Maintenance of systemic immune functions prevents accelerated presbycusis

Iwai, Hiroshi; Baba, Susumu; Omae, Mariko; Lee, Shinryu; Yamashita, Toshio; Ikehara, Susumu

doi:10.1016/j.brainres.2008.02.069

Cited by 28 publications

(24 citation statements)

References 40 publications

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“…We demonstrated that the hearing impairment and cochlear pathology in MRL/lpr mice can be overcome by allogeneic bone marrow transplantation, replacing the perturbed immune system of the recipients with a new immune system reconstituted by allogeneic HSCs (Iwai et al, 2005(Iwai et al, , 2008. We also demonstrated inhibited development of AHL in SAMP1 mice following inoculation of young syngeneic splenocytes (Iwai et al, 2008).…”

Section: Introductionmentioning

confidence: 83%

“…Thymectomy induces an imbalance between lymphocytes, macrophages, and cytokines, which induces neurotransmitter and neuroendocrine changes, and memory disturbance (Song, 2002). The inner ear is also regulated by systemic immunocompetent cells, including T cells and macrophages, which are supplied through the blood-inner ear barrier similar to the blood-brain barrier (Juhn, 1981) and are associated with local inflammation and restoration (Cserr and Knopf, 1992;Bhave et al, 1998;Iwai et al, 1999Iwai et al, , 2008Hashimoto et al, 2005). However, little is known about the cellular and molecular mechanisms regarding which systemic immunocompetent cell(s) and the gene(s) play a central role in the interrelationship with hearing functions and maintenance of auditory neurons in the cochlea.…”

Section: Discussionmentioning

confidence: 99%

“…Three sections were randomly selected from these mid-modiolar sections for each animal, and the nuclei of SGCs in the apical, middle, or basal turn of the cochlea were quantified, using Lumina Vision® Software (Mitani Corp., Fukui, Japan). The absolute density value was normalized for 10,000 μm 2 , as previously described (Miller et al, 1997;Iwai et al, 2008) and presented as the mean ± SD. Statistical analyses were performed by Student's t-test.…”

Section: Histopathologymentioning

confidence: 99%

“…The local inner ear immunity is part of the overall systemic response and can lead to cochlear degeneration and hearing loss (Cserr and Knopf, 1992;Iwai et al, 1999Iwai et al, , 2008Hashimoto et al, 2005;Tra et al, 2011). Of the animal models of presbycusis, the senescenceassociated mouse type 1 (SAMP1), a murine inbred strain, with a genetic background of AKR mice without senescence-prone features (Saitoh et al, 1994;Zheng et al, 1999;Liu and Kimura, 2007), shows early occurrence of thymic involution and accelerated dysfunction of immunocompetent cells, particularly T cells Liu and Kimura, 2007), followed by accelerated hearing impairment with degeneration of SGCs .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4+ T cells

Iwai

Inaba

2012

Journal of Neuroimmunology

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Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Histopathologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4+ T cells

Iwai

Inaba

2012

Journal of Neuroimmunology

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“…Although the etiologies of early-onset hereditary hearing loss are heterogeneous [1,4], the majority of cases are nonsyndromic and sensorineural (i.e., arise through the loss of auditory hair cells and/or neurons; [2,5]). As the regenerative capacity of the mammalian cochlea is severely limited, one approach currently being explored to treat hearing loss is the transplantation of endogenous stem cells [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

et al. 2011

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Transplantation of exogenous stem cells has been proposed as a treatment to prevent or reverse sensorineural hearing loss. Here, we investigate the effects of transplantation of adult human olfactory mucosa-derived stem cells on auditory function in A/J mice, a strain exhibiting early-onset progressive sensorineural hearing loss. Recent evidence indicates that these stem cells exhibit multipotency in transplantation settings and may represent a subtype of mesenchymal stem cell. Olfactory stem cells were injected into the cochleae of A/J mice via a lateral wall cochleostomy during the time period in which hearing loss first becomes apparent. Changes in auditory function were assessed 1 month after transplantation and compared against animals that received sham injections. Hearing threshold levels in stem cell-transplanted mice were found to be significantly lower than those of sham-injected mice (p < .05) for both click and pure tone stimuli. Transplanted cells survived within the perilymphatic compartments but did not integrate into cochlear tissues. These results indicate that transplantation of adult human olfactory mucosa-derived stem cells can help preserve auditory function during early-onset progressive sensorineural hearing loss. STEM CELLS 2011;29:670-677 Disclosure of potential conflicts of interest is found at the end of this article.

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Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

Chai

Yang

et al. 2021

The Laryngoscope

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Objectives/Hypothesis Lipopolysaccharide (LPS), a key component of bacterial endotoxins, activates macrophages and triggers the release of inflammatory cytokines in mammalian tissues. Recent studies have shown that intratympanic injection of LPS simulates acute otitis media (AOM) and results in morphological and functional changes in the inner ear. Here we established an AOM mouse model with LPS to investigate the uptake of ototoxic gentamicin in the inner ear, and elucidated the underlying mechanism by focusing on cochlear inflammation as a result of AOM. Study Design Preclinical rodent animal model. Methods Fluorescently tagged gentamicin (GTTR) was systemically administered to mice with AOM. Iba1‐positive macrophage morphology and inner ear cytokine profile were evaluated by immunofluorescence technique and a mouse cytokine array kit, respectively. Results We observed characteristic symptoms of AOM in the LPS‐treated ears with elevated hearing thresholds indicating a conductive hearing loss. More importantly, the LPS‐induced AOM activated cochlear inflammatory responses, manifested by macrophage infiltration, particularly in the organ of Corti and the spiral ligament, in addition to the up‐regulation of proinflammatory cytokines. Meanwhile, GTTR uptake in the stria vascularis and sensory hair cells from all the LPS‐treated ears was significantly enhanced at 24, 48, and 72‐hour post‐treatment, as the most prominent enhancement was observed in the 48‐hour group. Conclusion In summary, this study suggests that the pathological cochlea is more susceptible to ototoxic drugs, including aminoglycosides, and justified the clinical concern of aminoglycoside ototoxicity in the AOM treatment. Laryngoscope, 131:E2573–E2582, 2021

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Maintenance of systemic immune functions prevents accelerated presbycusis

Cited by 28 publications

References 40 publications

Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4+ T cells

Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4+ T cells

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

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