Ultrastructural Study of the Effect of Acute Hyper- and Hypotension on the Stria Vascularis and Spiral Ligament

Sakagami, Masafumi; Sano, Masashi; Tamaki, Hiromitsu; Matsunaga, Toru

doi:10.3109/00016488309123046

Cited by 5 publications

(5 citation statements)

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“…HRP tracer permeability assay was performed in treated and control animals as per the protocol described previously (Sakagami et al, 1984) with some modifications. Briefly, mice were anaesthetized with pentobarbital and carotid was exposed after surgery.…”

Section: Methodsmentioning

confidence: 99%

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice

Kundu¹,

Munjal²,

Tyagi³

et al. 2012

Hearing Research

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More than 29 million adults in the United States have been diagnosed with hearing loss. Interestingly, elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy) is also associated with impaired hearing. However, the associated mechanism remains obscure. The collagen receptor such as discoidin domain receptor 1 and matrix metalloproteinase (MMP) play a significant role in inner ear structure and function. We hypothesize that HHcy increases hearing thresholds by compromise in inner ear vasculature resulted from impaired Hcy metabolism, increased oxidative stress, collagen IVa and collagen la turnover. The treatment with folic acid (FA) protects elevated hearing thresholds and prevents reduction in vessel density by lowering abundant collagen deposition and oxidative stress in inner ear. To test this hypothesis we employed 8 weeks old male wild type (WT), cystathionine-beta-synthase heterozygote knockout (CBS+/−) mice, WT+FA (0.0057 μg/g/day, equivalent to a 400 μg/70 kg/day human dose in drinking water); and CBS(+/−)+FA. The mice were treated for four weeks. The hearing thresholds were determined by recording the auditory brainstem responses. Integrity of vessels was analyzed by perfusion of horseradish peroxidase (HRP) tracer. Endothelial permeability was assessed, which indicated restoration of HRP leakage by FA treatment. A total Hcy level was increased in stria vascularis (SV) and spiral ligament (SL) of CBS+/− mice which was lowered by FA. Interestingly, FA treatment lowered Col IVa Immunostaining by affecting its turnover. The levels of MMP-2, -9, methylenetetrahydrofolate reductase (MTHFR) and cystathione gamma lyase (CSE) were measured by Western blot analysis. The oxidative stress was high in SV and SL of CBS+/− compared to WT however the treatment with FA lowered oxidative stress in CBS+/− mice. These data suggested that hearing loss in CBS+/− mice was primarily due to leakage in inner ear circulation, also partly by induced collagen imbalance, increase in Hey and oxidative stress in inner ear.

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Section: Methodsmentioning

confidence: 99%

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice

Kundu¹,

Munjal²,

Tyagi³

et al. 2012

Hearing Research

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“…The endothelial cells of the spiral ligament, however, are impermeable to H R P (Duvall et al 1971;Duvall and Klinker 1983;Gorgas and Jahnke 1974) and exhibit little pinocytosis. In contrast, strial endothelial cells exhibit a high degree of pinocytosis and are permeable to H R P via an endocytosis-exocytosis route (Sakagami et al 1984). Based upon morphological evidence, Jahnke (1980) has proposed that Capillaries of the stria vascularis differ further from those of the spiral ligament in that they are intraepithelial.…”

Section: Discussionmentioning

confidence: 99%

Primary culture of capillary endothelial cells from the spiral ligament and stria vascularis of bovine inner ear

et al. 1985

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Methods for isolation and culture of microvascular endothelial cells of the inner ear were devised to provide an in-vitro system for studying endothelial functions in this tissue. Capillaries from the stria vascularis and spiral ligament were treated enzymatically to free them from surrounding tissue. Contamination by extraneous tissue was minimized by banding capillary segments in Percoll gradients and culture in plasma-derived serum on a fibronectin-coated substrate. Although only small amounts of inner ear tissue were available, tritiated thymidine autoradiography demonstrated that considerable growth in culture was possible. Addition of heparin and endothelial cell growth supplement to the medium enhanced proliferation. The endothelial origin of the cultured cells was confirmed by immunofluorescent demonstration of the presence of Factor VIII-related antigen and angiotensin-converting enzyme. In addition, tight junctions between cells were observed in both thin sections and platinum replicas obtained by freeze-fracture techniques. Endothelial cells from neither the stria vascularis nor the spiral ligament allowed passage of horseradish peroxidase across the monolayer during a 5-min period. However, endothelial cells from the stria vascularis exhibited a greater amount of pinocytotic activity than those of the spiral ligament, a difference that is also observed in vivo. Methods for expanding a small population of endothelial cells with retention of specialized properties into one of sufficient size for morphologic and biochemical studies have been demonstrated for the inner ear.

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“…The stria vascularis and spiral ligament were defined as integral structures for the BLaB barrier [ 175 ] recognized by Hawkins in 1960. More specific structures within the stria vascularis were defined, such as tight junctions of marginal and basal cells within the endolymph and perilymph barriers, respectively [ 176 ]. Recently, a subset of barriers within the BLaB has been proposed, consisting of five interrelated but independent membranous labyrinth barriers: the blood–endolymph barrier, blood–perilymph barrier, cerebrospinal-fluid–perilymph barrier, middle-ear–labyrinth barrier, and endolymph–perilymph barrier [ 177 ].…”

Section: Blood–labyrinth Barrier (Blab) and Blood–retinal Barrier mentioning

confidence: 99%

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

2021

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Since the 2013 Nobel Prize was awarded for the discovery of vesicle trafficking, a subgroup of nanovesicles called exosomes has been driving the research field to a new regime for understanding cellular communication. This exosome-dominated traffic control system has increased understanding of many diseases, including cancer metastasis, diabetes, and HIV. In addition to the important diagnostic role, exosomes are particularly attractive for drug delivery, due to their distinctive properties in cellular information transfer and uptake. Compared to viral and non-viral synthetic systems, the natural, cell-derived exosomes exhibit intrinsic payload and bioavailability. Most importantly, exosomes easily cross biological barriers, obstacles that continue to challenge other drug delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood–brain barrier (BBB), blood–cerebrospinal fluid barrier (BCSFB), blood–lymph barrier (BlyB), blood–air barrier (BAB), stromal barrier (SB), blood–labyrinth barrier (BLaB), blood–retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform. However, the systematic reviews summarizing such discoveries are still limited. This review covers state-of-the-art exosome research on crossing several important biological barriers with a focus on the current, accepted models used to explain the mechanisms of barrier crossing, including tight junctions. The potential to design and engineer exosomes to enhance delivery efficacy, leading to future applications in precision medicine and immunotherapy, is discussed.

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Ultrastructural Study of the Effect of Acute Hyper- and Hypotension on the Stria Vascularis and Spiral Ligament

Cited by 5 publications

References 5 publications

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice

Folic acid improves inner ear vascularization in hyperhomocysteinemic mice

Primary culture of capillary endothelial cells from the spiral ligament and stria vascularis of bovine inner ear

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

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