scholarly journals Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function

2015 ◽  
Vol 233 (6) ◽  
pp. 1825-1835 ◽  
Author(s):  
Patrick A. Armstrong ◽  
Scott J. Wood ◽  
Naoki Shimizu ◽  
Kael Kuster ◽  
Adrian Perachio ◽  
...  
Author(s):  
Yue Zhang ◽  
Jamie Soper ◽  
Christine M. Lohse ◽  
Scott D.Z. Eggers ◽  
Kenton R. Kaufman ◽  
...  

Abstract Background How significant asymmetries in otolith organ function in the presence of symmetrical and asymmetrical semicircular canal function influence skull vibration-induced nystagmus testing (SVINT) has not been well described. Purpose The aim of the study is to examine the agreement between SVINT and caloric testing, ocular vestibular-evoked myogenic potentials (oVEMP), and cervical vestibular-evoked myogenic potentials (cVEMP) for detecting asymmetric vestibular function. Research Design This is a retrospective study of patients presenting with the chief complaint of vertigo, dizziness, or imbalance. Study Sample A total of 812 patients were studied with a median age at testing of 59 years (interquartile range 46–70; range 18–93) and included 475 (59%) women. Intervention Either the monothermal warm caloric test or alternate binaural bithermal caloric test, oVEMP, and cVEMP tests were administered to all patients. All patients underwent the SVINT prior to vestibular laboratory testing. Data Collection and Analysis Agreement between tests categorized as normal versus abnormal was summarized using percent concordance (PC). Sensitivity and specificity values were calculated for SVINT compared with other tests of vestibular function. Results There was higher agreement between ipsilateral and contralateral SVINT with the caloric test (PC = 80% and 81%, respectively) compared with oVEMP (PC = 63% and 64%, respectively) and cVEMP (PC = 76% and 78%, respectively). Ipsilateral and contralateral SVINT showed higher sensitivity for the caloric test (sensitivity = 47% and 36%, respectively) compared with oVEMP (sensitivity = 26% and 21%, respectively), or cVEMP (sensitivity = 33% vs. 27%, respectively). Specificity of SVINT was high (>80%) for all assessments of vestibular function. Conclusion The presence of SVIN is a useful indicator of the asymmetry of vestibular function between the two ears when making judgments about semicircular canal asymmetry but is less sensitive to asymmetries in otolith organ function.


2005 ◽  
Vol 64 (6) ◽  
pp. 479-483 ◽  
Author(s):  
Nobuya Fujita ◽  
Toshiaki Yamanaka ◽  
Hideyuki Okamoto ◽  
Takayuki Murai ◽  
Hiroshi Hosoi

Author(s):  
Robert B. Silver ◽  
Anthony P. Reeves ◽  
Antionette Steinacker ◽  
Stephen M. Highstein

2012 ◽  
Vol 117 (2) ◽  
pp. 329-338 ◽  
Author(s):  
Willem-Jan M. Schellekens ◽  
Hieronymus W. H. van Hees ◽  
Michiel Vaneker ◽  
Marianne Linkels ◽  
P. N. Richard Dekhuijzen ◽  
...  

Background Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Methods Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Results Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Conclusion Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.


2012 ◽  
Vol 303 (9) ◽  
pp. L748-L757 ◽  
Author(s):  
Chang Hyeok An ◽  
Xiao Mei Wang ◽  
Hilaire C. Lam ◽  
Emeka Ifedigbo ◽  
George R. Washko ◽  
...  

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ ( Tlr4-mutated) mice and C57BL/10ScNJ ( Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.


2019 ◽  
Author(s):  
Shuang Shen ◽  
Fei Zhao ◽  
Zhaoyue Chen ◽  
Qingyin Zheng ◽  
Shen Yu ◽  
...  

AbstractThe aim of this study was to develop a finite element (FE) model of bilateral human semicircular canals (SCCs) in order to simulate and analyze the complex fluid-structural interaction between the endolymph and cupulae by calculating the degree of cupular expansion and the cupular deflection. The results showed that cupular deflection responses were consistent with Ewald’s II law, whereas each pair of bilateral cupulae simultaneously expanded or compressed to the same degree. In addition, both the degree of cupular expansion and cupular deflection can be expressed as the solution of forced oscillation during head sinusoidal rotation, and the amplitude of cupular expansion was approximately two times greater than that of cupular deflection. Regarding the amplitude-frequency and phase-frequency characteristics, the amplitude ratios among the horizontal semicircular canal (HC) cupular expansion, the anterior semicircular canal (AC) cupular expansion, and the posterior semicircular canal (PC) cupular expansion was constant at 1:0.82:1.62, and the phase differences among them were constant at 0 or 180 degrees at the frequencies of 0.5 to 6 Hz. However, both the amplitude ratio and the phase differencies of the cupular deflection incresed nonlinearly with the increase of frequency and tended to be constant at the frequency band between 2 and 6 Hz. The results indicate that the responses of cupular expansion might only be related to the mass and rigidity of three cupulae and the endolymph, but the responses of cupular deflection are related to the mass, rigidity, or damping of them, and these physical properties would be affected by vestibular dysfunction. Therefore, both the degree of cupular expansion and cupular deflection should be considered important mechanical variables for induced neural signals. Such a numerical model can be further built to provide a useful theoretical approach for exploring the biomechanical nature underlying vestibular dysfunction.Statement of significanceBy taking the advantage of the torsional pendulum model and the FE model, a healthy human vestibular SCCs was developed to investigate the angular motion in association with SCC function. As a result, the responses of cupular expansion and deflection during head horizontal sinusoidal rotation were analyzed for the first time, showing quantitative correlation to the eye movement due to the vestibular ocular reflex (VOR) pathway. These responses play important roles in the cupular mechano-electrical transduction process. The significant outcome derived from this study provides a useful theoretical approach for further exploring the biomechanical nature underlying vestibular dysfunction.


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