced CT scans and gadolinium-enhanced MR scans demonstrated a lumbar spinal epidural abscess, paraspinal muscle abscess, and cervical osteomyelitis. Streptococcus agalactiae, a bacterial species belonging to the group B streptococci, was isolated from pus obtained by needle puncture of the paraspinal muscle abscess. His entire condition was treated successfully with ampicillin and cefotaxime. Group B streptococci normally colonize the mucous membrane of the genital or lower gastrointestinal regions and rarely cause a spinal epidural abscess. However, in this case, the existence of a rectal ulcer probably made it possible for S. agalactiae to cause an infection of the epidural space or paraspinal muscles via the spinal valveless venous system named Batson's plexus communicating with the sacral, pelvic, and prostatic venous plexus. Our case indicated the importance of Batson's plexus in group B streptococcus infections surrounding the spinal canal and the necessity to explore for intrapelvic lesions including a rectal ulcer.

Demystifying MR Neurography of the Lumbosacral Plexus: From Protocols to Pathologies

PubMed Central

Muniz Neto, Francisco J.; Kihara Filho, Eduardo N.; Miranda, Frederico C.; Rosemberg, Laercio A.; Santos, Durval C. B.

2018-01-01

Magnetic resonance neurography is a high-resolution imaging technique that allows evaluating different neurological pathologies in correlation to clinical and the electrophysiological data. The aim of this article is to present a review on the anatomy of the lumbosacral plexus nerves, along with imaging protocols, interpretation pitfalls, and most common pathologies that should be recognized by the radiologist: traumatic, iatrogenic, entrapment, tumoral, infectious, and inflammatory conditions. An extensive series of clinical and imaging cases is presented to illustrate key-points throughout the article. PMID:29662907

Upper Extremity Regional Anesthesia

PubMed Central

Neal, Joseph M.; Gerancher, J.C.; Hebl, James R.; Ilfeld, Brian M.; McCartney, Colin J.L.; Franco, Carlo D.; Hogan, Quinn H.

2009-01-01

Brachial plexus blockade is the cornerstone of the peripheral nerve regional anesthesia practice of most anesthesiologists. As part of the American Society of Regional Anesthesia and Pain Medicine’s commitment to providing intensive evidence-based education related to regional anesthesia and analgesia, this article is a complete update of our 2002 comprehensive review of upper extremity anesthesia. The text of the review focuses on (1) pertinent anatomy, (2) approaches to the brachial plexus and techniques that optimize block quality, (4) local anesthetic and adjuvant pharmacology, (5) complications, (6) perioperative issues, and (6) challenges for future research. PMID:19282714

Management of Shoulder Problems Following Obstetric Brachial Plexus Injury

PubMed Central

Nixon, Matthew; Trail, Ian

2013-01-01

Obstetric brachial plexus injuries are common, with an incidence of 0.42 per 1000 live births in the UK, and with 25% of patients being left with permanent disability without intervention. The shoulder is the most commonly affected joint and, as a result of the subsequent imbalance of musculature, the abnormal deforming forces cause dysplasia of the glenohumeral joint. In the growing child, this presents with changing pattern of pathology, which requires a multidisciplinary approach and a broad range of treatment modalities to optimize function. PMID:27582903

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system.

PubMed

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-09-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. © 2013 Anatomical Society.

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system

PubMed Central

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-01-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. PMID:23834399

Regional variation in contribution of myenteric and intramuscular interstitial cells of Cajal to generation of slow waves in mouse gastric antrum

PubMed Central

Hirst, G D S; Beckett, E A H; Sanders, K M; Ward, S M

2002-01-01

When intracellular recordings were made from the antral region of murine stomach, cells with three different patterns of electrical activity were detected. One group of cells generated follower potentials, the second group generated pacemaker potentials and the third group generated slow waves that consisted of primary and secondary components. Slow waves recorded in different regions of the gastric antrum had similar amplitudes but different characteristic shapes. At the greater curvature, slow waves had large initial components. Midway between the greater and lesser curvature, the amplitude of the initial component was reduced and at the lesser curvature an initial component was difficult to detect. When the distributions of myenteric (ICC-MY) and intramuscular interstitial cells of Cajal (ICC-IM) were determined, using an antibody to Kit, ICC-MY were found to be present at the greater curvature but were greatly reduced in density at the lesser curvature. In contrast, ICC-IM were found in the circular layer of each region. When recordings were made from the antrum of W/WV mice, which lack ICC-IM, incomplete slow waves were detected and their amplitudes fell from the greater to the lesser curvature. Again, a corresponding fall in the density of ICC-MY was detected. The observations indicate that the contribution of ICC-MY and ICC-IM to the generation of slow waves varies in different regions of the mouse gastric antrum. PMID:11986385

Measurements of the contact force from myenteric contractions on a solid bolus.

