Dataset Information

Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier.

ABSTRACT: The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid-blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each other by tight junctions and an underlying basement membrane. In a recent study, we found that the intrastrial fluid-blood barrier also includes a large number of perivascular cells with both macrophage and melanocyte characteristics. The perivascular-resident macrophage-like melanocytes (PVM/Ms) are in close contact with vessels through cytoplasmic processes. Here we demonstrate that PVM/Ms have an important role in maintaining the integrity of the intrastrial fluid-blood barrier and hearing function. Using a cell culture-based in vitro model and a genetically induced PVM/M-depleted animal model, we show that absence of PVM/Ms increases the permeability of the intrastrial fluid-blood barrier to both low- and high-molecular-weight tracers. The increased permeability is caused by decreased expression of pigment epithelial-derived factor, which regulates expression of several tight junction-associated proteins instrumental to barrier integrity. When tested for endocochlear potential and auditory brainstem response, PVM/M-depleted animals show substantial drop in endocochlear potential with accompanying hearing loss. Our results demonstrate a critical role for PVM/Ms in regulating the permeability of the intrastrial fluid-blood barrier for establishing a normal endocochlear potential hearing threshold.

SUBMITTER: Zhang W

PROVIDER: S-EPMC3387119 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier.

Zhang Wenjing W Dai Min M Fridberger Anders A Hassan Ahmed A Degagne Jacqueline J Neng Lingling L Zhang Fei F He Wenxuan W Ren Tianying T Trune Dennis D Auer Manfred M Shi Xiaorui X

Proceedings of the National Academy of Sciences of the United States of America 20120611 26

The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid-blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each other by tight junctions and an underlying basement membrane. In a recent study, we found that the intrastrial fluid-blood barrier also includes a large number of perivascular cells w ...[more]

PMID: 22689949

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Project description:Objective: Capillaries within the inner ear form a semi-permeable barrier called the blood-labyrinth barrier that is less permeable than capillary barriers elsewhere within the human body. Dysfunction of the blood-labyrinth barrier has been proposed as a mechanism for several audio-vestibular disorders. There has been interest in using magnetic resonance imaging (MRI) with intravenous gadolinium-based contrast agents (GBCA) as a marker for the integrity of the blood labyrinth barrier in research and clinical settings. This scoping review evaluates the evidence for using intravenous gadolinium-enhanced MRI to assess the permeability of the blood-labyrinth barrier in healthy and diseased ears. Methods: A systematic search was conducted of three databases: PubMed, EMBASE, CINAHL PLUS. Studies were included that used GBCA to study the inner ear and permeability of the blood-labyrinth barrier. Data was collected on MRI protocols used and inner ear enhancement patterns of healthy and diseased ears in both human and animal studies. Results: The search yielded 14 studies in animals and 53 studies in humans. In healthy animal and human inner ears, contrast-enhanced MRI demonstrated gradual increase in inner ear signal intensity over time that was limited to the perilymph. Signal intensity peaked at 100 min in rodents and 4 h in humans. Compared to controls, patients with idiopathic sudden sensorineural hearing loss and otosclerosis had increased signal intensity both before and shortly after GBCA injection. In patients with Ménière's disease and vestibular schwannoma, studies reported increased signal at 4 h, compared to controls. Quality assessment of included studies determined that all the studies lacked sample size justification and many lacked adequate control groups or blinded assessors of MRI. Conclusions: The included studies provided convincing evidence that gadolinium crosses the blood-labyrinth barrier in healthy ears and more rapidly in some diseased ears. The timing of increased signal differs by disease. There was a lack of evidence that these findings indicate general permeability of the blood-labyrinth barrier. Future studies with consistent and rigorous methods are needed to investigate the relationship between gadolinium uptake and assessments of inner ear function and to better determine whether signal enhancement indicates permeability for molecules other than gadolinium.

Dataset Information

Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier.

Publications

Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier.

Similar Datasets

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