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Daniel C. Marcus - One of the best experts on this subject based on the ideXlab platform.
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The gastric H,K-ATPase in Stria Vascularis contributes to pH regulation of cochlear endolymph but not to K secretion
BMC Physiology, 2016Co-Authors: Hiromitsu Miyazaki, Philine Wangemann, Daniel C. MarcusAbstract:Background Disturbance of acid–base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid–base transporters in Stria Vascularis. Results We directly measured acid flux in vitro from the apical side of isolated Stria Vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe. Acid efflux that depended on metabolism and ion transport was observed from the apical side of Stria Vascularis. The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694, b) by inhibition of Na,2Cl,K-cotransporter (NKCC1) by bumetanide, and c) by the likely inhibition of HCO_3/anion exchange by DIDS. By contrast, the acid flux was increased by inhibition of gastric H,K-ATPase (SCH28080) but was not affected by an inhibitor of vH-ATPase (bafilomycin). K flux from Stria Vascularis was reduced less than 5 % by SCH28080. Conclusions These observations suggest that Stria Vascularis may be an important site of control of cochlear acid–base balance and demonstrate a functional role of several acid–base transporters in Stria Vascularis, including basolateral H,K-ATPase and apical Na,H-exchange. Previous suggestions that H secretion is mediated by an apical vH-ATPase and that basolateral H,K-ATPase contributes importantly to K secretion in Stria Vascularis are not supported. These results advance our understanding of inner ear acid–base balance and provide a stronger basis to interpret the etiology of genetic and pharmacologic cochlear dysfunctions that are influenced by endolymphatic pH.
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The gastric H,K-ATPase in Stria Vascularis contributes to pH regulation of cochlear endolymph but not to K secretion
BMC physiology, 2016Co-Authors: Hiromitsu Miyazaki, Philine Wangemann, Daniel C. MarcusAbstract:Disturbance of acid–base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid–base transporters in Stria Vascularis. We directly measured acid flux in vitro from the apical side of isolated Stria Vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe. Acid efflux that depended on metabolism and ion transport was observed from the apical side of Stria Vascularis. The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694, b) by inhibition of Na,2Cl,K-cotransporter (NKCC1) by bumetanide, and c) by the likely inhibition of HCO3/anion exchange by DIDS. By contrast, the acid flux was increased by inhibition of gastric H,K-ATPase (SCH28080) but was not affected by an inhibitor of vH-ATPase (bafilomycin). K flux from Stria Vascularis was reduced less than 5 % by SCH28080. These observations suggest that Stria Vascularis may be an important site of control of cochlear acid–base balance and demonstrate a functional role of several acid–base transporters in Stria Vascularis, including basolateral H,K-ATPase and apical Na,H-exchange. Previous suggestions that H secretion is mediated by an apical vH-ATPase and that basolateral H,K-ATPase contributes importantly to K secretion in Stria Vascularis are not supported. These results advance our understanding of inner ear acid–base balance and provide a stronger basis to interpret the etiology of genetic and pharmacologic cochlear dysfunctions that are influenced by endolymphatic pH.
Philine Wangemann - One of the best experts on this subject based on the ideXlab platform.
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The gastric H,K-ATPase in Stria Vascularis contributes to pH regulation of cochlear endolymph but not to K secretion
BMC physiology, 2016Co-Authors: Hiromitsu Miyazaki, Philine Wangemann, Daniel C. MarcusAbstract:Disturbance of acid–base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid–base transporters in Stria Vascularis. We directly measured acid flux in vitro from the apical side of isolated Stria Vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe. Acid efflux that depended on metabolism and ion transport was observed from the apical side of Stria Vascularis. The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694, b) by inhibition of Na,2Cl,K-cotransporter (NKCC1) by bumetanide, and c) by the likely inhibition of HCO3/anion exchange by DIDS. By contrast, the acid flux was increased by inhibition of gastric H,K-ATPase (SCH28080) but was not affected by an inhibitor of vH-ATPase (bafilomycin). K flux from Stria Vascularis was reduced less than 5 % by SCH28080. These observations suggest that Stria Vascularis may be an important site of control of cochlear acid–base balance and demonstrate a functional role of several acid–base transporters in Stria Vascularis, including basolateral H,K-ATPase and apical Na,H-exchange. Previous suggestions that H secretion is mediated by an apical vH-ATPase and that basolateral H,K-ATPase contributes importantly to K secretion in Stria Vascularis are not supported. These results advance our understanding of inner ear acid–base balance and provide a stronger basis to interpret the etiology of genetic and pharmacologic cochlear dysfunctions that are influenced by endolymphatic pH.