PubMed

Terry, Benjamin S; Schoen, Jonathan A; Rentschler, Mark E

2013-03-01

The development of robotic capsule endoscopes (RCEs) is one avenue presently investigated by multiple research groups to minimize invasiveness and enhance outcomes of enteroscopic procedures. Understanding the biomechanical response of the small bowel to RCEs is needed for design optimization of these devices. In previous work, the authors developed, characterized, and tested the migrating motor complex force sensor (MFS), a novel sensor for quantifying the contact forces per unit of axial length exerted by the myenteron on a solid bolus. This work is a continuation, in which the MFS is used to quantify the contractile strength in the small intestine proximal, middle, and distal regions of five live porcine models. The MFSs are surgically implanted in a generally anesthetized animal, and force data from 5 min of dwell time are analyzed. The mean myenteric contact force from all porcine models and locations within the bowel is 1.9 ± 1.0 N cm(-1). Examining the results based on the small bowel region shows a statistically significant strengthening trend in the contractile force from proximal to middle to distal with mean forces of 1.2 ± 0.5, 1.9 ± 0.9, and 2.3 ± 1.0 N cm(-1), respectively (mean ± one standard deviation). Quantification of the contact force against a solid bolus provides developers of RCEs with a valuable, experimentally derived parameter of the intraluminal environment.

Topographical and functional anatomy of trapezius muscle innervation by spinal accessory nerve and C2 to C4 nerves of cervical plexus.

PubMed

Gavid, M; Mayaud, A; Timochenko, A; Asanau, A; Prades, J M

2016-10-01

The aim of this study was to determine the existence and the frequency of communicating branches between the spinal accessory nerve (SAN) and the C2, C3 and C4 roots of the cervical plexus. The present study also aimed to elucidate whether these branches contain motor fibers or not. Dissection of the cervical region was performed on twelve adult cadavers. A powered operating microscope was necessary to dissect the SAN and its branches and also to dissect C2, C3 and C4 nerve branches. In a second step, data from 13 patients who underwent 25 modified neck dissections under trapezius muscle's monitoring were collected. At the end of surgery, intraoperative stimulation on the SAN, C2, C3 and C4 nerve branches was performed. Registered potentials in the three parts of the trapezius muscle, using the NIM Medtronic system, were analyzed. During cadaver dissection, 18 (78 %) communicating branches were identified between the SAN and C2, 11 (48 %) between the SAN and C3, 12 (52 %) between the SAN and C4. Intraoperative stimulation of the SAN and its branch for the trapezius muscle provided a significant electroneurographic response in the three parts of the trapezius muscle in all subjects. Intraoperative stimulation of C3 led to recordable contractions of the trapezius muscle in 5 (20 %) modified neck surgeries, stimulation of C4 led to recordable contractions during 5 (20 %) modified neck dissections. One case of contraction was recorded after intraoperative stimulation of C2 (7 %). Although we were able to identify at least one communicating branch between the SAN and the roots of the cervical plexus in each cadaver dissection, the cervical plexus is not always involved in trapezius motor innervation. Intraoperative electroneurography demonstrated that a motor input from the cervical plexus to the trapezius muscle was provided in only 32 % of cases. Therefore, SAN trunk and C3-C4 roots should be carefully preserved during modified neck dissection to protect trapezius and shoulder functions.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT AT 2-MONTH INTERVALS REDUCES FOVEAL AVASCULAR ZONE ENLARGEMENT AND VISION LOSS IN RADIATION MACULOPATHY: A Pilot Study.

