Dataset Information

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

ABSTRACT:

Background

Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders.

New method

An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8) and control mice (no hypoxia, n = 7) were handled in the same manner and their hippocampal brain regions compared by histology.

Results

The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1) P <0.001; cornu ammonis 3 (CA3) P <0.001; and dentate gyrus (DG) P = 0.023). In both, control and hypoxic conditions, there was a significantly higher number of apoptotic neurons in the DG compared to the CA1 and CA3 subfields (P <0.001).

Conclusion

The new design of a hypoxic chamber provides a fast, adjustable and reliable model of obstructive sleep apnea, which was validated by apoptosis of hippocampal neurons.

SUBMITTER: Polsek D

PROVIDER: S-EPMC5376321 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

Polšek Dora D Bago Marcel M Živaljić Marija M Rosenzweig Ivana I Lacza Zsombor Z Gajović Srećko S

PloS one 20170331 3

<h4>Background</h4>Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders.<h4 ...[more]

PMID: 28362813

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Project description:BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) could cause systematic inflammation including pulmonary inflammatory response, whereas the influence of OSAHS in pulmonary clearance ability remains unknown. The main pathophysiological feature of OSAHS is chronic intermittent hypoxia (CIH). The goal of this study is to clarify the airway clearance of particulate matter (PM) in CIH mice, and to explore the potential mechanism.MethodsBalb/c mice were divided into a CIH group and a control group, exposed to intermittent hypoxia and air chamber, respectively. A radioactive probe, 99mTc labeled PM, was endotracheally inserted into the mice at 10 mg/kg, with a starting dose of 800 μCi. The change of radioactive dose reserved in the lung was observed using single-photon emission computed tomography/computed tomography (SPECT/CT) and reconstructed data were analyzed. Special airway resistance (sRaw) of mice was measured by non-invasive airway mechanics sites. Lung resistive load (RL), elastic resistance, and compliance were measured by a multichannel physiological signal system. Lung injury was judged by hematoxylin-eosin staining and histologic score. Change in mucus secretion was determined using periodic acid-Schiff staining and enzyme-linked immunosorbent assay. Fresh lung tissue was used for real-time polymerase chain reaction and western blot analysis to explore related change of inflammation and signaling molecules and potential mechanical pathway.ResultsMice in the CIH group had higher PM radioactive deposit than the control group (93.37±3.44 μCi vs. 65.98±2.61 μCi). The average radiation dose in the lung was elevated (0.0005 μCi/mm3 vs. 0.0001383 μCi/mm3). Mice in the CIH group have higher value of sRaw, RL, and elastic resistance, whereas pulmonary compliance decreased compared to the control group (2.13±0.29 mL/cmH2O vs. 5.37±1.02 mL/cmH2O). The CIH group showed a higher histopathological score. Several genes associated with mucin secretion such as chemokine (C-X-C motif) ligand 1 (CXCL1), Clara Cell Secretory Protein 16 (CC16), macrophage inflammatory protein 2 (MIP-2), chloride channel regulator 1 (Gob5), and mucin 5AC (MUC5AC) showed elevated expression. Phosphatidylinostol-3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) pathway was activated in the CIH group.ConclusionsCIH decreased pulmonary clearance of PM and increased lung airway resistance, which may be related to inflammatory response and mucus hypersecretion in the lung.

Dataset Information

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

Background

New method

Results

Conclusion

Publications

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

Similar Datasets

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