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The gastric H,K-ATPase in Stria Vascularis contributes to pH regulation of cochlear endolymph but not to K secretion
BMC Physiology, 2016Co-Authors: Hiromitsu Miyazaki, Philine Wangemann, Daniel C. MarcusAbstract:Background Disturbance of acid–base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid–base transporters in Stria Vascularis. Results We directly measured acid flux in vitro from the apical side of isolated Stria Vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe. Acid efflux that depended on metabolism and ion transport was observed from the apical side of Stria Vascularis. The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694, b) by inhibition of Na,2Cl,K-cotransporter (NKCC1) by bumetanide, and c) by the likely inhibition of HCO_3/anion exchange by DIDS. By contrast, the acid flux was increased by inhibition of gastric H,K-ATPase (SCH28080) but was not affected by an inhibitor of vH-ATPase (bafilomycin). K flux from Stria Vascularis was reduced less than 5 % by SCH28080. Conclusions These observations suggest that Stria Vascularis may be an important site of control of cochlear acid–base balance and demonstrate a functional role of several acid–base transporters in Stria Vascularis, including basolateral H,K-ATPase and apical Na,H-exchange. Previous suggestions that H secretion is mediated by an apical vH-ATPase and that basolateral H,K-ATPase contributes importantly to K secretion in Stria Vascularis are not supported. These results advance our understanding of inner ear acid–base balance and provide a stronger basis to interpret the etiology of genetic and pharmacologic cochlear dysfunctions that are influenced by endolymphatic pH.
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Macrophage invasion contributes to degeneration of Stria Vascularis in Pendred syndrome mouse model.
BMC medicine, 2006Co-Authors: Sairam V. Jabba, Alisha M. Oelke, Ruchira Singh, Rajanikanth J Maganti, Sherry D. Fleming, Susan M. Wall, Lorraine A. Everett, Eric D. Green, Philine WangemannAbstract:Pendred syndrome, an autosomal-recessive disorder characterized by deafness and goiter, is caused by a mutation of SLC26A4, which codes for the anion exchanger pendrin. We investigated the relationship between pendrin expression and deafness using mice that have (Slc26a4+/+ or Slc26a4+/-) or lack (Slc26a4-/-) a complete Slc26a4 gene. Previously, we reported that Stria Vascularis of adult Slc26a4-/- mice is hyperpigmented and that marginal cells appear disorganized. Here we determine the time course of hyperpigmentation and marginal cell disorganization, and test the hypothesis that inflammation contributes to this tissue degeneration. Slc26a4-/- and age-matched control (Slc26a4+/+ or Slc26a4+/-) mice were studied at four postnatal (P) developmental stages: before and after the age that marks the onset of hearing (P10 and P15, respectively), after weaning (P28-41) and adult (P74-170). Degeneration and hyperpigmentation Stria Vascularis was evaluated by confocal microscopy. Gene expression in Stria Vascularis was analyzed by microarray and quantitative RT-PCR. In addition, the expression of a select group of genes was quantified in spiral ligament, spleen and liver to evaluate whether expression changes seen in Stria Vascularis are specific for Stria Vascularis or systemic in nature. Degeneration of Stria Vascularis defined as hyperpigmentation and marginal cells disorganization was not seen at P10 or P15, but occurred after weaning and was associated with staining for CD68, a marker for macrophages. Marginal cells in Slc26a4-/-, however, had a larger apical surface area at P10 and P15. No difference in the expression of Lyzs, C3 and Cd45 was found in Stria Vascularis of P15 Slc26a4+/- and Slc26a4-/- mice. However, differences in expression were found after weaning and in adult mice. No difference in the expression of markers for acute inflammation, including Il1a, Il6, Il12a, Nos2 and Nos3 were found at P15, after weaning or in adults. The expression of macrophage markers including Ptprc (= Cd45), Cd68, Cd83, Lyzs, Lgals3 (= Mac2 antigen), Msr2, Cathepsins B, S, and K (Ctsb, Ctss, Ctsk) and complement