Pathophysiology of aganglionic colon and anorectum: An experimental study on aganglionosis produced by a new method in the rat

Sato, Akio; Yamamoto, Masashi; Imamura, K; Kashiki, Yoshitomo; Kunieda, T; Sakata, Kazuki

doi:10.1016/s0022-3468(78)80464-3

Cited by 99 publications

(75 citation statements)

References 12 publications

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“…BAK induces neurotoxicity directly due to its detergent action and indirectly due to infiltrating inflammatory cells. Sato et al 34 postulated that the neuronal damage of BAK was due to its positive charge. In contrast, Fox et al 35 found that neurotoxicity can be attributed to the generalized property of cationic surfactants rather than to charge specificity.…”

Section: Discussionmentioning

confidence: 99%

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Sarkar¹,

Chaudhary²,

Namavari³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

120

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PURPOSE. The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro.METHODS. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Widefield stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth.RESULTS. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P < 0.05). These changes were most significant after 0.1% BAK treatment. The extent of inflammatory cell infiltration in the cornea showed a significant negative correlation with NFD. Sequential in vivo imaging of corneas showed two forms of BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy and recovery, and irreversible neurotoxicity characterized by nerve degeneration and regeneration. Increased abundance of beta III tubulin in corneal lysates confirmed regeneration. A dose-related significant reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001).CONCLUSION. Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Sarkar¹,

Chaudhary²,

Namavari³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

120

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“…S6A). Previous studies described animal models of aganglionosis that can be obtained by treating the GI tract in vivo with benzalkonium chloride (BC), a surfactant that selectively removes enteric nerve plexuses (Sato et al, 1978;Sakata et al, 1979;Fox and Bass, 1984;Yoneda et al, 2002;Liu et al, 2013a;Shu et al, 2013) without harming smooth muscle tissues (Sato et al, 1978). We then placed GI tracts in 0.04% BC-containing solution for 10 min, washed several times and cultured them in BC-free solution for 36 h before analyses (Fig.…”

Section: Inhibition Of Notch Signaling Is Required For Stomach Pattermentioning

confidence: 99%

Enteric neural crest cells regulate vertebrate stomach patterning and differentiation

et al. 2015

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In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development.

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“…A common useful instrument to study functional aspects of the nervous system and visceral innervation is to verify the effects of removing parts of the nervous system. The development of a new ablation model of the ICNS using benzalkonium chloride (BC) has been investigated over some time [7]. The destruction of intrinsic myoenteric neurons caused by the topical administration of BC on the digestive tract serosa in rats and the fact that this procedure causes great alterations in the physiology and morphology of the organ have already been confirmed.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, there are no descriptions in the literature of a specific experimental model of denervation of the CINS, which preserves the extrinsic system. Benzalkonium chlorate (BC) is a cationic surfactant that, when applied topically to the digestive tract, causes denervation of intrinsic neurons, causing significant alterations to the physiology and morphology of this organ [7,8]. As the cardiac neurons are located in the epicardium [9], by analogy, the intra-pericardial administration of BC should destroy them, producing an experimental model of denervation.…”

Section: Introductionmentioning

confidence: 99%

Um modelo experimental de ablação do Sistema Nervoso Intrínseco Cardíaco reduz a contratilidade do coração de ratos

Filho¹,

Nakamura²,

Faria³

et al. 2004

Rev Bras Cir Cardiovasc

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Introduction: The function of the Intrinsic Cardiac Nervous System is largely unknown, as is its role in heart disease. In the digestive system, a topic application of Benzalkonium chloride leads to intrinsic denervation of the viscera. Thus, our aim was to obtain an experimental model of cardiac intrinsic denervation by the application of Benzalkonium chloride on the heart. Method: Thirty male Wistar rats received intrapericardial injections of 0.3% Benzalkonium chloride (BC animals) and thirty similar animals received saline (C animals). After 15 days the animals were divided in three groups, with 10 CBtreated and 10 saline-treated animals in each. Group I was submitted to radiological and morphologic studies. The cardiac shadow area (CSA) and cardiothoracic index were calculated in roentgenograms with a semi-automatic image analysis system (MINI-MOP). The day after the animals were weighed and sacrificed with heart, liver and lung collected for histopathologic analysis. The animals of Group II were submitted to a hemodynamic study. Measurements of blood pressure, heart rate and cardiac output were performed using the Cardiomax II thermodilution system and a Thermistor sensor. With the animals of the Group III, the integrity of the extrinsic parasympathetic cardiac innervation was examined by measuring heart rate response to electrical stimulation of the right vagus. Electrical activity was assessed by ECG.Results: CB animals presented increases in cardiothoracic index, CSA, body and liver weight. In these animals the histopathologic analysis showed passive chronic congestion and reduction of the number of atrial neurons. In the hemodynamic study, total peripheral resistance and heart rate were similar in both groups, but blood pressure and cardiac index were reduced in the CB group. The vagal stimulation and ECG were similar in both groups.Conclusion: Intrinsic Cardiac Nervous System denervation caused dilated cardiopathy in rats with left and right heart failure. The etiology of some dilated cardiopathies in human is largely unknown. This unpublished experimental model should provide future studies with the objective of elucidating the relationship between neuronal injures and heart disease.

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Pathophysiology of aganglionic colon and anorectum: An experimental study on aganglionosis produced by a new method in the rat

Cited by 99 publications

References 12 publications

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

Enteric neural crest cells regulate vertebrate stomach patterning and differentiation

Um modelo experimental de ablação do Sistema Nervoso Intrínseco Cardíaco reduz a contratilidade do coração de ratos

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