scholarly journals Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion NeuronsIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Yong Fu ◽  
Dalian Ding ◽  
Lei Wei ◽  
Haiyan Jiang ◽  
Richard Salvi

Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochleain vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabainin vivovaried among mammalian species. Little is known about the ototoxic effectsin vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabainin vitroand to provide insights that could explain the comparative ototoxic effects of ouabainin vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damagein vitrowas dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways.

2010 ◽  
Vol 130 (12) ◽  
pp. 1316-1323 ◽  
Author(s):  
Haitao Lu ◽  
Xiang Wang ◽  
Wenyan Sun ◽  
Yao Hu ◽  
Shusheng Gong

2021 ◽  
Author(s):  
Muhammad T. Rahman ◽  
Erin M. Bailey ◽  
Benjamin M. Gansemer ◽  
Andrew Pieper ◽  
J. Robert Manak ◽  
...  

AbstractSpiral ganglion neurons (SGNs) relay auditory information from cochlear hair cells to the central nervous system. After hair cells are destroyed by aminoglycoside antibiotics, SGNs gradually die. However, the reasons for this cochlear neurodegeneration are unclear. We used microarray gene expression profiling to assess transcriptomic changes in the spiral ganglia of kanamycin-deafened and age-matched control rats and found that many of the genes upregulated after deafening are associated with immune/inflammatory responses. In support of this, we observed increased numbers of macrophages in the spiral ganglion of deafened rats. We also found, via CD68 immunoreactivity, an increase in activated macrophages after deafening. An increase in CD68-associated nuclei was observed by postnatal day 23, a time before significant SGN degeneration is observed. Finally, we show that the immunosuppressive drugs dexamethasone and ibuprofen, as well as the NAD salvage pathway activator P7C3, provide at least some neuroprotection post-deafening. Ibuprofen and dexamethasone also decreased the degree of macrophage activation. These results suggest that activated macrophages specifically, and perhaps a more general neuroinflammatory response, are actively contributing to SGN degeneration after hair cell loss.


1987 ◽  
Vol 96 (1_suppl) ◽  
pp. 48-50 ◽  
Author(s):  
P. A. Leake ◽  
R. L. Snyder ◽  
C. E. Schreiner

The coadministration of kanamycin (400 mg/kg body weight, s.c.) and aminooxyacetic acid (25 mg/kg body weight, s.c.) results in rapid, total destruction of cochlear hair cells in cats. This drug combination is safer and the time course of hearing losses is less variable than with administration of aminoglycosides alone. Uniform survival of spiral ganglion neurons at 2 and 4 weeks after drug administration suggests a time course similar to that previously observed in neomycin-deafened cats, but more data with longer survival periods are needed to verify these preliminary observations.


Neuroreport ◽  
2010 ◽  
Vol 21 (7) ◽  
pp. 517-521 ◽  
Author(s):  
Athanasia Warnecke ◽  
Verena Scheper ◽  
Ines Buhr ◽  
Gentiana I. Wenzel ◽  
Kirsten Wissel ◽  
...  

2007 ◽  
Vol 503 (6) ◽  
pp. 832-852 ◽  
Author(s):  
Shaheen A. Alam ◽  
Barbara K. Robinson ◽  
Jie Huang ◽  
Steven H. Green

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Na Shen ◽  
Lei Zhou ◽  
Bin Lai ◽  
Shufeng Li

Background. Cochlear implant-based electrical stimulation may be an important reason to induce the residual hearing loss after cochlear implantation. In our previous study, we found that charge-balanced biphasic electrical stimulation inhibited the neurite growth of spiral ganglion neurons (SGNs) and decreased Schwann cell density in vitro. In this study, we want to know whether cochlear implant-based electrical stimulation can induce the change of electrical activity in cultured SGNs. Methods. Spiral ganglion neuron electrical stimulation in vitro model is established using the devices delivering cochlear implant-based electrical stimulation. After 48 h treatment by 50 μA or 100 μA electrical stimulation, the action potential (AP) and voltage depended calcium current (ICa) of SGNs are recorded using whole-cell electrophysiological method. Results. The results show that the ICa of SGNs is decreased significantly in 50 μA and 100 μA electrical stimulation groups. The reversal potential of ICa is nearly +80 mV in control SGN, but the reversal potential decreases to +50 mV in 50 μA and 100 μA electrical stimulation groups. Interestingly, the AP amplitude, the AP latency, and the AP duration of SGNs have no statistically significant differences in all three groups. Conclusion. Our study suggests cochlear implant-based electrical stimulation only significantly inhibit the ICa of cultured SGNs but has no effect on the firing of AP, and the relation of ICa inhibition and SGN damage induced by electrical stimulation and its mechanism needs to be further studied.


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