components C1r, C3 and C4 was significantly increased in Stria Vascularis of adult Slc26a4-/- mice compared to Slc26a4+/+ mice. Expression of macrophage markers Cd45 and Cd84 and complement components C1r and C3 was increased in Stria Vascularis but not in spiral ligament, liver or spleen of Slc26a4-/- compared to Slc26a4+/- mice. The expression of Lyzs was increased in Stria Vascularis and spiral ligament but not in liver or spleen. The data demonstrate that hyperpigmentation of Stria Vascularis and marginal cell reorganization in Slc26a4-/- mice occur after weaning, coinciding with an invasion of macrophages. The data suggest that macrophage invasion contributes to tissue degeneration in Stria Vascularis, and that macrophage invasion is restricted to Stria Vascularis and is not systemic in nature. The delayed onset of degeneration of Stria Vascularis suggests that a window of opportunity exists to restore/preserve hearing in mice and therefore possibly in humans suffering from Pendred syndrome.
Shi-ming Yang - One of the best experts on this subject based on the ideXlab platform.
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Transcript Profiles of Stria Vascularis in Models of Waardenburg Syndrome.
Neural plasticity, 2020Co-Authors: Linjun Chen, Lei Chen, Fangyuan Wang, Wei Sun, Hui Zhao, Weiju Han, Lin Wang, Shi-ming YangAbstract:Background Waardenburg syndrome is an uncommon genetic condition characterized by at least some degree of congenital hearing loss and pigmentation deficiencies. However, the genetic pathway affecting the development of Stria Vascularis is not fully illustrated. Methods The transcript profile of Stria Vascularis of Waardenburg syndrome was studied using Mitf-M mutant pig and mice models. Therefore, GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results There were 113 genes in tyrosine metabolism, melanin formation, and ion transportations showed significant changes in pig models and 191 genes in mice models. In addition, there were some spice's specific gene changes in the Stria Vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19, and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the Stria Vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1, and Col11a2 genes were higher, and the expression of Col8a2, Cd34, and Ncam genes were lower in the porcine models compared to mouse models. Conclusions Our data suggests that there is a significant difference on the gene expression and function between these two models.
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The morphological and functional development of the Stria Vascularis in miniature pigs
Reproduction fertility and development, 2017Co-Authors: Weiwei Guo, Lei Chen, Zhang Yan, Lili Ren, Lidong Zhao, Yu Ning, Shi-ming YangAbstract:The purpose of this study was to examine the morphological and functional development of the lateral wall of the scala media of the cochlea in miniature pigs; light and transmission electron microscopy and electrophysiology were used for this purpose. We showed that the lateral wall of the scala media of the cochlea appears at embryonic Day 21 (E21) when the cochlear duct begins to form. From E28 to E49, the lateral wall can be distinguished according to its position along the cochlea. At E56, cells in the lateral wall begin to differentiate into three different types. At E70, three cell types, marginal, intermediate and basal, can be clearly distinguished. At E91, the Stria Vascularis is adult-like and the organ of Corti is also morphologically mature. The average endocochlear potential measured from the second turn of the cochlea (at E98, postnatal Day 1 (P1), P13 and P30) was 71.4±2.5 (n=7), 78.8±1.5 (n=10), 77.3±2.3 (n=10) and 78.0±2.1 mV (n=10), respectively. Our results suggest that in miniature pigs the Stria Vascularis develops during the embryonic period, concurrent with maturation of the organ of Corti. The magnitude of the endocochlear potential reached its mature level when the Stria Vascularis was morphologically adult-like at E98. These findings provide a morphological and functional basis for future animal studies using the miniature pig model concerning the pathogenesis of various inner-ear diseases.
