Carcinomatous Encephalomyelitis with Auditory and Vestibular Manifestations

1976 ◽  
Vol 85 (1) ◽  
pp. 120-126 ◽  
Author(s):  
Trevor McGill
Keyword(s):  
Cochlear Nucleus ◽  
Stria Vascularis ◽  
Neuronal Loss ◽  
Organ Of Corti ◽  
Sensory Neuropathy ◽  
Pathological Study ◽  
Striking Change ◽  
Oat Cell Carcinoma ◽  
Cochlear Neurons ◽  
Microglial Response

A clinical and pathological study of carcinomatous encephalomyelitis is presented. Attention is drawn to the various types of nonmetastatic paraneoplastic syndromes and their particular association with oat cell carcinoma of the lung. The feature of special interest in this study is the onset with otologic symptoms, sudden deafness in the left ear and vertigo, at a time when the neoplastic basis for the disease was not clinically evident. The most striking change in the left temporal bone is the almost total loss of cochlear neurons in Rosenthal's canal and degeneration of both divisions of the vestibular nerve. The organ of Corti and stria vascularis are normal throughout the cochlear duct. The vestibular sense organs are normal. The left cochlear nucleus is devoid of neurons, this neuronal loss is accompanied by a well developed astrocytic and microglial response similar to that in the medulla and spinal cord. This represents a carcinomatous sensory neuropathy involving the left VIII nerve with simultaneous involvement of the left cochlear nucleus. The pathogenesis of this condition still defies explanation, but there are some insights in the autoimmune sector.

scholarly journals Distribution of aspartate and glutamate in cochlear nucleus (CN) following destruction of organ of Corti (OC)

1980 ◽  
Vol 67 (S1) ◽  
pp. S77-S77 ◽  
Author(s):  
R. Thalmann ◽  
T. H. Comegys ◽  
I. Thalmann ◽  
D. B. Webster
Keyword(s):  
Cochlear Nucleus ◽  
Organ Of Corti

scholarly journals Expression of Gap Junction Protein Connexin43 in the Adult Rat Cochlea: Comparison with Connexin26

2003 ◽  
Vol 51 (7) ◽  
pp. 903-912 ◽  
Author(s):  
Toshihiro Suzuki ◽  
Tetsuro Takamatsu ◽  
Masahito Oyamada
Keyword(s):  
Gap Junction ◽  
Stria Vascularis ◽  
Three Dimensional ◽  
Organ Of Corti ◽  
Structural Difference ◽  
Lateral Wall ◽  
Spiral Ligament ◽  
Adult Rat ◽  
Junction Protein ◽  
Rat Cochlea

To elucidate whether the two different gap junction proteins connexin43 (Cx43) and connexin26 (Cx26) are expressed and localized in a similar manner in the adult rat cochlea, we performed three-dimensional confocal microscopy using cryosections and surface preparations. In the cochlear lateral wall, Cx43-positive spots were localized mainly in the stria vascularis and only a few spots were present in the spiral ligament, whereas Cx26-positive spots were detected in both the stria vascularis and the spiral ligament. In the spiral limbus, Cx43 was widely distributed, whereas Cx26 was more concentrated on the side facing the scala vestibuli and in the basal portion. In the organ of Corti, Cx43-positive spots were present between the supporting cells but they were fewer and much smaller than those of Cx26. These data demonstrated distinct differences between Cx43 and Cx26 in expression and localization in the cochlea. In addition, the area of overlap of zonula occludens-1 (ZO-1) immunolabeling with Cx43-positive spots was small, whereas it was fairly large with Cx26-positive spots in the cochlear lateral wall, suggesting that the differences are not associated with the structural difference between carboxyl terminals, i.e., those of Cx43 possess sequences for binding to ZO-1, whereas those of Cx26 lack these binding sequences.

scholarly journals Induction of Redox-Active Gene Expression by CoCl2 Ameliorates Oxidative Stress-Mediated Injury of Murine Auditory Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 399 ◽  
Author(s):  
Jhang Ho Pak ◽  
Junyeong Yi ◽  
Sujin Ryu ◽  
In Ki Kim ◽  
Jung-Woong Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Hypoxia Inducible Factor ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Redox Active