PubMed

Daruich, Alejandra; Matet, Alexandre; Schalenbourg, Ann; Zografos, Leonidas

2018-05-03

To evaluate, in eyes with radiation maculopathy, the effect of 2-month-interval anti-vascular endothelial growth factor therapy on best-corrected visual acuity and foveal avascular zone (FAZ) enlargement using optical coherence tomography angiography. Consecutive treatment-naive patients with radiation maculopathy after proton beam irradiation for choroidal melanoma were retrospectively included. Clinical and optical coherence tomography angiography data at baseline and the 6-month visit were recorded. Two independent observers measured FAZ area manually on 3 × 3-mm optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus. Patients were encouraged to follow strictly a 2-month-interval intravitreal anti-vascular endothelial growth factor treatment by either bevacizumab or ranibizumab. Findings were analyzed based on the adherence to the treatment scheme. According to the adherence to the bimonthly anti-vascular endothelial growth factor treatment protocol, patients were categorized into 3 groups: treatment protocol (n = 19, strict adherence), variable intervals (n = 11, intervals other than 2 months), and no treatment (n = 11). The estimated radiation dose to the foveola in each group was 49 ± 16, 46 ± 17, and 46 ± 18 cobalt gray equivalent, respectively (P = 0.85). For the entire cohort, best-corrected visual acuity loss (P < 0.02) and FAZ enlargement (P < 0.0001) were observed over 6 months. Best-corrected visual acuity loss was significantly less pronounced in the treatment-protocol group than in the variable-interval and no-treatment groups (P = 0.007 and P = 0.004). The FAZ enlargement was lower in the treatment-protocol group compared with the variable-interval group for both superficial capillary plexus (P = 0.029) and deep capillary plexus (P = 0.03), and to the no-treatment group for the deep capillary plexus only (P = 0.016). Decrease in best-corrected visual acuity and FAZ enlargement on optical coherence tomography angiography occurred over 6 months in eyes with radiation maculopathy and were significantly reduced under 2-month-interval anti-vascular endothelial growth factor therapy.

Optical Coherence Tomography Angiography of Retinal Microvascular Changes Overlying Choroidal Nodules in Neurofibromatosis Type 1

PubMed Central

Cassiman, Catherine; Casteels, Ingele; Stalmans, Peter; Legius, Eric; Jacob, Julie

2017-01-01

Purpose To report 3 cases of neurofibromatosis type 1 (NF1) with choroidal nodules associated with retinal microvascular changes imaged with optical coherence tomography angiography (OCTA). Methods Small case series in 3 NF1 patients. OCTA examinations were performed by a trained examiner (J.J.) after pupillary dilation. A standard scan, centered over the macula measuring 6 × 6 mm and 3 × 3 mm was obtained according to the findings on standard color photography. Additional scans were obtained in the zones with microvascular abnormalities. The segmentation provided by the machine software was used. Results Corkscrew retinal vessels were observed in association with “placoid”-type choroidal nodules as shown by near-infrared reflectance imaging. In all cases, multiple lesions were found. They were second- or third-order tortuous vessels originating from the superior or inferior temporal veins. OCTA demonstrated that the tortuous venules were located in the superficial capillary plexus, and no abnormalities were found in the deep capillary plexus. Discussion Corkscrew retinal vessels are part of a spectrum of retinal microvascular alterations seen in association, sometimes overlying choroidal nodules in patients with NF1 and are visualized in the superficial capillary plexus on OCTA. We demonstrated with OCTA that they are not associated with flow loss or ischemia in the superficial and deep capillary plexus. The link between the underlying nodule remains unclear. Since neovascularization was described in choroidal ganglioneuroma, we hypothesize that corresponding secretory substances from Schwann cells, ganglion cells, or melanocytes in choroidal nodules might alter the retinal vasculature. Conclusion We report on 3 cases of NF1 with choroidal nodules in association with retinal microvascular changes imaged with OCTA. OCTA demonstrated preservation of the blood flow in the deep and superficial capillary plexus of the retina. We hypothesize that angiogenic factors secreted by the underlying choroidal nodules could have an effect on the retinal vasculature. Further immunohistological studies in NF1 patients with choroidal nodules to detect angiogenic factors (such as VEGF) are necessary to confirm this hypothesis. PMID:28512424

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundstedt, Dan, E-mail: dan.lundstedt@gu.se; Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg; Gustafsson, Magnus