Mats Ulfendahl - One of the best experts on this subject based on the ideXlab platform.
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Malformation of Stria Vascularis in the developing inner ear of the German waltzing guinea pig
Cell and Tissue Research, 2007Co-Authors: Zhe Jin, Paula Mannström, Leif Järlebark, Mats UlfendahlAbstract:Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig ( gw/gw ). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner’s membrane onto the hearing organ. The embryonic Stria Vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw Stria Vascularis. A gene involved in cochlear melanocyte development, Pax3 , was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing Stria Vascularis of this type of guinea pig. Thus, malformation of the Stria Vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing Stria Vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to Stria Vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.
Dennis R. Trune - One of the best experts on this subject based on the ideXlab platform.
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breakdown of Stria Vascularis blood labyrinth barrier in c3h lpr autoimmune disease mice
Otolaryngology-Head and Neck Surgery, 1997Co-Authors: David W. Lin, Dennis R. TruneAbstract:Abstract Sensorineural hearing loss related to autoimmune disease is a well-recognized condition, although the exact pathophysiologic mechanisms remain unclear. One current theory postulates immune complex–induced interference with blood-labyrinth barrier integrity in the Stria Vascularis. The C3H/ lpr autoimmune mouse was chosen to study the permeability of capillaries in the Stria Vascularis because this mouse model has demonstrated abnormalities of the Stria Vascularis and shifts in the auditory brain stem response threshold during active disease. C3H/ lpr mice with active disease were compared with younger mice without disease, as well as age-matched C3H/HeJ control mice. The mice were injected with the tracer ferritin and examined by transmission electron microscopy to evaluate the integrity of the capillary tight junctions in the Stria Vascularis. Four of five mice with active disease were noted to have extensive leakage of ferritin into the perivascular tissues. Neither the young, disease-free autoimmune mice nor the nonautoimmune control mice demonstrated vessel leakage. Thickening of the basement membrane was also noted in the diseased animals. The results imply that active disease leads to a breakdown in the blood-endolymph barrier, which could underlie the hearing loss accompanying autoimmune and other immune diseases. (Otolaryngol Head Neck Surg 1997;117:530-4.)
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Breakdown of Stria Vascularis blood-labyrinth barrier in C3H/lpr autoimmune disease mice
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 1997Co-Authors: David W. Lin, Dennis R. TruneAbstract:Sensorineural hearing loss related to autoimmune disease is a well-recognized condition, although the exact pathophysiologic mechanisms remain unclear. One current theory postulates immune complex-induced interference with blood-labyrinth barrier integrity in the Stria Vascularis. The C3H/lpr autoimmune mouse was chosen to study the permeability of capillaries in the Stria Vascularis because this mouse model has demonstrated abnormalities of the Stria Vascularis and shifts in the auditory brain stem response threshold during active disease. C3H/lpr mice with active disease were compared with younger mice without disease, as well as age-matched C3H/HeJ control mice. The mice were injected with the tracer ferritin and examined by transmission electron microscopy to evaluate the integrity of the capillary tight junctions in the Stria Vascularis. Four of five mice with active disease were noted to have extensive leakage of ferritin into the perivascular tissues. Neither the young, disease-free autoimmune mice nor the nonautoimmune control mice demonstrated vessel leakage. Thickening of the basement membrane was also noted in the diseased animals. The results imply that active disease leads to a breakdown in the blood-endolymph barrier, which could underlie the hearing loss accompanying autoimmune and other immune diseases.