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The present study was designed to understand the preconditioning effect of CoCl2 on oxidative stress-mediated cytotoxicity. Treatment of auditory cells with CoCl2 promoted cell proliferation, with increases in the expressions of two redox-active transcription factors (hypoxia-inducible factor 1α, HIF-1α, nuclear factor erythroid 2-related factor 2; Nrf-2) and an antioxidant enzyme (peroxiredoxin 6, Prdx6). Hydrogen peroxide treatment resulted in the induction of cell death and reduction of these protein expressions, reversed by pretreatment with CoCl2. Knockdown of HIF-1α or Nrf-2 attenuated the preconditioning effect of CoCl2. Luciferase reporter analysis with a Prdx6 promoter revealed transactivation of Prdx6 expression by HIF-1α and Nrf-2. The intense immunoreactivities of HIF-1α, Nrf-2, and Prdx6 in the organ of Corti (OC), spiral ganglion cells (SGC), and stria vascularis (SV) of the cochlea in CoCl2-injected mice suggested CoCl2-induced activation of HIF-1α, Nrf-2, and Prdx6 in vivo. Therefore, we revealed that the protective effect of CoCl2 is achieved through distinctive signaling mechanisms involving HIF-1α, Nrf-2, and Prdx6.

Cochlear Neuronal Loss as Determined by Use of a Neurofilament Protein Antibody in Cases of Bilateral Profound Deafness

1998 ◽  
Vol 77 (8) ◽  
pp. 662-668
Author(s):  
Yukiko Iino ◽  
Taku Komiya ◽  
Tomoko Fujii ◽  
Yoshinori Nakamoto ◽  
Satoru Koyama ◽  
...  
Keyword(s):  
Measles Virus ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Neuronal Loss ◽  
Organ Of Corti ◽  
Afferent Neurons ◽  
Neurofilament Protein ◽  
Efferent Neurons ◽  
Temporal Bones ◽  
Bilateral Deafness

The temporal bones of two patients with profound bilateral deafness from infancy were studied immunohistochemically, using a neurofilament protein antibody to detect the cochlear neuronal elements. One patient exhibited Mondini dysplasia of the inner ear, with the organ of Corti almost completely deteriorated. The other patient is the first reported case involving complete aplasia of the organ of Corti in all turns. In both cases, the immunohistochemical staining clearly revealed a severe reduction in the number of afferent neurons, such as dendrites, spiral ganglion cells and cochlear axons. The number of efferent spiral bundles in the osseous spiral lamina and intraganglionic portion also decreased in parallel with the reduction in the number of cochlear afferent neurons. Our results are inconsistent with previously reported cases of presbycusis and acquired deafness induced by the measles virus, in which efferent neurons were preserved while afferent neurons degenerated. The loss of both the efferent and afferent neurons might be characteristics of congenital deafness.

The morphological and functional development of the stria vascularis in miniature pigs

2017 ◽  
Vol 29 (3) ◽  
pp. 585 ◽  
Author(s):  
Weiwei Guo ◽  
Haijin Yi ◽  
Zhang Yan ◽  
Lili Ren ◽  
Lei Chen ◽  
...  
Keyword(s):  
Animal Studies ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Lateral Wall ◽  
Cell Types ◽  
Endocochlear Potential ◽  
Miniature Pigs ◽  
Functional Development ◽  
Transmission Electron ◽  
Different Types

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.

scholarly journals Otic Pathology of Caprine β-Mannosidosis

1988 ◽  
Vol 25 (6) ◽  
pp. 437-442 ◽  
Author(s):  
J. A. Render ◽  
K. L. Lovell ◽  
M. Z. Jones
Keyword(s):  
Storage Disease ◽  
Stria Vascularis ◽  
Genetic Disorder ◽  
Spiral Ganglion ◽  
Clinical Signs ◽  
Organ Of Corti ◽  
Scala Tympani ◽  
Electron Microscopic ◽  
Middle Ear Mucosa ◽  
Cochlear Hair Cells

Caprine β-mannosidosis is an autosomal recessive defect of glycoprotein catabolism with a deficiency of tissue and plasma β-mannosidase activity and tissue accumulation of oligosaccharides within lysosomes. This rapidly fatal genetic disorder of Nubian goats is expressed at birth by a variety of clinical signs including deafness. Affected goats had folded pinnas, and the tympanic cavity was decreased due to multiple, polypoid projections of bone covered by middle ear mucosa which obstructed the view of the cochlear promontory. Numerous cells of the cochlear duct including mesothelial and epithelial cells of Reissner's membrane, mesothelial cells lining the scala tympani, cells of the stria vascularis, numerous supportive cells of the organ of Corti, cochlear hair cells, endothelial cells, perithelial cells, fibroblasts, macrophages, and neurons of the spiral ganglion contained numerous nonstaining intracytoplasmic vacuoles which resulted in distention of affected cells and caused thickening of involved structures. Ultrastructurally, the vacuoles were membrane-bound and consistent with lysosomes. Vacuolated cells were desquamated into the scala vestibuli and scala tympani. This is one of few reports describing light and electron microscopic otic alterations of a storage disease. Goats with β-mannosidosis appear to be good models of hearing loss in patients with storage disease.