Purpose: To identify volume and dose predictors of paresthesia after irradiation of the brachial plexus among women treated for breast cancer. Methods and Materials: The women had breast surgery with axillary dissection, followed by radiation therapy with (n=192) or without irradiation (n=509) of the supraclavicular lymph nodes (SCLNs). The breast area was treated to 50 Gy in 2.0-Gy fractions, and 192 of the women also had 46 to 50 Gy to the SCLNs. We delineated the brachial plexus on 3-dimensional dose-planning computerized tomography. Three to eight years after radiation therapy the women answered a questionnaire. Irradiated volumes and doses were calculated andmore » related to the occurrence of paresthesia in the hand. Results: After treatment with axillary dissection with radiation therapy to the SCLNs 20% of the women reported paresthesia, compared with 13% after axillary dissection without radiation therapy, resulting in a relative risk (RR) of 1.47 (95% confidence interval [CI] 1.02-2.11). Paresthesia was reported by 25% after radiation therapy to the SCLNs with a V{sub 40} {sub Gy} ≥ 13.5 cm{sup 3}, compared with 13% without radiation therapy, RR 1.83 (95% CI 1.13-2.95). Women having a maximum dose to the brachial plexus of ≥55.0 Gy had a 25% occurrence of paresthesia, with RR 1.86 (95% CI 0.68-5.07, not significant). Conclusion: Our results indicate that there is a correlation between larger irradiated volumes of the brachial plexus and an increased risk of reported paresthesia among women treated for breast cancer.« less

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

PubMed Central

Strazielle, Nathalie; Ghersi-Egea, Jean-François

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

PubMed

Taniguchi, Kan; Matsuura, Kimio; Matsuoka, Takanori; Nakatani, Hajime; Nakano, Takumi; Furuya, Yasuo; Sugimoto, Takeki; Kobayashi, Michiya; Araki, Keijiro

2005-06-01

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Diaphragm-Sparing Nerve Blocks for Shoulder Surgery.

PubMed

Tran, De Q H; Elgueta, Maria Francisca; Aliste, Julian; Finlayson, Roderick J

Shoulder surgery can result in significant postoperative pain. Interscalene brachial plexus blocks (ISBs) constitute the current criterion standard for analgesia but may be contraindicated in patients with pulmonary pathology due to the inherent risk of phrenic nerve block and symptomatic hemidiaphragmatic paralysis. Although ultrasound-guided ISB with small volumes (5 mL), dilute local anesthetic (LA) concentrations, and LA injection 4 mm lateral to the brachial plexus have been shown to reduce the risk of phrenic nerve block, no single intervention can decrease its incidence below 20%. Ultrasound-guided supraclavicular blocks with LA injection posterolateral to the brachial plexus may anesthetize the shoulder without incidental diaphragmatic dysfunction, but further confirmatory trials are required. Ultrasound-guided C7 root blocks also seem to offer an attractive, diaphragm-sparing alternative to ISB. However, additional large-scale studies are needed to confirm their efficacy and to quantify the risk of periforaminal vascular breach. Combined axillary-suprascapular nerve blocks may provide adequate postoperative analgesia for minor shoulder surgery but do not compare favorably to ISB for major surgical procedures. One intriguing solution lies in the combined use of infraclavicular brachial plexus blocks and suprascapular nerve blocks. Theoretically, the infraclavicular approach targets the posterior and lateral cords, thus anesthetizing the axillary nerve (which supplies the anterior and posterior shoulder joint), as well as the subscapular and lateral pectoral nerves (both of which supply the anterior shoulder joint), whereas the suprascapular nerve block anesthetizes the posterior shoulder. Future randomized trials are required to validate the efficacy of combined infraclavicular-suprascapular blocks for shoulder surgery.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Quantification of Trapezius Muscle Innervation During Neck Dissections: Cervical Plexus Versus the Spinal Accessory Nerve.

