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Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

ABSTRACT: Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles.

SUBMITTER: Moshkin MP

PROVIDER: S-EPMC4150316 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

Moshkin M P MP Petrovski D V DV Akulov A E AE Romashchenko A V AV Gerlinskaya L A LA Ganimedov V L VL Muchnaya M I MI Sadovsky A S AS Koptyug I V IV Savelov A A AA Troitsky S Yu SY Moshkn Y M YM Bukhtiyarov V I VI Kolchanov N A NA Sagdeev R Z RZ Fomin V M VM

Proceedings. Biological sciences 20141001 1792

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the o ...[more]

PMID: 25143031

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Project description:IntroductionActivated Protein C (APC), an endogenous anticoagulant, improves tissue microperfusion and endothelial cell survival in systemic inflammatory states such as sepsis, but intravenous administration may cause severe bleeding. We have thus addressed the role of APC delivered locally by inhalation in preventing acute lung injury from alveolar overdistention and the subsequent ventilator-induced lung injury (VILI). We also assessed the effects of APC on the activation status of Extracellular- Regulated Kinase 1/2 (ERK) pathway, which has been shown to be involved in regulating pulmonary responses to mechanical stretch.MethodsInhaled APC (12.5 microg drotrecogin-alpha x 4 doses) or saline was given to tracheotomized C57/Bl6 mice starting 20 min prior to initiation of injurious mechanical ventilation with tidal volume 25 mL/Kg for 4 hours and then hourly thereafter; control groups receiving inhaled saline were ventilated with 8 mL/Kg for 30 min or 4 hr. We measured lung function (respiratory system elastance H), arterial blood gases, surrogates of vascular leak (broncho-alveolar lavage (BAL) total protein and angiotensin-converting enzyme (ACE)-activity), and parameters of inflammation (BAL neutrophils and lung tissue myeloperoxidase (MPO) activity). Morphological alterations induced by mechanical ventilation were examined in hematoxylin-eosin lung tissue sections. The activation status of ERK was probed in lung tissue homogenates by immunoblotting and in paraffin sections by immunohistochemistry. The effect of APC on ERK signaling downstream of the thrombin receptor was tested on A549 human lung epithelial cells by immunoblotting. Statistical analyses were performed using ANOVA with appropriate post-hoc testing.ResultsIn mice subjected to VILI without APC, we observed hypoxemia, increased respiratory system elastance and inflammation, assessed by BAL neutrophil counts and tissue MPO activity. BAL total protein levels and ACE activity were also elevated by VILI, indicating compromise of the alveolo-capillary barrier. In addition to preserving lung function, inhaled APC prevented endothelial barrier disruption and attenuated hypoxemia and the inflammatory response. Mechanistically, we found a strong activation of ERK in lung tissues by VILI, which was prevented by APC, suggestive of pathogenetic involvement of the Mitogen-Activated Kinase pathway. In cultured human lung epithelial cells challenged by thrombin, APC abrogated the activation of ERK and its downstream effector, cytosolic Phospholipase A2.ConclusionsTopical application of APC by inhalation may effectively reduce lung injury induced by mechanical ventilation in mice.

Project description:BackgroundAbnormal nasal aerodynamics or trigeminal functions have been frequently implicated in the symptomology of empty nose syndrome (ENS), yet with limited evidence.MethodsIndividual computed tomography (CT)-based computational fluid dynamics (CFD) was applied to 27 ENS patients to simulate their nasal aerodynamics and compared with 42 healthy controls. Patients' symptoms were confirmed with Empty Nose Syndrome 6-item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), and Nasal Obstruction Symptom Evaluation (NOSE) scores. Nasal trigeminal sensitivity was measured with menthol lateralization detection thresholds (LDTs).ResultsENS patients had significantly lower (∼25.7%) nasal resistance and higher (∼2.8 times) cross-sectional areas compared to healthy controls (both p < 0.001). Despite inferior turbinate reductions, CFD analysis demonstrated that ENS patients had increased airflow concentrated in the middle meatus region (66.5% ± 18.3%) compared to healthy controls (49.9% ± 15.1%, p < 0.0001). Significantly less airflow (25.8% ± 17.6%) and lower peak wall shear stress (WSS) (0.58 ± 0.24 Pa) were found in the inferior meatus (vs healthy: 36.5% ± 15.9%; 1.18 ± 0.81 Pa, both p < 0.05), with the latter significantly correlated with the symptom scores of ENS6Q (r = -0.398, p = 0.003). Item-wise, complaints of "suffocation" and "nose feels too open" were also found to be significantly correlated with peak WSS around the inferior turbinate (r = -0.295, p = 0.031; and r = -0.388, p = 0.004, respectively). These correlations were all negative, indicating that less air-mucosal stimulations resulted in worse symptom scores. ENS patients (n = 12) also had impaired menthol LDT when compared to healthy controls (p < 0.0001).ConclusionThis is the first CFD examination of nasal aerodynamics in a large cohort of ENS patients. The results indicated that a combination of loss of neural sensitivity and poorer inferior air-mucosal stimulation may potentially lead to ENS symptomology.

Dataset Information

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

Publications

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

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