Development of mammalian endocochlear potential: normal ontogeny and effects of anoxia

1986 ◽  
Vol 250 (3) ◽  
pp. R493-R498 ◽  
Author(s):  
N. K. Woolf ◽  
A. F. Ryan ◽  
J. P. Harris
Keyword(s):  
Glucose Metabolism ◽  
Mongolian Gerbil ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Endocochlear Potential ◽  
Cochlear Microphonic ◽  
Cochlear Hair Cells ◽  
Apical Membranes ◽  
Cochlear Microphonic Potential

The development of the positive endocochlear potential (EP), the negative anoxic EP, and the organ of Corti potential were measured at various postnatal ages in the Mongolian gerbil, beginning at 8 days after birth (DAB). The organ of Corti potential (OCP) was present at 8 DAB but averaged 21% less than the adult value. OCP increased regularly with age, reaching adult values of -90 mV by 14 DAB. The positive EP was first observed at 10 DAB, at which age it averaged only 2-3 mV. This potential increased monotonically between 10 and 20 DAB, by which time it had reached the adult value of 75 mV. Anoxia did not result in a negative EP until 12 DAB, at which age this potential averaged -7 mV. The negative anoxic EP matured more rapidly than the positive EP, achieving the adult value of 40 mV by 18 DAB. During development the positive EP appeared to closely parallel the maturation of glucose metabolism in the stria vascularis. The negative anoxic EP was more closely related temporally to the development of cochlear microphonic potential (CM) thresholds. It is hypothesized that changes which occur between 10 and 16 DAB in the apical membranes of the cochlear hair cells contribute to the maturation of both CM and the negative anoxic EP.

scholarly journals Caffeine Induces Autophagy and Apoptosis in Auditory Hair Cells via the SGK1/HIF-1α Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaomin Tang ◽  
Yuxuan Sun ◽  
Chenyu Xu ◽  
Xiaotao Guo ◽  
Jiaqiang Sun ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ganglion Neurons ◽  
Auditory Hair Cells ◽  
Qrt Pcr ◽  
Ganglion Neurons

Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.

scholarly journals Met/HGFR triggers detrimental reactive microglia in TBI

2021 ◽  
Author(s):  
Rida Rehman ◽  
Michael Miller ◽  
Sruthi Sankari Krishnamurthy ◽  
Jacob Kjell ◽  
Lobna Elsayed ◽  
...  
Keyword(s):  
Large Scale ◽  
Temporal Dynamics ◽  
Scale Effects ◽  
Human Subjects ◽  
Neuronal Loss ◽  
Motor Dysfunction ◽  
List Type ◽  
Reactive Microglia ◽  
Molecule Inhibitor ◽  
Microglial Response

AbstractThe complexity of the signaling events, cellular responses unfolding in neuronal, glial and immune cells upon Traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We used array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then to scrutinize the large-scale effects of the perturbation of cMet/HGFR, VEGFR1 and Btk signaling by small molecules. cMet/HGFR emerged as a selective modifier of the early microglial response, and cMet/HGFR blockade prevented the induction of microglial inflammatory mediators, of reactive microglia morphology and of TBI-associated responses in neurons, vessels and brain extracellular matrix. Acute or prolonged cMet/HGFR inhibition ameliorated neuronal survival and motor recovery. Early elevation of HGF itself in the CSF of TBI patients suggest that this mechanism has translational value in human subjects. Our findings identify cMet/HGFR as a modulator of early neuroinflammation in TBI with translational potential and indicate several RTK families as possible additional targets for TBI treatment.SummaryControlling neuroinflammation in neurotrauma is an important but unachieved goal. This study exploits a moderate TBI model and array-based proteomics to identify cMet as a new inducer of reactive microglia. A small-molecule inhibitor of cMet contains microglial reactivity, reduces neuronal and vascular alterations, limits behavioural disturbances and accelerates recovery.HighlightsMet is activated in microglia upon TBI and drives microglial reactivity.A Met inhibitor reduces motor dysfunction upon TBI and promotes recovery.Blockade of MET prevents the appearance of a reactive microglia.The cMET inhibitor reduces the sub-acute neuronal loss after TBI.

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