PubMed

Svenberg Lind, Clara; Lundberg, Bertil; Hammarstedt Nordenvall, Lalle; Heiwe, Susanne; Persson, Jonas K E; Hydman, Jonas

2015-11-01

Despite increasing use of selective, nerve-sparing surgical techniques during neck dissections, the reported rate of postoperative paralysis of the trapezius muscle is still high. The aim of the study is to measure and compare motor inflow to the trapezius muscle, in order to better understand the peripheral neuroanatomy. Intraoperative nerve monitoring (electroneurography) in patients undergoing routine neck dissection (n=18). The innervation of the 3 functional parts of the trapezius muscle was mapped and quantified through compound muscle action potentials. In 18/18 (100%) of the patients, the spinal accessory nerve (SAN) innervated all parts of the trapezius muscle. In 7/18 (39%) of the patients, an active motor branch from the cervical plexus was detected, equally distributed to all functional parts of the trapezius muscle, at levels comparable to the SAN. Compared to the SAN, branches from cervical plexus provide a significant amount of neural input to all parts of the trapezius muscle. Intraoperative nerve monitoring can be used in routine neck dissections to detect these branches, which may be important following surgical injury to the SAN. © The Author(s) 2015.

Acute myelopathy selectively involving lumbar anterior horns following intranasal insufflation of ecstasy and heroin

PubMed Central

Riva, Nilo; Riva, Nilo; Morana, Paolo; Cerri, Federica; Gerevini, Simonetta; Amadio, Stefano; Formaglio, Fabio; Comi, Giancarlo; Comola, Mauro; Del Carro, Ubaldo

2009-01-01

We report a patient who developed acute myelopathy after intranasal insufflation of amphetamines and heroin. The functional prognosis was very poor; after 4 months, she remained paraplegic. MRI imaging showed selective T2 hyperintensity and intense enhancement confined to the spinal anterior horns and lumbar nerve roots and plexus. This unique MRI pattern, together with neurophysiological data, suggests that the pathological process at the first primary affected spinal anterior horns (SAH), conditioning motoneuron cell death, and then nerve roots and lumbar plexus as a consequence of wallerian degeneration PMID:21686691

[Microsurgical treatment of brachial plexus injuries].

PubMed

Päzolt, H J

1986-01-01

Injuries of the brachial plexus are found to occur primarily to juvenile patients as a consequence of motorcycle accidents. While it is a severe injury, its prognosis has been substantively improved by the availability of microsurgical treatment, using long nerve transplants. Further improvement of results will be possible by early operation, a desirable objective. 44 patients with brachial palsy received treatment, including surgery in 41 cases. An account is given in this paper of intraoperative findings, surgical techniques, and results from follow-up checks. The need is underlined for long-term intensive after-care for the purpose of occupational reintegration.

[Pulley for strengthening a muscle replacement operation across two joints in brachial plexus lesion: description of the surgical technique].

PubMed

Berger, A; Schaller, E; Becker, M H

1994-01-01

The reconstruction of lost muscle functions in cases of brachial plexus lesion is possible even in those cases where primary nerve reconstruction was not performed or unsuccessful. If there are only few motor nerves available, we prefer free latissimus dorsi transplantation or pedicled latissimus dorsi transposition for replacement of biceps and finger flexors. The combination of elbow flexion and finger flexion becomes possible when the transposed motor is passed around a suitable pulley in the elbow region like the flexor carpi ulnaris or carpi radialis.

The γ-Glutamyl Cycle in the Choroid Plexus: Its Possible Function in Amino Acid Transport

PubMed Central

Tate, Suresh S.; Ross, Leonard L.; Meister, Alton

1973-01-01

Various anatomic regions of rabbit brain have been examined for activities of the enzymes of the γ-glutamyl cycle. While these enzyme activities were widely distributed in the brain, they are present in much higher concentrations in the choroid plexus than in other parts of the brain. The activities observed are of about the same order of magnitude as found in the kidney. These observations and other considerations suggest that the γ-glutamyl cycle may play a significant role in the transport of amino acids between blood and cerebrospinal fluid. PMID:4145786

Clinical aspects of patients with traumatic lesions of the brachial plexus following surgical treatment☆

PubMed Central

de Moraes, Frederico Barra; Kwae, Mário Yoshihide; da Silva, Ricardo Pereira; Porto, Celmo Celeno; Magalhães, Daniel de Paiva; Paulino, Matheus Veloso

2015-01-01

Objective To evaluate sociodemographic and clinical aspects of patients undergoing operations due to traumatic lesions of the brachial plexus. Method This was a retrospective study in which the medical files of a convenience sample of 48 patients operated between 2000 and 2010 were reviewed. The following were evaluated: (1) range of motion (ROM) of the shoulder, elbow and wrist/hand, in degrees; (2) grade of strength of the shoulder, elbow and wrist/hand; (3) sensitivity; and (4) visual analogue scale (VAS) (from 0 to 10). The Student's t, chi-square, Friedman, Wilcoxon and Kruskal–Wallis tests were used (p < 0.05). Results The patients’ mean age was 30.6 years; 60.4% of them had suffered motorcycle accidents and 52.1%, multiple trauma. The mean length of time until surgery was 8.7 months (range: 2–48). Thirty-one patients (64.6%) presented complete rupture of the plexus. The frequent operation was neurosurgery in 39 cases (81.3%). The ROM achieved was ≥30° in 20 patients (41.6%), with a range from 30° to 90° and mean of 73° (p = 0.001). Thirteen (27.1%) already had shoulder strength ≥M3 (p = 0.001). Twenty-seven patients (56.2%) had elbow flexion ≥80°, with a range from 30° to 160° and mean of 80.6° (p < 0.001). Twenty-two had strength ≥M3 (p < 0.001). Twenty-two patients (45.8%) had wrist extension ≥30° starting from flexion of 45°, with a range from 30° to 90° and mean of 70° (p = 0.003). Twenty-seven (56.3%) presented wrist/hand extension strength ≥M3 (p = 0.002). Forty-five (93.8%) had hypoesthesia and three (6.2%) had anesthesia (p = 0.006). The initial VAS was 4.5 (range: 1.0–9.0) and the final VAS was 3.0 (range: 1.0–7.0) (p < 0.001). Conclusion Traumatic lesions of the brachial plexus were more prevalent among young adults (21–40 years), men, people living in urban areas, manual workers and motorcycle accidents, with multiple trauma and total rupture of the plexus. Neurosurgery, with a second procedure consisting of muscle-tendon transfer, was the commonest operation. Surgery for traumatic lesions of the brachial plexus resulted in significant improvement in the ROM and strength of the shoulder, elbow and wrist/hand, improvement of the sensitivity of the limb affected and reduction of the final pain. PMID:26535203

A comparative study of nerve stimulator versus ultrasound-guided supraclavicular brachial plexus block.

PubMed

Duncan, Mithun; Shetti, Akshaya N; Tripathy, Debendra Kumar; Roshansingh, D; Krishnaveni, N

2013-01-01

With the advent of ultrasound (US) guidance, this technique saw resurgence in the late 1990s. As US guidance provides real-time view of the block needle, the brachial plexus, and its spatial relationship to the surrounding vital structures; it not only increased the success rates, but also brought down the complication rates. Most of the studies show use of US guidance for performing brachial plexus block, results in near 100% success with or without complications. This study has been designed to examine the technique and usefulness of state-of-the-art US technology-guided supraclavicular brachial plexus block and compare it with routine nerve stimulator (NS)-guided technique. To note block execution time, time of onset of sensory and motor block, quality of block and success rates. Randomized controlled trial. A total of 60 patients were enrolled in this prospective randomized study and were randomly divided into two groups: US (Group US) and NS (Group NS). Both groups received 1:1 mixture of 0.5% bupivacaine and 2% lignocaine with 1:200000 adrenaline. The amount of local anaesthetic injected calculated according to the body weight and not crossing the toxic dosage (Inj. bupivacaine 2 mg/kg, Inj. lignocaine with adrenaline 7 mg/kg). The parameters compared between the two groups are block execution time, time of onset of sensory and motor block, quality of sensory and motor block, success rates are noted. The failed blocks are supplemented with general anesthesia. The data were analyzed using the SPSS (version 19) software. The parametric data were analyzed with student "t" test and the nonparametric data were analyzed with Chi-square test A P < 0.05 was considered significant. There was no significant difference between patient groups with regard to demographic data, the time of onset of sensory and motor block. Comparing the two groups, we found that the difference in the block execution time and success rates is not statistically significant. A failure rate of 10% in US and 20% in NS group observed and is statistically insignificant (P = 0.278). No complication observed in either group. US and NS group guidance for performing supraclavicular brachial plexus blocks ensures a high success rate and a decreased incidence of complications that are associated with the blind technique. However, our study did not prove the superiority of one technique over the other. The US-guided technique seemed to have an edge over the NS-guided technique. A larger study may be required to analyze the advantages of using US in performing supraclavicular brachial plexus blocks, which could help justify the cost of purchase of the US machine.

Evaluation of nerve transfer options for treating total brachial plexus avulsion injury: a retrospective study of 73 participants

PubMed Central

Gao, Kai-ming; Hu, Jing-jing; Lao, Jie; Zhao, Xin

2018-01-01

Despite recent great progress in diagnosis and microsurgical repair, the prognosis in total brachial plexus-avulsion injury remains unfavorable. Insufficient number of donors and unreasonable use of donor nerves might be key factors. To identify an optimal treatment strategy for this condition, we conducted a retrospective review. Seventy-three patients with total brachial plexus avulsion injury were followed up for an average of 7.3 years. Our analysis demonstrated no significant difference in elbow-flexion recovery between phrenic nerve-transfer (25 cases), phrenic nerve-graft (19 cases), intercostal nerve (17 cases), or contralateral C7-transfer (12 cases) groups. Restoration of shoulder function was attempted through anterior accessory nerve (27 cases), posterior accessory nerve (10 cases), intercostal nerve (5 cases), or accessory + intercostal nerve transfer (31 cases). Accessory nerve + intercostal nerve transfer was the most effective method. A significantly greater amount of elbow extension was observed in patients with intercostal nerve transfer (25 cases) than in those with contralateral C7 transfer (10 cases). Recovery of median nerve function was noticeably better for those who received entire contralateral C7 transfer (33 cases) than for those who received partial contralateral C7 transfer (40 cases). Wrist and finger extension were reconstructed by intercostal nerve transfer (31 cases). Overall, the recommended surgical treatment for total brachial plexus-avulsion injury is phrenic nerve transfer for elbow flexion, accessory nerve + intercostal nerve transfer for shoulder function, intercostal nerves transfer for elbow extension, entire contralateral C7 transfer for median nerve function, and intercostal nerve transfer for finger extension. The trial was registered at ClinicalTrials.gov (identifier: NCT03166033). PMID:29623932

Finger movement at birth in brachial plexus birth palsy

PubMed Central

Nath, Rahul K; Benyahia, Mohamed; Somasundaram, Chandra

2013-01-01

AIM: To investigate whether the finger movement at birth is a better predictor of the brachial plexus birth injury. METHODS: We conducted a retrospective study reviewing pre-surgical records of 87 patients with residual obstetric brachial plexus palsy in study 1. Posterior subluxation of the humeral head (PHHA), and glenoid retroversion were measured from computed tomography or Magnetic resonance imaging, and correlated with the finger movement at birth. The study 2 consisted of 141 obstetric brachial plexus injury patients, who underwent primary surgeries and/or secondary surgery at the Texas Nerve and Paralysis Institute. Information regarding finger movement was obtained from the patient’s parent or guardian during the initial evaluation. RESULTS: Among 87 patients, 9 (10.3%) patients who lacked finger movement at birth had a PHHA > 40%, and glenoid retroversion < -12°, whereas only 1 patient (1.1%) with finger movement had a PHHA > 40%, and retroversion < -8° in study 1. The improvement in glenohumeral deformity (PHHA, 31.8% ± 14.3%; and glenoid retroversion 22.0° ± 15.0°) was significantly higher in patients, who have not had any primary surgeries and had finger movement at birth (group 1), when compared to those patients, who had primary surgeries (nerve and muscle surgeries), and lacked finger movement at birth (group 2), (PHHA 10.7% ± 15.8%; Version -8.0° ± 8.4°, P = 0.005 and P = 0.030, respectively) in study 2. No finger movement at birth was observed in 55% of the patients in this study group. CONCLUSION: Posterior subluxation and glenoid retroversion measurements indicated significantly severe shoulder deformities in children with finger movement at birth, in comparison with those lacked finger movement. However, the improvement after triangle tilt surgery was higher in patients who had finger movement at birth. PMID:23362472

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

PubMed

Hogendoorn, S; Duijnisveld, B J; van Duinen, S G; Stoel, B C; van Dijk, J G; Fibbe, W E; Nelissen, R G H H

2014-01-01

Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps. Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy. No adverse effects in vital signs, bone marrow aspiration sites, injection sites, or surgical wound were seen. After cell therapy there was a 52% decrease in muscle fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50% increase in satellite cells (p = 0.045) and an 83% increase in capillary-to-myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of 36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and 29% increase in number of phases (p = 0.002). Mononuclear cell injection in partly denervated muscle of brachial plexus patients is safe. The results suggest enhanced muscle reinnervation and regeneration. Cite this article: Bone Joint Res 2014;3:38-47.

Restoration of Elbow Flexion in Patients With Complete Traumatic and Obstetric Brachial Plexus Injury After Functional Free Gracilis Muscle Transfer: Our Experience and Management.

PubMed

Nath, Rahul K; Boutros, Sean G; Somasundaram, Chandra

2017-01-01

Background: Functional free gracilis muscle transfer is an operative procedure for elbow reconstruction in patients with complete brachial plexus nerve and avulsion injuries and in delayed or prolonged nerve denervation, as well as in patients with inadequate upper extremity function after primary nerve reconstruction. Methods: We retrospectively reviewed our patient records and identified 24 patients with complete brachial plexus nerve injury (13 obstetric, 11 males and 2 females; 11 traumatic, 9 males and 2 females) whose affected arm and shoulder were totally paralyzed and their voluntary elbow flexion or the biceps function was poor preoperatively (mean M0-1/5 in MRC grade). These patients had undergone the functional free gracilis muscle transfer procedure at our clinic since 2005. Results: Ninety-two percent of all patients showed recovery and improvement. Successful free gracilis muscle transfer is defined as antigravity biceps muscle strength of M3-4/5 and higher, which was observed in 16 (8 obstetric and 8 traumatic) of our 24 patients (67%) in this study at least 1 year after functional free gracilis muscle transfer. This is statistically significant ( P < .000001) in comparison with their mean preoperative score (M0-1/5). There was no improvement in motor level of the biceps muscle (M0/5) in 2 patients (1 from each group). The donor site of these 24 patients showed no deficit in motor and sensory functions. Conclusions: Taken together, a significant number (92%) of patients in both obstetric and traumatic brachial plexus injury groups had recovery and improvement and most of these patients (64%) achieved antigravity and elbow flexion at least 1 year after free gracilis muscle transfer at our clinic.

Restoration of Elbow Flexion in Patients With Complete Traumatic and Obstetric Brachial Plexus Injury After Functional Free Gracilis Muscle Transfer: Our Experience and Management

PubMed Central

Boutros, Sean G.; Somasundaram, Chandra

2017-01-01

Background: Functional free gracilis muscle transfer is an operative procedure for elbow reconstruction in patients with complete brachial plexus nerve and avulsion injuries and in delayed or prolonged nerve denervation, as well as in patients with inadequate upper extremity function after primary nerve reconstruction. Methods: We retrospectively reviewed our patient records and identified 24 patients with complete brachial plexus nerve injury (13 obstetric, 11 males and 2 females; 11 traumatic, 9 males and 2 females) whose affected arm and shoulder were totally paralyzed and their voluntary elbow flexion or the biceps function was poor preoperatively (mean M0-1/5 in MRC grade). These patients had undergone the functional free gracilis muscle transfer procedure at our clinic since 2005. Results: Ninety-two percent of all patients showed recovery and improvement. Successful free gracilis muscle transfer is defined as antigravity biceps muscle strength of M3-4/5 and higher, which was observed in 16 (8 obstetric and 8 traumatic) of our 24 patients (67%) in this study at least 1 year after functional free gracilis muscle transfer. This is statistically significant (P < .000001) in comparison with their mean preoperative score (M0-1/5). There was no improvement in motor level of the biceps muscle (M0/5) in 2 patients (1 from each group). The donor site of these 24 patients showed no deficit in motor and sensory functions. Conclusions: Taken together, a significant number (92%) of patients in both obstetric and traumatic brachial plexus injury groups had recovery and improvement and most of these patients (64%) achieved antigravity and elbow flexion at least 1 year after free gracilis muscle transfer at our clinic. PMID:29213347